Tesi: "Bacterial secondary metabolites"

1

Egan, Suhelen Microbiology &amp Immunology UNSW. "Production and regulation of fouling inhibitory compounds by the marine bacterium Pseudoalteromonas tunicata". Awarded by:University of New South Wales. Microbiology and Immunology, 2001. http://handle.unsw.edu.au/1959.4/17838.

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The marine surface-associated bacterium Pseudoaltermonas tunicata, produces a range of compounds that inhibit fouling organisms, including invertebrate larvae, bacteria, algal spores and fungi. In addition to these antifouling compounds P. tunicata cells produce both a yellow and a purple pigment. The aim of this study was to further characterise the antifouling activities, their regulation and relationship with pigmentation, and the ecological significance of P. tunicata and related organisms. It was discovered that the anti-algal compound was extracellular, heat sensitive, polar and between 3 and 10 kDa in size. The anti-fungal compound was found to be the yellow pigment and active against a wide range of fungal and yeast isolates. Chemical analysis suggests that this compound consists of a carbon ring bound to a fatty-acid side chain. Genetic analysis supports the chemical data for the active compound as a mutant in a gene encoding for a long-chain fatty-acid CoA ligase was deficient for anti-fungal activity. To address the regulation of antifouling compounds and their relationship to pigmentation transposon mutagenesis of P. tunicata was performed. Mutants lacking the yellow pigment displayed a reduced ability to inhibit fouling organisms. Further analysis of these mutants identified genes involved with the synthesis and regulation of synthesis of pigment and antifouling compounds. One of these mutants was disrupted in a gene (wmpR) with similarity to the transcriptional regulators ToxR from Vibrio cholerae and CadC from Escherichia coli. Analysis of global protein expression using two-dimensional gel electrophoresis showed that WmpR is essential for the expression of at least fifteen proteins important for the synthesis of fouling inhibitors. The ecological significance of antifouling bacteria was addressed by assessing the antifouling capabilities of a collection of bacteria isolated from different marine surfaces. Overall, isolates from living surfaces displayed more antifouling traits then strains isolated from non-living surfaces. Five dark-pigmented strains originating from the alga Ulva lactuca were further studied. Phylogenetic and phenotypic analysis revealed that they were all members of the genus Pseudoalteromonas and were closely related to P. tunicata. Two strains represented a novel species within the genus and were taxonomically defined as P. ulvae sp. nov.

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Nguyen, Thi Bach Le. "Discovery of active secondary metabolites from Paenibacillus odorifer, a lichen-associated bacterium". Thesis, Rennes 1, 2018. http://www.theses.fr/2018REN1S098/document.

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Les bactéries qui sont des sources prolifiques d'antibiotiques et des fournisseurs importants d’agents pharmaceutiques peuvent produire une grande variété de métabolites. Ainsi, la découverte de métabolites issus bactéries est un nouveau challenge pour les chimistes. Parmi ces sources, les lichens sont admis comme niches intéressantes de nouvelles bactéries et de nouveaux composés bactériens. Par conséquent, les communautés de micro-organismes associées aux lichens sont devenues des sources prometteuses pour la production de composés naturels actifs. Dans cette thèse, nous avons concentré notre travail sur l'isolement des bactéries de Rhizocarpon geogaphicum, l'un des lichens crustacés les plus populaires vivant sur la roche. Parmi les souches isolées, Paenibacillus odorifer a été sélectionnée pour poursuivre les travaux visant à produire des composés actifs. Après des étapes d’optimisation de culture, l’étude des extraits issus des cultures de P. odorifer soit par le bioréacteur soit en Erlenmeyer a permis l’isolement des métabolites : un polysaccharide antioxydant, deux dérivés tert-butylphénoliques cytotoxiques issus de la bioaccumulation et de la biotransformation de précurseurs, d'un nouvel alcaloïde cytotoxique, de deux diols, de deux dérivés de type furfural et quelques autres composés connus. Des hypothèses de biosynthèse ont pu être proposés pour certains composés. La diversité des métabolites isolés de P. odorifer indique que cette espèce possède un grand potentiel de production des composés actifs et est une bactérie utilisatrice de substrats tert-butyl phénoliques
Bacteria which are prolific sources of antibiotics and important suppliers to the pharmaceutical agents can produce a wide variety of metabolites. Thus finding metabolites from the bacterial lineages represented new interests for chemists. Among that, lichens are admitted as a rich source of new bacterial lineages and novel bacterial compounds. Therefore, microorganism communities associated with lichens became significant subjects as great potential for the production of active natural compounds. In this thesis, we focus our work on the isolation of bacterial lineages from the lichen Rhizocarpon geographicum, one of the most popular crustose lichens dwelling on the rock. Among the strains isolated, Paenibacillus odorifer was selected for further work to produce active compounds. After the culture optimization steps, the study of extracts from the P. odorifer cultures either in the bioreactor or in Erlenmeyer flask led to the production of metabolites: an antioxidant polysaccharide, two cytotoxic tert-butylphenol derivatives which came from the bioaccumulation and biotransformation of precursors, a novel and cytotoxic alkaloid compound, two diol compounds, two furfural derivatives and some other known compounds. Putative biosynthetic pathways have been proposed for some compounds. The diversity of metabolites isolated from P. odorifer highlighted that this species possessed a great potential of the production active compounds and were a new case of tert-butyl phenol utilizing bacterium

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3

Liu, Shuai [Verfasser]. "Bioactive Secondary Metabolites from Marine-Derived Fungi and Exploration of Fungal-Bacterial Co-Cultivation / Shuai Liu". Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2016. http://d-nb.info/1122263600/34.

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4

Walmsley, Tara Aisling. "An investigation into the bacterial diversity associated with South African latrunculid sponges that produce bioactive secondary metabolites". Thesis, Rhodes University, 2014. http://hdl.handle.net/10962/d1012943.

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Algoa Bay Latrunculid sponges are well known for their production of cytotoxic pyrroloiminoquinones with speculation that these secondary metabolites may have a microbial origin. This study describes a thorough investigation into the bacterial community associated with Tsitsikamma favus, Tsitsikamma scurra a newly described Latrunculia sp. and a yellow encrusting sponge associated with T. scurra. Molecular and chemical characterisation were used in conjunction with traditional taxonomy in identification of the sponge specimens. The 28S rRNA and COX1 analysis confirmed the traditional taxonomy with T. favus and T. scurra being very closely related. Chemical analysis revealed that T. favus and T. scurra shared the discorhabdins 2,4-debromo-3-dihydrodiscorhabdin C, 7,8-dehydro-3-dihydrodiscorhabdin C and 14-bromo-1-hydroxy-discorhabdin V in common with each other and Tsitsikamma pedunculata indicating that these pyrroloiminoquinones are common to Tsitsikamma sponges in general. The bacterial community associated with T. favus was explored using 16S rRNA molecular techniques including DGGE, clonal libraries of full length 16S rRNA genes, as well as 454 pyrosequencing. DGGE analysis revealed that the bacterial community associated with T. favus appeared to be highly conserved, which was confirmed by both the clone library and 454 pyrosequencing, with the Betaproteobacteria as the most dominant class. Further exploration into T. favus, as well as T. scurra, Latrunculia sp. and the yellow encrusting sponge indicated that the bacterial populations associated with each of these sponge species were conserved and species specific. OTU analysis to the species level revealed that T. favus and T. scurra shared an abundant Spirochaete species in common while the most abundant species in the Latrunculia sp. and the yellow encrusting sponge belonged to the class Betaproteobacteria. The exclusivity of the tsitsikammamines to T. favus precipitated attempts to culture the T. favus associated bacteria, with a focus on the dominant betaproteobacterium as indicated by the 16S rRNA clone library. Actinobacteria associated with the Algoa Bay sponge specimens were also cultured and the actinobacterial isolates were sent for screening against Mycobacterium aurum with two Kocuria kristinae isolates and a Streptomyces albdioflavus isolate showing good antimycobacterial activity.

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5

Gerard, Jeffery M. "Antibiotic secondary metabolites of bacteria isolated from the marine environment". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq25055.pdf.

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6

Hassiotis, Christos N. "Effects of plant secondary metabolites on bacteria and fungi populations". Thesis, University of Reading, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387705.

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7

Sweidan, Alaa. "Antibiofilm activity of lichen secondary metabolites". Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1B017/document.

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Les bactéries buccales n'infectent pas seulement la bouche mais y resident. Elles peuvent également passer dans la voie sanguine et atteindre des organes secondaires. S’il n'est pas traité, le biofilm dentaire peut provoquer une inflammation destructrice dans la cavité buccale, entrainant de graves complications médicales. Dans ce biofilm, Streptococcus gordonii, colonisateur oral primaire, constitue la plate-forme sur laquelle des colonisateurs pathogènes tardifs comme Porphyromonas gingivalis, l'agent causal des maladies parodontales, se lieront. L'objectif de la première partie de la thèse était de déterminer l'activité antibactérienne de onze composés de lichens appartenant à différentes familles chimiques, pour découvrir de nouveaux antibiotiques pouvant combattre ces bactéries buccales. Nous avons montré que trois composés avaient des activités antibactériennes prometteuses. L'acide psoromique enregistrait les CMIs le plus faibles. De nouveaux analogues de butyrolactone ont ensuite été conçus et synthétisés sur la base des composés antibactériens licheniques connus, les acides lichesteriniques, en substituant différents groupes fonctionnels sur le cycle butyrolactone pour améliorer son activité sur S. gordonii et P. gingivalis. Parmi les dérivés, B-12 et B-13 avaient la plus faible CMI où ils se sont révélés être des bactéricides plus forts, 2 à 3 fois plus, que l'antibiotique, doxycycline. B-12 et B-13 étaient également les plus efficaces vis-à-vis de P. gingivalis. La cytotoxicité de ces 2 composés a ensuite été vérifiée contre les cellulaires épithéliales gingivales humaines et les macrophages. Ils ne présentaient pas de toxicité contre les cellules testées. Une étude préliminaire de relation structure-activité a révélé le double rôle important apporté par deux substituants, chaîne alkyle en C5 et groupe carboxyle en C4 positions, dans leur mécanisme d'action. Ceci a été suivi par l'étude de l’activité antibiofilmique de B-12 et B-13 contre les deux souches orales en utilisant un test de cristal violet et microscopie confocale. Les deux dérivés ont montré, à une concentration plus faible, une inhibition maximale de la formation du biofilm, LCMI, de 9.38 μg/mL contre S. gordonii et 1.17 μg/mL contre P. gingivalis. Cependant, lorsque des concentrations sous-inhibitrices de B-12 et B-13 ont été utilisées, nous avons démontré que les deux souches étudiées pouvaient former des biofilms in vitro, accompagné d’une diminution de l'expression des gènes impliqués dans l'adhésion et la formation de biofilm. Pour mieux comprendre les mécanismes d'action des butyrolactones, nous avons étudié la localisation bactérienne du composé B-13 en synthétisant un B-13 marqué au NBD (4-nitro-benzo [1,2,5] oxadiazole) fluorescent conservant son activité antibactérienne. Par microscopie confocale et HPLC, nous avons montré que ce composé se lie à la surface cellulaire de S. gordonii. Ensuite, B-13 induit une rupture de la paroi cellulaire conduisant à la libération des constituants bactériens et par conséquent, à la mort de S. gordonii, une bactérie Gram-positive. L'expression de deux gènes, murA et alr, impliqués dans la synthèse de la paroi cellulaire, a été modifiée en présence de cette butyrolactone. Les bactéries Gram négatives telles que P. gingivalis ont également montré des cellules abimées présentant une rupture de la paroi en présence de B-13, ce qui suggère que cette butyrolactone agit sur des Gram-positives et Gram-négatives avec une plus grande efficacité contre les Gram-négatives. En outre, nous avons également démontré que l'analogue de B-13, B-12, induit une perturbation de la morphologie de P. gingivalis et S. gordonii. Toutes ces études ont démontré que les butyrolactones dérivées de lichen peuvent être proposés comme des composés antibactériens puissants contre les agents pathogènes oraux qui causent des complications médicales graves
The oral bacteria do not only infect the mouth and reside there, but also travel via the blood and reach distant body organs. If left untreated, the dental biofilm that can cause destructive inflammation in the oral cavity may result in serious systemic medical complications. In dental biofilm, Streptococcus gordonii, a primary oral colonizer, constitutes the platform on which late pathogenic colonizers like Porphyromonas gingivalis, the causative agent of periodontal diseases, will bind. The aim of the first study was to determine the antibacterial activity of eleven natural lichen compounds belonging to different chemical families to uncover new antibiotics which can fight against the oral bacteria. Three compounds were shown to have promising antibacterial activities where psoromic acid had the lowest MICs of 11.72 and 5.86 µg/mL against S. gordonii and P. gingivalis, respectively. Novel butyrolactone analogues were then designed and synthesized based on the known lichen antibacterial compounds, lichesterinic acids (B-10 and B-11), by substituting different functional groups on the butyrolactone ring trying to enhance its activity on S. gordonii and P. gingivalis.. Among the derivatives, B-12 and B-13 had the lowest MIC of 9.38 µg/mL where they have shown to be stronger bactericidals, by 2-3 times, than the reference antibiotic, doxycycline. B-12 and B-13 were also the most efficient on P. gingivalis exhibiting MIC of 0.037 and 0.293 µg/mL and MBC of 1.17 and 0.586 µg/mL, respectively. These 2 compounds were then checked for their cytotoxicity against human gingival epithelial cells and macrophages by MTT and LDH assays which confirmed their safety against the tested cell lines. A preliminary study of the structure-activity relationships unveiled the important dual role contributed by two substituents, alkyl chain at C4 and carboxyl group at C5 positions, in their mechanism of action. This was followed by the investigation of B-12 and B-13 for their antibiofilm activity against both oral strains using crystal violet assay and confocal microscopy. Both derivatives displayed a lowest concentration with maximal biofilm inhibition, LCMI, of 9.38 µg/mL against S. gordonii and 1.17 µg/mL against P. gingivalis. However, when sub-inhibitory concentrations of B-12 and B-13 were used, we demonstrated that the two investigated strains were able to form biofilms in vitro. Indeed, this antibiofilm activity decreased as indicated by the expression of the genes implicated in adhesion and biofilm formation. To better understand the mechanism of action of butyrolactones, we have investigated B-13 bacterial localization by synthesizing a fluorescently labeled B-13 with NBD (4-nitro-benzo[1,2,5]oxadiazole) conserving its antibacterial activity. By confocal microscope, we showed that this compound binds to S. gordonii cell surface and this was also demonstrated by HPLC analysis. By adhering to cell surface, B-13 induced cell wall disruption leading to the release of bacterial constituents and consequently, the death of S. gordonii, a Gram-positive bacterium. The expression of two genes, murA and alr, implicated in cell wall synthesis, was modified in the presence of this butyrolactone. Gram-negative bacteria such as P. gingivalis showed also cracked and ruptured cells in the presence of B-13, suggesting that this butyrolactone acts on Gram-positive and Gram-negative strains, but with greater efficacy against the Gram-negatives. Besides, we also demonstrated that the analogue of B-13, B-12, has also induced disruption of P. gingivalis and S. gordonii. All these studies demonstrated that butyrolactones derived from a lichen metabolite can be proposed as potent antibacterial agents against oral pathogens causing serious medical complications

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8

Tesmar, Alexander von [Verfasser], e Rolf [Akademischer Betreuer] Müller. "Investigation of bacterial secondary metabolite pathways / Alexander von Tesmar ; Betreuer: Rolf Müller". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2017. http://d-nb.info/1194371817/34.

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9

Gontang, Erin Ann. "Phylogenetic diversity of gram-positive bacteria and their secondary metabolite genes". Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3324374.

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Thesis (Ph. D.)--University of California, San Diego, 2008.
Title from first page of PDF file (viewed October 3, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.

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10

Matobole, Relebohile Matthew. "Matrix comparison of isolation conditions for secondary metabolite producing marine sponge associated bacteria". University of the Western Cape, 2015. http://hdl.handle.net/11394/4754.

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>Magister Scientiae - MSc
The discovery of novel secondary metabolites has declined significantly in recent years whereas there is a rise in the number of multi-drug resistant pathogens and other types of diseases. The decline in natural product discovery was due to high rediscovery of already known compounds and the costs in developing natural products. As a result pharmaceutical companies lost interest in investing in natural product discovery. However, there is a renewed interest in marine sponge associated microorganisms as a rich and untapped source of secondary metabolites. The objective of this study was to design a matrix to investigate the extent to which the One Strain-Many Compounds (OSMAC) approach applies to a collection of marine sponge isolates harvested from two South African marine sponge samples. Terminal restriction fragment length polymorphisms (T-RFLP) analysis was used to investigate and ascertain the two marine sponges which hosted the highest microbial diversities to be used for further culture-dependent studies. The culture-dependent studies, using 33 media which included liquid enrichment, heat treatments and antibiotic treatments, resulted in 400 sponge isolates from the two marine sponges Isodictya compressa and Higginsia bidentifera. Using antibacterial overlay assays, 31 dereplicated isolates showed antibacterial activity. Bioactivities were also exhibited against E. coli 1699 which is genetically engineered for resistance against 52 antibiotics which implies that some of the bioactive compounds could be novel. The 16S rRNA gene sequences revealed that the microbial phyla isolated from the marine sponges belonged to Actinobacteria, Firmicutes and Proteobacteria (Alphaproteobacteria and Gammaproteobacteria).Thirty isolates were selected for an OSMAC-based matrix study, 17 of which showed noantibacterial activities in preliminary screening. The application of the OSMAC approach using co-culture and 36 culture conditions resulted in 6 isolates showing antibacterial activities, three of which did not show activities in preliminary screening. One of these, a Bacillus pumilus isolated from I. compressa displayed antibacterial activity against 5 indicator strains whereas in preliminary screening it had not shown activity. The results show that marine sponges can host novel microbial species which may produce novel bioactive compounds. The results also confirm that traditional methods employing a single culture condition restricts the expression of some biosynthetic pathways of microorganisms and as a result many metabolites have yet to be identified.

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11

Sun, Min [Verfasser]. "Investigation on the production of secondary metabolites from anoxygenic phototrophic bacteria. / Min Sun". Kiel : Universitätsbibliothek Kiel, 2016. http://d-nb.info/1084634139/34.

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12

Pistorius, Dominik [Verfasser], e Rolf [Akademischer Betreuer] Müller. "Deciphering novel mechanisms of bacterial secondary metabolite biosynthetic pathways / Dominik Pistorius. Betreuer: Rolf Müller". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2011. http://d-nb.info/1051432766/34.

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13

Jungmann, Katrin [Verfasser], e Rolf [Akademischer Betreuer] Müller. "Investigation of bacterial secondary metabolite pathways from Sorangium cellulosum / Katrin Jungmann ; Betreuer: Rolf Müller". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2016. http://d-nb.info/1164443712/34.

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14

Liang, Lanfang. "Investigation of Secondary Metabolites of North Sea Bacteria: Fermentation, Isolation, Structure Elucidation and Bioactivity". Doctoral thesis, [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=96850728X.

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15

Orozco, Rousel Antonio. "Characterization of the Entomopathogenic Bacterium Photorhadus Luminescens Sonorensis, and Bioactivity of its Secondary Metabolites". Thesis, The University of Arizona, 2012. http://hdl.handle.net/10150/228614.

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Photorhabdus are motile Gram-negative bacteria that have a mutualistic association with entomopathogenic Heterorhabditis nematodes. Nematodes vector the bacteria from one insect host to another, while the bacterial symbiont produces toxins and secondary metabolites that kill that the insect host. In this study, we characterize the bacterial symbiont of Heterorhabditis sonorensis, recently discovered in the Sonoran desert. Biochemical and molecular methods including sequence data from five genes: 16s rDNA, gyrB, recA, gltX, dnaN were considered. Evolutionary relationships of this new Photorhabdus subsp. were inferred considering maximum parsimony and Bayesian analyses. We also surveyed for secondary metabolites (SM) produced by this microorganism, considering HPLC and mass spectrometry analyses. SM crude extracts showed activity against the corn ear worm Helicoverpa zea, the root-knot nematode (Meloidogyne incognita), the bacterium Pseudomonas syringae, and the fungus Fusarium oxysporum; and were more toxic that those produced by related species. Results from these studies showed that Photorhabdus l. sonorensis' secondary metabolites have potent antagonistic activity against these plant pathogens.

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Zhu, Liwei. "Identification of secondary metabolite gene clusters of bacteria from south pacific gyre subseafloor sediment". Thesis, University of Rhode Island, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1555704.

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Secondary metabolites are organic compounds that are not directly involved in the key processes (growth, reproduction and development) of an organism. They are commonly targeted in pharmaceutical science for drug discovery. Secondary metabolites that have been used in drug discovery have been derived from plants, invertebrates and microbes. Microbes, bacteria in particular, have contributed greatly and will continue to play an important role in new drug discovery. Among the bacteria from all environments, marine bacteria are a vast reservoir for many potential useful bioactive compounds. Recent studies using marine bacteria for pharmaceutical use mainly focused on the bacteria collected from near-shore sediments. However, bacteria from deep-sea sediments remain unexplored. The South Pacific Gyre (SPG) is the most oligotrophic region of the world ocean. Due to the low surface productivity and distance from land, sediments below the gyre accumulate very slowly and are characterized by very low organic carbon content and relatively high dissolved oxygen concentrations. Sediments from South Pacific Gyre were found to host a living microbial community that, compared to other marine sediments, contains very low microbial biomass and very low metabolic activity. Thus, the goal of this study is to: (1) document the cultivatable bacterial diversity; and (2) explore the pharmaceutical potential of deep-sea bacteria from South Pacific Gyre sediment. To address this, bacteria were isolated in pure culture from sediments from seven sites of the Integrated Ocean Drilling Program (IODP) Expedition 329 in the South Pacific Gyre. 16S rRNA genes from 81 bacterial isolates throughout six SPG sites (U1366, U1367, U1368, U1369, U1370 and U1371) were sequenced for phylogenetic analysis using the RDP (Ribosomal Database Project). 16S rRNA genes were amplified with bacterial primers that have been proven to amplify bacterial sequences well (27F, 1392R). Whole genomes from nine Rhodococcus isolates (with two duplicates) throughout four SPG sites (U1366, U1367, U1370 and U1371) were sequenced for secondary metabolites gene clusters discovery. By using antiSMASH (antibiotics & Secondary Metabolite Analysis SHell), secondary metabolite biosynthesis gene clusters in the bacterial genome were identified, annotated and analyzed. Of the 81 16S rRNA gene clone libraries constructed, most of the clones (63%) affiliated with the genus Bacillus, 35.8% were affiliated with the genus Rhodococcus and one clone was identified as a Corynebacterium. The phylogenetic tree further indicated that all the Rhodococci were identified as Rhodococcus erythropolis. By using antiSMASH to look for the secondary metabolites gene clusters from the Rhodococcus genomes, many gene clusters, most of which were NPRS and PKS, were found in the genomes. This study suggests that deep-sea sediments harbor bacteria with the potential to produce pharmaceutically important secondary metabolites.

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Nicácio, Karen de Jesus. "Isolamento e identificação de metabólitos produzidos por linhagens de microrganismos do ambiente marinho". Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/75/75133/tde-29092017-174924/.

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A investigação de produtos naturais tem sido cada vez mais direcionada para o estudo de microrganismos, com destaque para aqueles do ambiente marinho. Neste trabalho foram estudadas linhagens bacterianas isoladas de tecidos da esponja Arenosclera brasiliensis, como parte de um estudo que tinha o objetivo de encontrar novas moléculas bioativas. O cultivo da linhagem bacteriana Pseudovibrio denitrificans Ab134 permitiu o isolamento e identificação de três compostos derivados de dibromotirosina, a fistularina-3 (26), o ácido verongidoico (27) e a 11-hidroxiaerotionina (28). Outros cinco compostos derivados de dibromotirosina foram detectados, em frações ainda impuras, através de análises por CLUE-qTOF e tiveram suas estruturas propostas de acordo com os íons de fragmentação observados no espectro de EMAR: aerotionina (29), um éster do ácido purpurocerático B (30), purealidina L (31) e aplisinamisina II (32). Este é o primeiro relato da produção dos derivados de dibromotirosina a partir de uma linhagem bacteriana e representa um forte indício de que tais compostos, comumente isolados de esponjas, são na verdade produzidos pela microbiota associada destes animais. O cultivo da linhagem fúngica Biatriospora sp. permitiu o isolamento e identificação de nove compostos diterpênicos da classe das fomactinas, sendo seis deles inéditos. As fomactinas são conhecidas por apresentarem potente atividade como inibidoras de receptores do PAF. As fomactinas S, P, U e I apresentaram bons resultados na inibição da ligação do PAF aos seus receptores. As fomactinas S e P foram também avaliadas em ensaio de re-população tumoral pós irradiação e foram capazes de inibir o fenômeno de re-população em concentração molar equivalente a antagonistas comerciais. Tal resultado sugere que a associação da radioterapia com antagonistas do PAF-R pode ser uma nova e eficiente alternativa terapêutica para inibição do crescimento de tumores.
Research on natural products is increasingly focusing on the study of microorganisms, especially those from the marine environment. In the present investigation, bacterial strains isolated from tissues of the sponge Arenosclera brasiliensis were studied in order to find new bioactive molecules. Cultivation of the bacterial strain P. denitrificans allowed the isolation and identification of three dibromotyrosine-derived compounds: fistularin-3 (26), verongidoic acid (27) and 11-hydroxyaerothionin (28). Another five dibromotyrosine-derived compounds were detected in still impure fractions by UPLC-qTOF analysis and had their structures proposed according to the fragmentation ions observed in the HRMS spectrum: aerothionin (29), the methyl ester of purpuroceric acid B (30), purealidin L (31) and aplisinamysin II (32). This is the first report of the production of dibromotyrosine derivatives by a bacterial strain and represents a strong indication that such compounds, commonly isolated from sponges, are actually produced by the associated microbiota of these animals. Cultivation of the fungal strain Biatriospora sp. allowed the isolation and identification of nine fomactin diterpenes, six of wich are new. Fomactins are known as inhibitors of PAF receptors. Fomactins S, P, U and I have shown good results in inhibiting the binding of PAF to their receptors. The fomatins S and P were also evaluated in the post-irradiation tumor re-population assay and were able to inhibit the re-population phenomenon at micromolar concentration equivalent to commercial antagonists. Such a result suggests that the association of radiotherapy with PAF-R antagonists may be a new and efficient therapeutic alternative in tumors.

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18

Mincer, Tracy John. "Phylogenetic and ecological investigations of secondary metabolite producing marine bacteria and their potential for biotechnology /". Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2004. http://wwwlib.umi.com/cr/ucsd/fullcit?p3142452.

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19

Christianson, Carl Victor. "Understanding The Biosynthesis And Utilization Of Non-Proteinogenic Amino Acids For The Production Of Secondary Metabolites In Bacteria". Thesis, Boston College, 2008. http://hdl.handle.net/2345/967.

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Abstract (sommario):

Thesis advisor: Steven D. Bruner
Bacteria utilize complex enzymatic machinery to create diverse secondary metabolites. The architectural complexities of these small molecules are enhanced by nature’s ability to synthesize non-proteinogenic amino acids for incorporation into these scaffolds. Many of these natural products are utilized as therapeutic agents, and it would be advantageous to understand how the bacteria create various non-natural amino acid building blocks. With a greater understanding of these systems, engineering could be used to create libraries of potentially useful natural product analogs. The tyrosine aminomutase SgTAM from the soil bacteria Streptomyces globisporus catalyzes the formation of tyrosine to generate (S)-B-tyrosine. The precise mechanistic role of MIO in this novel family of aminomutases has not been established. We report the first X-ray crystal--> structure of an MIO based aminomutase and confirm the structural homology of SgTAM to ammonia lyases. Further work with mechanistic inhibitors provide structural evidence of the mechanism by which MIO dependent enzymes operate. We have also investigated LnmQ, an adenylation domain in the biosynthetic pathway of leinamycin. Leinamycin is an antitumor antibiotic that was isolated from soil samples in 1989. LnmQ is responsible for the specific recognition of D-alanine and subsequent activation as an aminoacyl adenylate species. We have cloned the gene into a DNA vector and expressed it in E. coli. Upon purification of the protein, crystallization conditions have been tested. Synthesis of an inhibitor that mimics the aminoacyl adenylate product catalyzed by LnmQ has been completed. Crystallization with this--> inhibitor will provide better quality crystals and a catalytically informative co-complex
Thesis (PhD) — Boston College, 2008
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

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Schieferdecker, Sebastian [Verfasser], Markus [Akademischer Betreuer] Nett, Dirk [Akademischer Betreuer] Hoffmeister e Manuela [Akademischer Betreuer] Tosin. "Secondary metabolites from predatory bacteria : isolation, structure elucidation and bioactivity / Sebastian Schieferdecker. Gutachter: Markus Nett ; Dirk Hoffmeister ; Manuela Tosin". Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2015. http://d-nb.info/1076038476/34.

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21

Conway, Crystal A. "Study of Secondary Metabolite Gene Expression in Marine Microbial Co-Cultures Using Quantitative Real-Time PCR". NSUWorks, 2010. http://nsuworks.nova.edu/occ_stuetd/222.

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Abstract (sommario):

Interactions among microbial organisms often cannot be observed directly, but they can be inferred genetically using new molecular techniques. The analysis of secondary metabolite gene expression produced by co-cultured marine microbial species allows us to see how these organisms interact with one another when kept in the same environment. Co-cultures of three different strains of marine bacteria, P. aeruginosa PAO1, Roseobacter denitrificans OCH114, and Salinispora arenicola CNS-205 were grown in a laboratory setting, and using the Real-Time qPCR method gene expression levels of two different secondary metabolite producing genes from each organism was accessed across three time points. P. aeruginosa PAO1’s secondary metabolite genes RdhA and PhzH stayed repressed through all co-cultures and time points in this study, and Roseobacter denitrificans OCH-114’s secondary metabolite genes metallo-beta-lactamase and DMSP lyase were up-regulated after the 30 minute time point in the P. aeruginosa-R. denitrificans co-culture and at the 0 minute time point in the R. denitrificans-S. arenicola co-culture.

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22

Zhang, Jianhai. "Synthetic Biology of Antibiotic Production : Assembly and Re-factoring of Secondary Metabolite Biosynthesis Gene Clusters for Heterologous Expression in Genetically Engineered Bacterial Host". Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for bioteknologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-27325.

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Abstract (sommario):

The issues in new antibiotic discovery are pressing, because the frequent re-discovery of antibiotic scaffolds leads to few novel antibiotics discovered, besides, with the widespread use of antibacterial agents, multi-resistant pathogens are emerging, which poses more huge challenge in antibiotic discovery. However, next generation sequencing technology and bioinformatics have revealed that many secondary metabolite biosynthesis gene clusters possess the potential of producing new bioactive secondary metabolites (BSMs), which were ignored previously. Among the microorganisms, actinomycetes species are the best sources for those gene clusters. Synthetic biology is the enabling technology to activate those silent gene clusters, which aims to engineer organisms for expected applications with combination of various biotechnologies. The project employs the reciprocal regulation system between jadomycin (Jd) and chloramphenicol (Cm) in S. venezuelae: JadR1 activates Jd synthesis while represses Cm synthesis with ethanol shock. This system can be used to rationally engineer S. venezuelaee for heterologous production of BSMs with re-factored gene clusters containing appropriate control elements: deletion of the jadR1 gene shall lead to down-regulation of Jd production, simultaneously induce overproduction of Cm due to the relieved repression of the Cm structural genes’ promoters. Besides, the cml gene cluster should be completely deleted to avoid interfering with the introduced gene cluster. The appropriate control element is an inducible promoter screened out with GUS assay among cmlFp, cmlIp, cmlXp, jadJp. The inducible promoter would be used to construct an inducible system for industrial scale production of BSMs, because constitutive heterologous expression of BSMs is harmful for producing hosts.The jadR1- cml- mutants were successfully generated with Gibson Assembly, transconjugation, double crossover and replica plating. The gene cluster MP112-09-Lac was cloned with native promoter and ermE* respectively and transconjugated to jadR1- cml- mutant, however, cloing of MPS05-B41-Lin was hindered by wrong PCR amplification. The four promoters were tested with GUS assay, based on MYM medium and cmlF is speculated to be the most desirable inducible promoter.

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23

Okanya, Patrick W. S. [Verfasser], e Rolf [Akademischer Betreuer] Müller. "Isolation and structure elucidation of secondary metabolites from the gliding bacteria Ohtaekwangia kribbensis and Hyalangium minutum / Patrick W. S. Okanya. Betreuer: Rolf Müller". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2012. http://d-nb.info/1063210380/34.

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24

Duell, Elke Regina [Verfasser], Tobias A. M. [Akademischer Betreuer] Gulder, Tobias A. M. [Gutachter] Gulder e Michael [Gutachter] Groll. "Investigations into (cyano-)bacterial secondary metabolite biosynthesis in heterologous expression systems / Elke Regina Duell ; Gutachter: Tobias A. M. Gulder, Michael Groll ; Betreuer: Tobias A. M. Gulder". München : Universitätsbibliothek der TU München, 2019. http://d-nb.info/1205069364/34.

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25

Santos, Viviane Colombari Pedrazzini dos. "Atividade antibacteriana de Burkholderia spp. endofíticas e da rizosfera de cana-de-açúcar". Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/11/11137/tde-10082010-150035/.

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A cultura de cana-de-açúcar ocupa posição de destaque nos cenários nacional e internacional devido principalmente a produção de etanol como fonte de energia renovável e menos nociva ao ambiente. Entretanto um dos obstáculos à produtividade é a ocorrência de várias doenças dentre elas a escaldadura das folhas causada por Xanthomonas albilineans. Bactérias endofíticas e rizosféricas pertencentes ao gênero Burkholderia tem sido isoladas com alta frequência em diferentes culturas como, por exemplo, a cana-de-açúcar. Nas últimas décadas, estas bactérias têm recebido especial atenção devido ao seu potencial como promotoras de crescimento vegetal, como agentes de biorremediação, mas muito pouco é explorado quanto ao potencial biotecnológico dessas bactérias como agentes de biocontrole de doenças. Visto que essas bactérias vivem em um ambiente altamente competitivo e sujeito a flutuações ambientais, representam uma fonte altamente significativa de metabólitos secundários bioativos, como as bacteriocinas sintetizadas ribossomicamente e outros peptídeos não ribossomais. Portanto, os objetivos principais deste trabalho foram determinar a frequência de linhagens de Burkholderia spp. endofíticas e da rizosfera de cana-deaçúcar capazes de produzir bacteriocinas e outros metabólitos secundários e por meio de mutagênese aleatória por transposon, identificar genes associados a produção desses metabólitos. Os resultados de caracterização permitiram concluir que as bactérias endofíticas e rizosféricas pertencentes ao gênero Burkholderia avaliadas apresentaram grande potencial em produzir metabólitos com atividade antibacteriana in vitro; sendo capazes de controlar X. albilineans importante patógeno da cultura de cana-de-açúcar. Para uma das linhagens foi obtida uma biblioteca de mutantes, a qual foi parcialmente caracterizada quanto à alteração da atividade antibacteriana. Foram identificados doze mutantes que apresentaram perda da atividade antibacteriana. A análise das sequências flanqueadoras do transposon para os doze mutantes permitiu a identificação de genes associados a produção de bacteriocinas, a regulação da expressão gênica, a enzimas possivelmente associadas ao metabolismo secundário, ao metabolismo geral da célula e a proteínas hipotéticas. A identificação e clonagem de tais genes permitirão uma maior compreensão da produção desses compostos e futuras aplicações biotecnológicas.
The sugarcane crop has an important role in international and national scenery mainly because the ethanol production as a sustainable energy source and less harmful to the environment. However one of the obstacles to the productivity is the occurrence of several diseases among them leaf scald caused by Xanthomonas albilineans. Endophytic and rhizospheric bacteria that belong to the Burkholderia genus have been isolated in high frequency in different cultures, such as sugarcane. In the last decades, these bacteria have been receiving attention due their potential as plant growth promoters, bioremediation agents. However, the biotechnological potential of these bacteria as agents of diseases biocontrol is very poorly evaluated. Since these bacteria live in a highly competitive environment and subject to environmental fluctuations, they may represent a highly significant source of bioactive secondary metabolites, as ribosomal synthesized bacteriocins and other nonribosomal peptides. Therefore, the main aim of this work was to determine the frequency of bacteriocin and secondary metabolites production by endophytic and rhizospheric isolates of Burkholderia spp. from sugarcane. Also, the genes associated to synthesis of these metabolites were identified by random mutagenesis based on Tn5 transposon. The results showed that endophytic and rhizospheric Burkholderia spp. present in vitro potential to production of metabolites with antibacterial activity; being inhibited X. albilineans, an important pathogen of sugarcane crops. For one of the Burkholderia strain it was obtained a mutant library, which was partially characterized according to antibacterial activity. Twelve mutants that showed the loss of antibacterial activity were identified and further evaluated. Also, the analysis of the transposon flanking sequences for these mutants indicated that genes associated to the bacteriocin production, regulation of gene expression, enzymes possibly associated to the secondary metabolism, general metabolism of the cell and hypothetical proteins are related to loss of inhibition ability. The identification and cloning of such genes will allow a better understanding of the production of theses compounds and further biotechnological applications.

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Abdel, Rahim Hamdi Mohamed Desoky [Verfasser], e Barbara [Akademischer Betreuer] Schulz. "Suhagcines I and II, Unusual Nucleosides, Diketopiperazines and Further New Secondary Metabolites from Fungal Strains, Terrestrial and Marine Bacteria / Hamdi Mohamed Desoky Abdel Rahim ; Betreuer: Barbara Schulz". Braunschweig : Technische Universität Braunschweig, 2011. http://d-nb.info/1175825239/34.

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27

Nair, Vimal [Verfasser], Hartmut [Akademischer Betreuer] Laatsch, Ulf [Akademischer Betreuer] Diederichsen e Birger [Akademischer Betreuer] Dittrich. "Indole Alkaloids as Potential Leads in Drug Discovery and Further Secondary Metabolites from Terrestrial and Marine Bacteria / Vimal Nair. Gutachter: Ulf Diederichsen ; Ulf Diederichsen ; Birger Dittrich. Betreuer: Hartmut Laatsch". Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2012. http://d-nb.info/1043779175/34.

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28

Silva, Caroline Souza Pamplona da. "Caracterização molecular de cianobactérias isoladas de ecossistema manguezal do Estado de São Paulo e identificação de produtos naturais". Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/11/11138/tde-02082010-165249/.

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Abstract (sommario):

O gene de RNAr 16S tem sido amplamente utilizado na inferência filogenética de organismos procariotos, entretanto, sequências desse gene de cianobactérias isoladas de manguezais brasileiros são inexistentes. Neste estudo, 42 sequências inéditas do gene de RNAr 16S de cianobactérias isoladas de manguezais brasileiros foram geradas. Na análise BLAST as sequências apresentaram similaridades variando de 91 a 99% com outras sequências conhecidas de cianobactérias depositadas no GenBank. Na análise filogenética do gene de RNAr 16S várias sequências do gênero Chlorogloea ficaram agrupadas com sequências do gênero Synechococcus e algumas sequências de Nostoc ficaram mais próximas de sequências de Nodularia. As sequências de Leptolyngbya agruparam-se separadas das típicas de Leptolyngbya. Esses resultados corroboram com outros estudos, os quais mostraram que o filo Cyanobacteria necessita de revisão taxonômica. Na avaliação do potencial de produção de substâncias bioativas de 44 isolados de manguezais utilizando a técnica de PCR e dois conjuntos de oligonucleotídeos iniciadores degenerados específicos para sequências gênicas codificantes de peptídeo sintetase não ribossômica (NRPS) e policetídeo sintase (PKS) modular, 10 linhagens apresentaram resultado positivo para presença de NRPS e todos os isolados apresentaram resultado positivo para PKS. Na tentativa de atribuir função a esses genes e posteriormente explorar as potencialidades das linhagens, um produto da PCR de NRPS e 19 de PKS foram sequenciados, as sequências obtidas foram traduzidas para aminoácidos e utilizadas na construção de árvores filogenéticas. A análise filogenética da sequência de aminoácido do domínio de adenilação da NRPS indicou uma possível síntese de sideróforo pela linhagem Phormidium CENA135. Extratos extracelulares dessa linhagem analisados por Q-TOF/MS e RMN indicaram a produção de um sideróforo anfifílico com massa molecular e estrutura similar ao sideróforo synechobactina A. As sequências de aminoácidos do domínio da cetossintase de PKS das 19 linhagens mostraram relações filogenéticas com várias PKSs de linhagens conhecidas por produzirem substâncias, tais como sideróforo, algicida, microginina, oscilaginina B, hectoclorina e scytonemina. No teste da atividade antimicrobiana contra micro-organismos patogênicos dos extratos intra e extracelulares das 44 linhagens, 17 delas inibiram o crescimento de vários dos micro-organismos testados. Os extratos ativos foram analisados por Q-TOF/MS e 34 substâncias putativas conhecidas foram identificadas, tais como fungicidas, inibidores de proteases, antimaláricos e outras de funções desconhecidas. O teste imunológico ELISA específico para detecção da hepatotoxina microcistina (MC) apresentou resultado positivo para 16 das 23 linhagens testadas. Fragmentos de sequências do gene mcyA envolvido na síntese de MC foram amplificados por PCR em cinco linhagens (Synechococcus CENA136, Phormidium CENA135, Chlorogloea CENA142, Chlorogloea CENA146 e Nostoc CENA160), inclusive em dois gêneros sem registro de produção dessa toxina (Synechococcus e Chlorogloea). O teste ELISA específico para detecção da neurotoxina saxitoxina (SXT) apresentou resultado positivo para três linhagens. Entretanto, a análise em Q-TOF/MS e FT-ICR/MS de 15 linhagens, inclusive das que apresentaram resultado positivo no ELISA, não confirmaram a produção de saxitoxinas.
The 16S rRNA gene has been widely used in phylogenetic inference of prokaryotic organisms, however, sequences of this gene of cyanobacteria isolated from Brazilian mangroves are absent. In this study, 42 newly sequences of 16S rRNA gene of cyanobacteria isolated from Brazilian mangroves were generated. BLAST analysis of the sequences showed similarities ranging from 91-99% with other known cyanobacterial sequences deposited in GenBank. Phylogenetic analysis of several 16S rRNA sequences from the genus Chlorogloea were clustered with sequences from the genus Synechococcus and some sequences of Nostoc were closer to sequences of Nodularia. The Leptolyngbya sequences clustered separated from those of typical Leptolyngbya. These results corroborate with other studies which showed that the phylum Cyanobacteria need taxonomic revision. In assessing the potential of bioactive compounds production of 44 mangrove isolates using PCR technique and two sets of degenerated primers specific for gene sequences encoding non-ribosomal peptide synthetase (NRPS) and modular polyketide synthase (PKS), 10 strains showed positive results for the presence of NRPS and all isolates were positive for PKS. In an attempt to assign function to these genes and further explore the potential of the strains, a PCR product of NRPS and 19 PKS were sequenced and the sequences obtained were translated into amino acids and used to construct phylogenetic trees. Phylogenetic analysis of amino acid sequence of the NRPS adenylation domain indicated a possible synthesis of siderophore by the Phormidium strain CENA135. Extracellular extracts of this strain analyzed by Q-TOF/MS and NMR indicated the production of an amphiphilic siderophore with molecular mass and structure similar to the siderophore synechobactin A. The amino acid sequences of the PKS ketosynthase domain of 19 strains showed phylogenetic relationships with several PKSs of strains known to produce compounds such as siderophore, algicide, microginin, oscillaginin B, hectochlorin and scytonemin. In the antimicrobial activity test against pathogenic microorganisms of the intra- and extracellular extracts of 44 strains, 17 of them inhibited the growth of various microorganisms tested. The active extracts were analyzed by Q-TOF/MS and 34 putative known substances were identified such as fungicides, protease inhibitors, antimalarials, and others of unknown function. The immunological test ELISA specific for detection of the hepatotoxin microcystin (MC) was positive for 16 of the 23 strains tested. Sequence fragments mcyA gene involved in the synthesis of MC were amplified by PCR in five strains (Synechococcus CENA136, Phormidium CENA135, Chlorogloea CENA142, Chlorogloea CENA146 and Nostoc CENA160), including two genera with no record of production of this toxin (Synechococcus and Chlorogloea). Specific ELISA test for detection of the neurotoxin saxitoxin (SXT) showed positive results for three strains. However, analysis by Q-TOF/MS and FT-ICR/MS of 15 strains, including those that showed positive ELISA results, did not confirm the saxitoxin production.

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Tabares, Paula [Verfasser], e Ute [Akademischer Betreuer] Hentschel. "Antimicrobial, anti-protease and immunomodulatory activities of secondary metabolites from Caribbean sponges and their associated bacteria = Sekundärmetabolite mit antimikrobiellen, Protease-hemmenden und immunmodulatorischen Aktivitäten aus karibischen Schwämmen und assoziierten Bakterien / Paula Tabares. Betreuer: Ute Hentschel". Würzburg : Universitätsbibliothek der Universität Würzburg, 2012. http://d-nb.info/1018612874/34.

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Bhedi, Chinmayee D. "Quorum Sensing Signals Produced by Heterotrophic Bacteria in Black Band Disease (BBD) of Corals and Their Potential Role in BBD Pathogenesis". FIU Digital Commons, 2017. http://digitalcommons.fiu.edu/etd/3367.

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Abstract (sommario):

Black band disease (BBD) of corals is a temperature dependent, highly virulent, polymicrobial disease affecting reef-building corals globally. The microbial consortium of BBD is primarily comprised of functional physiological groups that include photosynthetic cyanobacteria, sulfate reducers, sulfide oxidizers and a vast repertoire of heterotrophic bacteria. Quorum sensing (QS), the cell-density dependent communication phenomenon in bacteria, is known to induce expression of genes for a variety of virulence factors in diseases worldwide. Microbes capable of QS release signals such as acyl homoserine lactones (AHLs) and autoinducer-2 (AI-2), which coordinate microbial interaction. The focus of the present study was to investigate the presence and potential role of QS in BBD pathogenicity, utilizing culture dependent and independent methodologies. Isolates across coral health states including BBD, were screened for production of QS signals, and AHL and AI-2 production capabilities were analyzed via LC-MS/MS. The effect of temperature on AHLs was also examined. Additionally, antimicrobial production capabilities of isolates were tested. BBD metagenomes were utilized to screen for sequences related to QS, antimicrobial synthesis, and antimicrobial resistance genes. BBD isolates represented a significantly higher proportion of isolates capable of producing QS signals in comparison to healthy coral isolates. Several AHLs produced by coral derived bacterial cultures were identified, and three AHLs, specifically 3OHC4, 3OHC5 and 3OHC6, showed a significant increase in production at an elevated temperature of 30 °C, which correlates with increased BBD incidence on reefs with increasing water temperature. Most of the BBD cultured isolates were identified as vibrios. Several sequences related to QS, antimicrobial synthesis and resistance genes were detected in the BBD metagenomes. Based on the findings of this study, a model for potential microbial interactions amongst BBD heterotrophs, centered around QS, is proposed. Taken together, the findings from this study provide a clearer understanding of the potential role of QS in BBD, and serve as the basis for further studies aimed at elucidating the pathogenesis of an intricate coral disease.

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Schuhmann, Imelda. "Aufbau einer HPLC-UV-ESI-MS-MS-Datenbank und ihre Anwendung im Screening arktischer und antarktischer Meeresbakterien". Doctoral thesis, [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=977037568.

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32

Rasamiravaka, Tsiry. "Inhibition du mécanisme de quorum sensing et de la formation de biofilm chez Pseudomonas aerugionsa par des composés bioactifs de Dalbergia trichocarpa (Fabaceae)". Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209303.

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Abstract (sommario):

Depuis quelques décennies, les bactéries pathogènes multi-résistantes aux antibiotiques sont de plus en plus répandues dans le monde. Cette situation a suscité le besoin et l'intérêt de trouver des médicaments antibactériens avec de nouvelles cibles potentiels. La découverte des systèmes de communication de type quorum sensing (QS) régulant la virulence bactérienne représente une des cibles privilégiées pour contrôler les bactéries pathogènes autrement qu’en interférant avec leur croissance bactérienne. Dans l’écosystème naturel, un grand nombre d'organismes (Eucaryotes et Procaryotes) co-existent en synthétisant chacun de leur côté des métabolites secondaires. Les plantes, étant en permanence en contact avec des bactéries, synthétisent des métabolites secondaires capables d’inhiber l’expression des gènes de virulence chez les bactéries sans pour autant affecter ni leur croissance ni leur viabilité. Notre objectif a été de contribuer à la valorisation de la biodiversité malgache en identifiant des plantes et en y isolant les composés actifs présentant une capacité à perturber le mécanisme de QS chez P. aeruginosa PAO1, une bactérie pathogène opportuniste de l’homme, des animaux et des plantes. Dans ce but, nous avons tout d’abord réalisé un criblage d’activité anti-QS de différents flavonoïdes commerciaux. De ce criblage, la narigenine et la naringine ont été sélectionnées pour être les molécules de contrôle positif et négatif des tests d’activité anti-QS, respectivement. Par la suite, 4 espèces de Dalbergia endémique de Madagascar ont fait l’objet de criblage pour leur activité anti-QS. Ce travail a fait ressortir l’activité anti-QS très intéressante de l’écorce de D. trichocarpa à partir de laquelle nous avons isolée le composé actif nommé la coumarate de l’aldéhyde-oléanolique (OALC). Le contrôle naringénine et l’OALC ne présente aucun effets inhibiteurs sur la croissance bactérienne de P. aeruginosa PAO1 et sur l’expression du gène QS-indépendant aceA suggérant une activité d’inhibition spécifiquement liée au QS. Cependant, ces deux molécules présentent des spectres d’inhibition différente. En effet, les deux molécules diffèrent dans le sens que la naringenine n’inhibe pas l’expression du gène gacA et la motilité de type twitching contrairement à l’OALC. Ces résultats suggèrent que l’OALC et la naringénine représente des candidats potentiels pour des investigations in vivo quant à leur effet anti-QS et anti-biofilm sur des modèles infectieux d’organismes supérieurs. Par ailleurs, ils démontrent la richesse des plantes malgaches comme sources de nouvelles molécules anti-virulence ainsi que l’importance de telle investigation afin de renforcer notre arsenal thérapeutique en composé antibactérienne dans la lutte continuelle contre les bactéries pathogènes/Since few decades, multidrug resistant bacteria spread all over the world. This situation gives rise to the need and interest in finding antibacterial drugs with novel potent target. Discovery of communication system termed Quorum Sensing (QS) which regulate bacterial virulence factor represent privileged target in another way than interfering with bacterial growth. In natural ecosystem, many organisms (Eukaryotes and Prokaryotes) produce secondary metabolites. As plants are permanently in contact with bacteria, they have synthetized secondary metabolites which inhibit bacterial virulence gene expression without affecting bacterial viability. Our goal was to contribute to the valorization of Malagasy biodiversity and specifically to identify plants and isolate bioactive compound presenting ability to disrupt QS mechanism in P. aeruginosa, opportunistic pathogen bacteria in plants, animals and human. In this purpose, screening of commercial available flavonoids has been firstly carried out. From this screening, naringenin and naringin have been selected to be used as positive and negative QS inhibitor controls, respectively. Subsequently, Four Malagasy endemic Dalbergia species have been screened for their anti-QS activity. This work pointed out the interesting anti-QS activity of D. trichocarpa bark extract which led to the isolation of oleanolic aldehyde coumarate (OALC) as one major bioactive compound. At the concentration tested, naringenin and OALC did not affect P. aeruginosa PAO1 viability and didn’t reduce QS-independent aceA gene expression suggesting a specific anti-QS activity. However, these two compounds present different inhibition spectrum. Indeed, naringenin didn’t inhibit gacA gene expression and twitching motility contrarily to OALC. These results suggest that OALC and naringenin represent potent candidates for in vivo investigations in their anti-QS and anti-biofilm activity onto eukaryotes infectious model. Besides, this finding demonstrated the potent source for novel anti-virulence compounds of Malagasy flora and the importance of this kind of research to strengthen our antimicrobial therapeutic arsenal with the ongoing struggle against bacterial infection.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished

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33

Rajaonson, Sanda. "Inhibition of virulence gene expression in Rhodococcus fascians and Pseudomonas aeruginosa by flavonoïds isolated from the genera Dalbergia and Combretum". Doctoral thesis, Universite Libre de Bruxelles, 2011. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209789.

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Plants are continuously confronted with a multitude attack either abiotic but also biotic in nature. Interestingly, despite the abundance of bacteria that plant has to face, only few are able to induce death or disease in the host plant. It is therefore likely that, in addition to secondary metabolites with antimicrobial properties, plants also synthesize secondary metabolites which are able to inhibit the expression of virulence genes in bacteria without affecting either growth or viability, which allows plants to host willingly or not bacterial populations. This work focuses on the identification of such metabolites in Malagasy plants (genera Dalbergia and Combretum) and the demonstration of their inhibitory effect on the expression of virulence genes in two different pathosystems: Rhodococcus fascians (a phytopathogen) and Pseudomonas aeruginosa (an opportunistic pathogen). Thus, two metabolites were isolated using a combination of chromatographic techniques coupled with tests that evaluate the expression of certain genes involved in the virulence mechanisms of these bacteria. The first is a new prenylated isoflavanone, named perbergin, isolated from the bark extract of D. pervillei. It was shown that the perbergin target attR gene expression, encoding a LysR-type transcriptional regulator that plays a key role in regulating the expression of virulence genes of R. fascians and the transition from an epiphytic to a pathogenic lifestyle. Therefore, we have also shown that the expression of all virulence genes known to date in R. fascians is also affected while the expression of genes involved in epiphytic fitness of the bacteria is not altered. In addition, the application of perbergin at the time of infection of plants susceptible to R. fascians shows that this molecule reduces in vivo the virulence of R. fascians, highlighting the potential of perbergin as an anti-infective agent. The second is a flavonoid known as catechin, isolated from the bark extract of C. albiflorum. Catechin significantly inhibits the expression of genes that regulate the mechanism of quorum sensing in P. aeruginosa such as lasI, LasR, rhlI and rhlR but also lasB and rhlA which expression depends on quorum sensing. Therefore, the production of virulence factors such as pyocyanin and elastase is significantly affected. Because of the limited number of our arsenal of antibiotics and their increasing ineffectiveness, the identification of these compounds create a path to an alternative in the fight against pathogenic bacteria and multidrug resistance of pathogenic bacteria to antibiotics. Our results also demonstrate the richness of Malagasy plants as (re)sources of new therapeutic molecules and the importance of widening the range of bacterial targets to be investigated to develop new strategies to fight within the endless war that we are waging against bacteria pathogens.

Les plantes sont continuellement confrontées à une multitude d’attaques qu’elles soient de nature abiotique ou surtout biotique. Il est intéressant de noter que malgré la multitude de bactéries auxquelles les plantes doivent faire face, seules quelques unes sont capables d’induire la mort ou une maladie chez la plante hôte. Il est dès lors fort probable que, outre les métabolites secondaires ayant des propriétés antimicrobiennes, les plantes synthétisent également des métabolites secondaires capables d’inhiber l’expression des gènes de virulence chez les bactéries sans toutefois affecter ni leur croissance ni leur viabilité, ce qui permet aux plantes de contenir les populations bactériennes qu’elles hébergent de gré ou de force. Ce travail porte sur l’identification de ce type de métabolites dans des plantes malgaches (genres Dalbergia et Combretum) et la démonstration de leurs effets inhibiteurs sur l’expression de gènes de virulence chez deux pathosystèmes différents: Rhodococcus fascians (un phytopathogène) et Pseudomonas aeruginosa (un pathogène opportuniste). Ainsi, deux métabolites ont été isolés en utilisant une combinaison de techniques chromatographiques couplées avec des tests qui évaluent l’expression de certains gènes impliqués dans les mécanismes de virulence de ces bactéries. Le premier est un nouvel isoflavanone prénylé, nommé perbergine, isolé à partir de l’extrait d’écorces de D. pervillei. Il a été montré que la perbergine cible l’expression du gène attR, codant un régulateur transcriptionnel de type LysR qui joue un rôle clé dans la régulation de l’expression des gènes de virulence de R. fascians et qui assure la transition entre un mode de vie épiphyte et le mode pathogène. En conséquence, nous avons également montré que l’expression de l’ensemble des gènes de virulence connu à ce jour chez R. fascians est également affectée alors que l’expression de gènes impliqués dans l’aptitude épiphyte de la bactérie n’est pas altérée. Par ailleurs, l’application de perbergine au moment de l’infection de plantes sensibles à R. fascians montre que cette molécule atténue la virulence de R. fascians in vivo, mettant en exergue le potentiel de la perbergine comme agent anti-infectieux. Le deuxième est un flavonoïde, connu sous le nom de catéchine, isolé de l’extrait d’écorces de C. albiflorum. La catéchine inhibe significativement l’expression des gènes régulateurs du mécanisme du quorum sensing chez P. aeruginosa tels que lasI, lasR, rhlI et rhlR et également lasB et rhlA dont l’expression dépend du quorum sensing. En conséquence, la production des facteurs de virulence tels que la pyocyanine et l’élastase est significativement affectée. Compte tenu de l’appauvrissement de notre arsenal d’antibiotiques et de leur inefficacité croissante, l’identification de ces composés ouvre une voie alternative de lutte contre les bactéries pathogènes et la multirésistance des bactéries pathogènes aux antibiotiques. Nos résultats démontrent également la richesse des plantes malgaches comme (res)sources de nouvelles molécules thérapeutiques et l’importance d’élargir le champ des cibles bactériennes à investiguer pour développer de nouvelles stratégies de lutte dans la guerre sans fin que nous menons contre les bactéries pathogènes.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished

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34

Mahmoud, Mohamed Attia Shaaban. "Bioactive Secondary Metabolites from Marine and Terrestrial Bacteria: Isoquinolinequinones, Bacterial Compounds with a Novel Pharmacophor". Doctoral thesis, 2004. http://hdl.handle.net/11858/00-1735-0000-0006-B0DD-7.

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35

Mahmoud, Mohamed Attia Shaaban [Verfasser]. "Bioactive secondary metabolites from marine and terrestrial bacteria: isoquinolinequinones, bacterial compounds with a novel pharmacophor / vorgelegt von Mohamed Attia Shaaban Mahmoud". 2005. http://d-nb.info/974034835/34.

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36

Gerard, Jeffery M. "Antibiotic secondary metabolities of bacteria isolated from the marine environment". Thesis, 1997. http://hdl.handle.net/2429/6676.

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Bioassay guided fractionation of the organic extracts obtained from cultures of several bacteria strains from the marine environment led to the isolation of twelve new and nine previously described secondary metabolites. The structures of these metabolites were determined by extensive chemical and spectroscopic analysis. Stable isotope incorporation experiments were also performed using one of the isolated strains to investigate the biosynthetic origins of the atoms in the principle active secondary metabolite. A culture of a Bacillus sp. isolated from the tissues of a marine worm collected near Loloata Island in Papua New Guinea produced a mixture of novel cyclic decapeptide antibiotics. Loloatins A (1), B (2), and C (3) were isolated and their structures were elucidated through NMR and mass spectrometric analysis. Peptides 1, 2, and 3 showed potent gram-positive antibiotic activity, including activity against drug resistant strains of Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus spp. Loloatin C (3) also showed strong Gram-negative antibiotic activity. Massetolides A - H (4 - 11), novel cyclic depsipeptides, as well as the known compound viscosin (12), were isolated from cultures of two Pseudomonas sp. isolated from a marine alga and a marine tube worm each collected near Masset Inlet, B.C. and Moira Island, B.C. respectively. Massetolide A (4) and viscosin (12) exhibited in vitro antimicrobial activity against Mycobacterium tuberculosis and Mycobacterium avium-intracellulare. The known compounds, AI77-B (13), AI77-F (14) as well as AI77-H (15), a new diastereomer of AI77-F(14), were isolated from several species of Bacillus pumilus isolated from various marine sources. AI77-B (13) exhibited cytotoxic and Gram-positive antibiotic activity. The absolute configuration of AI77-H (15) was determined by chemical modification and NMR analysis of the (R)- and (S)- a-methoxy-a-(trifluoromethyl)phenylacetate esters. Finally, stable isotope incorporation experiments were performed using a selected strain of Bacillus pumilus which demonstrated that AI77-B (13) is of mixed polyketide/amino acid biosynthetic origin.

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37

Yang, Yuan-Chien, e 楊婉鉛. "Secondary Metabolites from Two Soft Corals and A Marine-Derived Bacterium". Thesis, 2013. http://ndltd.ncl.edu.tw/handle/73883763192061455273.

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碩士
國立中山大學
海洋生物科技暨資源學系研究所
101
Continued studies on the secondary metabolites of the Formosan octocoral Isis hippuris collected at Orchid Island have led to the isolation of two new steroids 1–2, along with two known compounds 3–4. In addition, the coral species of the genus Sinularia (Alcyoniidae) are widespread in the different coral reefs all over the world, and were reported to contain a variety of secondary metabolites, comprising steroids, sesquiterpenoids, and diterpenoids. Chromatographic separation of organic extracts of S. numerosa resulted in the purification and structural elucidation of four new cembranoid derivatives 5–8, seven known compounds 913, 15 and 16, two new steroids 14 and 17, as well as one new α-tocopherol derivative 18. In continuing search for bioactive natural compounds from microorganisms, dimethyl pyridine-2,6-dicarboxylate 19 was isolated from marine bacterium Microbulbifer sp.. The structures of these metabolites were elucidated on the basis of extensive spectroscopic analysis (IR, UV, ESI-MS, specific optical rotation, 1D and 2D NMR) and by comparison of their spectral data with those of literature reports. Moreover, the absolute configuration of 6 was established by application of modified Mosher''s method. The cytotoxicity against A-549 (human lung epithelial carcinoma), HT-29 (human colon adenocarcinoma) and P-388 (mouse lymphocytic leukemia) cells activity of 1–2, 5–8, 13–14 and 17–19 as well as the anti-HCMV (human cytomegalovirus) activities of 5–6 and 17–18 were evaluated in vitro. Compounds 13 and 19 displayed cytotoxicity against P-388 cell line with ED50 values of 4.3 and 3.9 μg/mL, respectively.

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38

Rahman, Hafizur. "Unusual Sesquiterpenes: Gorgonenes and Further Bioactive Secondary Metabolites Derived from Marine and Terrestrial Bacteria". Doctoral thesis, 2008. http://hdl.handle.net/11858/00-1735-0000-0006-ACC0-2.

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39

Needham, Judy. "Secondary metabolites of bacteria obtained from the northeastern Pacific ocean : structure elucidation and biosynthetic studies". Thesis, 1993. http://hdl.handle.net/2429/6954.

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Investigation of the organic extracts obtained from cultures of four species of bacteria isolated from the northeastern Pacific ocean led to the isolation of eight new and six previously known secondary metabolites. The structures of the new compounds were elucidated by extensive spectroscopic analysis. In addition, the biogenetic origins of the atoms in two of the bacterial metabolites were probed using stable isotope incorporation experiments. A culture of the bacterium Serratia odorifera, isolated from a surface water sample taken near a Chinook salmon (Oncorhyncus tshawytscha) farm in Georgia Strait, British Columbia, produced the novel compound oncorhyncolide (34). Oncorhyncolide has a unique structure that is apparently not related to other known microbial metabolites isolated from terrestrial sources. Biosynthetic studies using stable isotopes have shown that all the carbons in oncorhyncolide are derived from acetate. The methyl branches in oncorhyncolide are derived from the C2 of acetate and are attached to carbon atoms derived from the carbonyl carbon, C1, of an acetate unit. This type of methyl branching is very rare in polyketide biosynthesis. Examination of the ethyl acetate extracts of a solid agar culture of Pseudomonas fluorescens obtained from an unidentified tunicate in Moira Sound, Alaska, led to the isolation of moiramides A (38), B (39) and C (40) as well as the known compound andrimid (41). The crude extract had shown antibacterial activity against Staphylococcus aureus and methicillinresistant S. aureus. Moiramide B and andrimid proved to be the compounds responsible for this activity. Biosynthetic studies on andrimid have shown that the acylsuccinimide ring is derived from valine, glycine and acetate. It has been proposed that the biosynthesis proceeds through a dipeptide-like intermediate formed from γ-amino-β-keto acids that are in turn formed from valine and glycine homologated with acetate, presumably via malonyl-CoA. Liquid cultures of Pseudomonas sp. 91V47 obtained from an abalone collected off Cortez Island in Georgia Strait, British Columbia, gave an extract that exhibited potent in vitro cytotoxicity. Bioassay-guided fractionation of the crude extract led to the isolation of three new δ-hydroxy acid rhizoxin analogs (44 to 46). The three new compounds showed significant in vitro activity against P388 murine leukemia. A marine isolate of the bacterium Bacillus pumilus, obtained from a sediment sample collected in Georgia Strait, British Columbia, produced an extract that exhibited antimicrobial activity against Staphylococcus aureus, methicillin-resistant S. aureus and S. saprophytics. The known compound AI-77-B (54), previously isolated from terrestrial and marine sources of B. pumilus, was found to be responsible for the antibacterial activity in the crude extract. A new AI-77-B analog, compound 57, was also isolated. Compound 57 showed antibacterial activity only at high concentrations. [chemical compound diagrams]

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40

Tabares, Paula. "Antimicrobial, anti-protease and immunomodulatory activities of secondary metabolites from Caribbean sponges and their associated bacteria". Doctoral thesis, 2011. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-67000.

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Marine sponges and their associated bacteria have been proven to be a rich source of novel secondary metabolites with therapeutic usefulness in infection and autoimmunity. This Ph.D. project aimed to isolate bioactive secondary metabolites from the marine sponges Amphimedon compressa, Aiolochroia crassa and Theonella swinhoei as well as from bacteria associated with different Caribbean sponges, specifically actinomycetes and sphingomonads. In this study, amphitoxin was isolated from the crude methanol extract of the sponge A. compressa and it was found to have antibacterial and anti-parasitic activities. Amphitoxin showed protease inhibitory activity when tested against the mammalian protease cathepsin B and the parasitic proteases rhodesain and falcipain-2. Furthermore, miraziridine A was identified in the dichloromethane extract of the sponge T. swinhoei collected offshore Israel in the Red Sea. Miraziridine A, a natural peptide isolated previously from the marine sponge Theonella aff. mirabilis, is a potent cathepsin B inhibitor with an IC50 value of 1.4 g/mL (2.1 M). Secondary metabolites from sponge-derived bacteria were also isolated and identified. A total of 79 strains belonging to 20 genera of the order Actinomycetales and seven strains belonging to two genera of the order Sphingomonadales were cultivated from 18 different Caribbean sponges and identified by 16S rRNA gene sequencing. Seven of these strains are likely to represent novel species. Crude extracts from selected strains were found to exhibit protease inhibition against cathepsins B and L, rhodesain, and falcipain-2 as well as immunomodulatory activities such as induction of cytokine release by human peripheral blood mononuclear cells. The isolates Sphingobium sp. CO105 and Lapillicoccus sp. BA53 were selected for cultivation, extraction and purification of bioactive metabolites based on initial bioactive screening results. The isoalloxazine isolumichrome was isolated from the strain Sphingobium sp. CO105 which inhibited the protease rhodesain with an IC50 of 0.2 M. The strain Lapillicoccus sp. BA53 was found to produce p-aminosalicylic acid methyl ester, which showed activity against the proteases cathepsins B and L, falcipain-2 and rhodesain. These results highlight the significance of marine sponge-associated bacteria to produce bioactive secondary metabolites with therapeutic potential in the treatment of infectious diseases and disorders of the immune system
Marine Schwämme und damit assoziierte Bakterien stellen eine wertvolle Quelle für neuartige Sekundärmetabolite mit therapeutischer Bedeutung für Infektion und Autoimmunität dar. Ziel dieser Doktorarbeit war die Isolierung bioaktiver Sekundärmetabolite aus den marinen Schwämmen Amphimedon compressa, Ailochroia crassa und Theonella swinhoei sowie von Bakterien, die mit verschiedenen karibischen Schwämmen assoziiert sind, wie z. B. Actinomyceten und Sphingomonaden. Amphotoxin wurde in dieser Studie aus dem methanolhaltigen Rohextrakt des Schwammes A. compressa isoliert. Es konnte sowohl eine antibakterielle als auch antiparasitäre Aktivität nachgewiesen werden. Der Einfluss von Amphotoxin auf die humane Protease Cathepsin B und die parasitären Proteasen Rhodesain und Falcipain-2 wurde ebenfalls getestet und es zeigte sich eine inhibitorische Wirkung gegenüber diesen Proteasen. Darüber hinaus wurde aus dem Dichlormethanextrakt des Schwammes T. swinhoei, der aus dem Roten Meer in Israel gewonnen wurde, Miraziridin A isoliert. Dieses natürliche Peptid war bereits aus dem marinen Schwamm Theonella aff. mirabilis isoliert worden. Miraziridin A ist ein starker Cathepsin B Inhibitor, der IC50 Wert beträgt 1.4 mg/mL (2.1 M). Sekundärmetabolite von aus Schwämmen gewonnenen Bakterien wurden ebenfalls isoliert und identifiziert. Es konnten 79 Stämme, die zu 20 verschiedenen Gattungen der Ordnung Actinomycetales, sowie sieben Stämme, die zu zwei Gattungen der Ordnung Sphingomonadales gehören, isoliert werden. Diese Bakterienstämme wurden aus ingesamt 18 verschiedenen karibischen Schwämmen kultiviert und mit Hilfe der 16S rRNA Sequenzierung bestimmt. Sieben dieser Stämme stellen wahrscheinlich neue Arten dar. Rohextrakte ausgewählter Stämme zeigten eine Proteasehemmung gegen die Cathepsine B und L, Rhodesain, Falcipain-2 sowie immunmodulatorische Wirkungen wie z.B. die Induktion der Cytokinfreisetzung durch menschliche periphere mononukleäre Blutzellen. Die Isolate Sphingobium sp. CO105 und Lapillicoccus sp. BA53 wurden für die Kultivierung, Extraktion und Aufreinigung von bioaktiven Metaboliten aufgrund der ersten vielversprechenden bioaktiven Testergebnisse ausgewählt. Das Isoalloxazin Isolumichrom wurde aus dem Stamm Sphingobium sp. CO105 isoliert, welches die Protease Rhodesain mit einem IC50-Wert von 0.2 M inhibiert. Für den Stamm Lapillicoccus sp. BA53 konnte nachgewiesen werden, dass er p-Aminosalicylsäuremethylester produziert, der eine Aktivität gegen die Proteasen Cathepsin B und L, Falcipain-2 und Rhodesain zeigt. Diese Ergebnisse unterstreichen die Bedeutung mariner, Schwamm-assoziierter Bakterien, die bioaktive sekundäre Metabolite mit therapeutischem Potential für die Behandlung von Infektionskrankheiten und Funktionsstörungen des Immunsystems produzieren

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41

Mahmoud, Hussien Ibrahim Al-Refa. "New and Bioactive Secondary Metabolites from Ma-rine and Terrestrial Bacteria: Ramthacin A, B, C, and Polyene Macrolides from Genetically Modified Bacteria". Doctoral thesis, 2008. http://hdl.handle.net/11858/00-1735-0000-0006-ACBA-1.

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42

Nair, Vimal. "Indole Alkaloids as Potential Leads in Drug Discovery and Further Secondary Metabolites from Terrestrial and Marine Bacteria". Doctoral thesis, 2010. http://hdl.handle.net/11858/00-1735-0000-0006-B084-F.

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43

Liang, Lanfang [Verfasser]. "Investigation of secondary metabolites of North Sea bacteria : fermentation, isolation, structure elucidation and bioactivity / vorgelegt von Lanfang Liang". 2003. http://d-nb.info/96850728X/34.

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44

Rahman, Md Hafizur [Verfasser]. "Unusual sesquiterpenes : gorgonenes and further bioactive secondary metabolites derived from marine and terrestrial bacteria / vorgelegt von Md. Hafizur Rahman". 2008. http://d-nb.info/996005021/34.

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45

Fotso, Serge [Verfasser]. "Higly cytotoxic kettapeptin, bhimamycins possessing unusual chromophores and further new secondary metabolites from terrestrial and marine bacteria / vorgelegt von Serge Fotso". 2006. http://d-nb.info/979079527/34.

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46

Refa'i, Mahmoud Hussien Ibrahim al [Verfasser]. "New and bioactive secondary metabolites from marine and terrestrial bacteria : ramthacin A, B, C, and polyene macrolides from genetically modified bacteria / vorgelegt von Mahmoud Hussien Ibrahim Al-Refa'i". 2008. http://d-nb.info/994029926/34.

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47

Mahmoud, Khaled Attia Shaaban. "Nafisamycin, Cyclisation Product of a New Enediyne Precursor, Highly Cytotoxic Mansouramycins, Karamomycins Possessing a Novel Heterocyclic Skeleton and Further Unusual Secondary Metabolites from Terrestrial and Marine Bacteria". Doctoral thesis, 2009. http://hdl.handle.net/11858/00-1735-0000-0006-ACC1-F.

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48

Mahmoud, Khaled Attia Shaaban [Verfasser]. "Nafisamycin, cyclisation product of a new enediyne precursor, highly cytotoxic mansouramycins, karamomycins possessing a novel heterocyclic skeleton and further unusual secondary metabolites from terrestrial and marine bacteria / vorgelegt von Khaled Attia Shaaban Mahmoud". 2008. http://d-nb.info/1003281990/34.

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49

Martens, Torben [Verfasser]. "Untersuchungen auf Sekundärstoffproduktion und physiologische Charakterisierung von marinen heterotrophen Bakterien aus dem deutschen Wattenmeer = Secondary metabolite production and physiological characterisation of marine heterotrophic bacteria from the German Wadden Sea / von Torben Martens". 2005. http://d-nb.info/977583546/34.

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50

Elazreg, Karima. "Endophytes of commercial Cranberry cultivars that control fungal pathogens". Thesis, 2020. http://hdl.handle.net/1866/24726.

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Les endophytes sont des microorganismes (généralement des bactéries et des champignons) qui vivent dans les tissus végétaux mais n'activent pas le système immunitaire/défense des plantes, contrairement aux pathogènes végétaux qui activent généralement les réponses immunitaires des plantes. Des recherches récentes ont montré que pratiquement toutes les plantes cultivées en plein champ contiennent un certain nombre d'endophytes, et que certains endophytes stimulent la croissance des plantes et renforcent la résistance contre les agents pathogènes. Les endophytes sécrètent des composés chimiques (métabolites secondaires) qui suppriment la croissance des agents pathogènes, un processus connu sous le nom de biocontrôle. En raison de ces propriétés de biocontrôle, les endophytes sont une alternative potentielle aux pesticides chimiques pour lutter contre les maladies des plantes. En conséquence, le biocontrôle est devenu un domaine de recherche important. Mon projet de recherche comportait les objectifs spécifiques suivants : (i) isoler les endophytes des plants de canneberges acquis auprès de deux producteurs commerciaux de canneberges de la variété Stevens situés au Québec, Canada (Bieler Cranberries Inc, et Gillivert Inc.) ; (ii) tester l'activité de biocontrôle des endophytes contre une collection de champignons pathogènes et ensuite inoculer les endophytes les plus actifs dans des plants de canneberges obtenus par germination de la variété Stevens (Bieler Cranberries Inc. ) et Scarlet Knight (Daniele Landreville) ; et (iii) identifier des groupes de gènes de métabolites secondaires en séquençant, assemblant et annotant le génome d'un endophyte qui présentait de fortes caractéristiques de biocontrôle. Dans le cadre de ce projet de recherche, des tests antagonistes in vitro ont été réalisés avec des endophytes de la canneberge et un champignon pathogène, qui ont montré que Pseudomonas sp. CSWB3, Pseudomonas sp. CLWB12 et la souche fongique Lachnum sp. EFK28 étaient les plus actifs et ces souches ont donc été sélectionnées pour des études plus approfondies. Des expériences de germination de semis in vitro et d'inoculation d'endophytes ont montré que les souches bactériennes Pseudomonas sp. CSWB3 et Pseudomonas sp. CLWB12 amélioraient la croissance des semis de canneberges de la variété Stevens. Comme les Pseudomonas sp. CSWB3 et Pseudomonas sp. CLWB12 ont tous deux un effet antagoniste élevé sur les champignons pathogènes, un seul (Pseudomonas sp. CSWB3) a été soumis à une analyse du génome. Le séquençage, l'assemblage, l'annotation et l'analyse du génome de Pseudomonas sp. CSWB3 a révélé que cette souche possède cinq groupes de gènes biosynthétiques de métabolites secondaires qui codent pour les protéines responsables de la biosynthèse des composés antifongiques/antimicrobiens : pyrrolnitrine, pyoluteorine, putisolvine, 2,4-diacétylephloroglucinol, bicornutine A1 et bicornutine A2. Sur la base des résultats de ces travaux, nous concluons que certains endophytes de la canneberge qui possèdent des groupes de gènes codant pour des métabolites secondaires antifongiques peuvent supprimer les pathogènes fongiques et améliorer la croissance des plantes.
Endophytes are microorganisms (typically bacteria and fungi) that live within plant tissue but do not activate the plant defense/immune system, unlike plant pathogens that typically do activate plant immune responses. Recent research has shown that virtually all plants grown under field conditions contain a number of endophytes, and that certain endophytes stimulate plant growth and enhance resistance against pathogens. Endophytes secrete chemical compounds (secondary metabolites) that suppress pathogen growth, a process known as biocontrol. Because of these biocontrol properties, endophytes are a potential alternative to chemical pesticides for combatting plant disease. Accordingly, biocontrol has become an important field of research. My research project was comprised of the following specific aims: (i) isolate endophytes from cranberry plants that were acquired from two commercial producers of cranberries of the Stevens variety located in Quebec, Canada (Bieler Cranberries Inc, and Gillivert Inc.); (ii) test the biocontrol activity of endophytes against a collection of fungal pathogens and then inoculate the most active endophytes into cranberry seedlings that were obtained by germinating Stevens (Bieler Cranberries Inc.) and Scarlet Knight (Daniele Landreville) seeds; and (iii) identify secondary metabolite gene clusters by sequencing, assembling, and annotating the genome of one endophyte that exhibited strong biocontrol characteristics. As part of this research project, in vitro antagonistic tests were conducted with cranberry endophytes and fungal pathogen, which showed that Pseudomonas sp. CSWB3, Pseudomonas sp. CLWB12, and the fungal strain Lachnum sp. EFK28 were the most active and therefore these strains were selected for further studies. In vitro seedling germination and endophyte inoculation experiments showed that the bacterial strains Pseudomonas sp. CSWB3 and Pseudomonas sp. CLWB12 enhanced the growth of cranberry seedlings of the Stevens variety. Since Pseudomonas sp. CSWB3 and Pseudomonas sp. CLWB12 both had a high antagonistic effect on fungal pathogens, only one (Pseudomonas sp. CSWB3) was subjected to genome analysis. Sequencing, assembly, annotation, and analysis of the Pseudomonas sp. CSWB3 genome revealed that this strain possesses five secondary metabolite biosynthetic gene clusters that encode proteins responsible for the biosynthesis of the antifungal/antimicrobial compounds pyrrolnitrin, pyoluteorin, putisolvin, 2,4-diacetylephloroglucinol, bicornutin A1, and bicornutin A2. Based on the results of this work, we conclude that certain cranberry endophytes that possess gene clusters encoding antifungal secondary metabolites can suppress fungal pathogens and enhance plant growth.

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