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Sadikalay, Syndia. "Influence des rejets humains et animaux sur la diffusion de l'antibiorésistance à l'homme, aux animaux et à l'environnement en Guadeloupe". Electronic Thesis or Diss., Antilles, 2018. http://www.theses.fr/2018ANTI0251.
Pełny tekst źródłaThe pressure of selection related to the overuse of antibiotics in human and veterinary medicines is responsible for this increase, but the environment also plays a role in the diffusion of these resistances.In Guadeloupe, very few things are known on the state of resistance to antibiotics, but both veterinary and human uses are intense and amendments resulting from human and animal wastes are widely used.In Guadeloupe, the use of waste from animal, plant and human activities in crop production does not appear to favor E. coli resistant strains spreading from the environment to humans. However, composting quality, soil physicochemical characteristics and climatic conditions should be taken into account when planning amendments to reduce the exposure risk, spread and persistence of E. coli resistant strains.Fifteen strains of E. coli were isolated from horses feces were isolated during their antibiotic treatment, three in the first horse and 12 in the second. Profiles of antibiotic resistance were congruent with the plasmid analysis, genotypes for resistance genes detected using WGS, and with the phylogenetic analysis based on the core genome. Three clones and four singletons could be distinguished indicating that a high genetic diversity exists among E. coli producing ESBL. This study evidenced the persistence of E. coli producing ESBL in the microbiota of horses treated with antibiotics. This study was able to demonstrate the resurgence of resistant phenotypes even before the first day of treatment with persistence of these strains more than one month after treatment. The absence of detection of E. coli producing ESBL was evedenced a few months after treatment. Thus, the diversity of antibiotic-resistant pathogenic microorganisms has probably higher than that described in previous studies
Gbaguidi, Bénédicte. "Caractérisation structurale de LmrP, protéine membranaire associée à la résistance bactérienne aux antibiotiques, dans son environnement lipidique". Doctoral thesis, Universite Libre de Bruxelles, 2007. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210714.
Pełny tekst źródłaNgaiganam, Edgarthe. "Etude de la résistance aux antibiotiques chez les animaux et dans l'environnement en France". Thesis, Aix-Marseille, 2019. http://www.theses.fr/2019AIXM0241.
Pełny tekst źródłaEmergence and spread of multidrug-resistant bacteria (MDR) are a major public health problem worldwide. Nowadays, some antibiotics are increasingly used in veterinary medicine as well as in human medicine and also in agriculture, particularly in animal feed and aquaculture. Therefore, resistance to β-lactams, carbapenems and colistin is not only observed in pathogenic bacteria, but also in environmental organisms that serve as reservoirs and vectors for the spread of resistance. There are still unknown reservoirs of multi-resistant bacteria and antibiotic resistance genes. Thus, the understanding of reservoirs and the transmission of antibiotic resistance genes are essential to control their emergence and their spread in the community. In France, the use of antibiotics as a growth factor or prophylaxis is limited in the production of animals for consumption. It is in this respect that our thesis project is aimed at: (i) Isolation and characterization of extended-spectrum β-lactamase producing bacteria (ESBL) and carbapenemase-producing bacteria from environmental samples in Marseille; (ii) Investigation of colistin resistance in Gram-negative bacteria isolated from water samples and animals. A review of the literature on the role of birds as reservoirs of multidrug-resistant bacteria was conducted as an introduction to this thesis project. Our results thus showed the possibility of horizontal transfer of antibiotic resistance genes from animals and the environment to humans and suggest a potential zoonotic transmission between humans and animals. It would be important to monitor antibiotic resistance in non-hospital settings and primarily in the environment
Guyomard, Rabenirina Stephanie. "Résistance aux antibiotiques des entérobactéries en Guadeloupe : importance en mileu communautaire et diffusion environnementale". Thesis, Antilles, 2016. http://www.theses.fr/2016ANTI0074/document.
Pełny tekst źródłaAntibiotic resistance has become a major public health concern worldwide that could lead to therapeutic impasse. The overuse and misuse of antibiotics in human medicine but also in veterinary medicine is largely responsible for the proliferation and spread of multi-drug resistant (MDR) bacteria. Enterobacteriaceae are subject to this selective pressure, as the digestive tract is their main reservoir. Moreover, thanks to their ability to exchange genetic material, they can acquire new antibiotic resistance determinants. Through human and animal waste, antimicrobial resistant bacteria can spread in the environment. However, the environment is also a supplier for antibiotic resistance since environmental bacteria naturally harbor antibiotic resistance determinants.In Guadeloupe, except for data from MDR bacteria surveillance in the hospital, no studies concerning antibiotic resistance had been carried out. The objectives of this thesis were (i) to evaluate the antimicrobial resistance in the community by studying antimicrobial susceptibility of Enterobacteriaceae strains isolated from community-acquired urinary tract infection and (ii) to study the environmental spread of antimicrobial resistant Enterobacteriaceae (AREs) in river and sea waters receiving effluents from wastewater treatment plants but also in terrestrial wildlife.Our work highlighted the environmental spread of AREs linked to human activities. WWTPs discharge has been identified as a source of AREs, especially ESBLEs, in the environment. Nevertheless, other human activities may release ARB in the environment, and some will be explored in further studies. Thus, prevention requires an overall improvement in waste management, and wastewater discharge should occur in open sea as often as possible
Almakki, Ayad Qasim Mahdi. "Résistance aux antibiotiques dans des eaux urbaines péri-hospitalières considérées dans un continuum hydrologique". Electronic Thesis or Diss., Montpellier, 2017. http://www.theses.fr/2017MONTS002.
Pełny tekst źródłaAquatic ecosystems subjected to anthropic pressures are places of rapid evolution of microbial communities. They are likely hotspots for emergence of infectious disease agents resistant to antibiotics. The city of Montpellier is located in a small watershed that undergoes brutal rainfall episodes and strong demographic pressures. A hospital is located in a runoff area including two small urban rivers originating from karstic groundwater few kilometers upstream. The aim of the study is to explore bacterial communities in urban rivers flowing near hospital settings in order to evaluate the influence of runoffs on antibiotics resistance in the bacterial communities. Bacterial communities are also described in upstream karstic aquifers.An introductive section presents the methods available for studying antimicrobial resistance in environment and then reviews comprehensively bibliography on antibiotics resistance in urban runoffs. This part supports the experimental strategies. The method developed herein, called community Inhibitory Concentration (c-IC) determination is combined to taxonomic richness description to provide a tool that gives a rapid snapshot of resistant bacterial communities in aquatic environments. A strategy derived from c-IC approach allows the exploration of bacterial resistance in the urban hydrologic system near the hospital and in karstic aquifers. The collected microbiological data has been completed by hydrological, hydrogeological, climatic and physico-chemical data.The impact of very low concentration of antibiotics on the bacterial community structure in various water bodies was demonstrated and appeared as an indicator of the vulnerability of ecosystems to antimicrobial pressures. The taxonomic repertory of the urban river communities was described and its dynamics was compared to environmental conditions. Hospital vicinity significantly increase the prevalence of resistant bacteria compared to a similar urban area remote from hospital. Diverse clinically relevant cephalosporins and carbapenems resistant bacteria have been isolated. Surprisingly, a NDM-producing Escherichia coli, which is a highly resistant and emerging pathogen was reported for the first time in a French River. The clone was detected in two independent sampling showing its persistence. The blaNDM-5 gene and its surrounding sequences were described on a transferable IncX3 plasmid, indicating possible genetic transfer to other bacteria. The antimicrobial resistance in karst groundwater varied in time and space and was hardly compared with that described in related rivers.In urban settings, water quality and infectious risk is generally assessed on sewers and wastewater treatment plants effluents. This study shows that runoff waters in urbanized area contribute to the emergence and dissemination of antimicrobial resistance. Considering the worrisome epidemiology of infectious diseases, it urges to decipher all environmental reservoirs for resistant bacteria in order to complete knowledges about the epidemiological cycle of antimicrobial resistance and try to break or slow down it
Touzri-Tekari, Souad. "Difficultés de mobilisation de raisonnements écosystémiques chez des élèves et des futurs enseignants dans des problèmes d'environnement et de santé : le cas de l'adaptation des micro-organismes à l'usage des antibiotiques". Nantes, 2006. http://www.theses.fr/2006NANT3001.
Pełny tekst źródłaAlmakki, Ayad Qasim Mahdi. "Résistance aux antibiotiques dans des eaux urbaines péri-hospitalières considérées dans un continuum hydrologique". Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTS002/document.
Pełny tekst źródłaAquatic ecosystems subjected to anthropic pressures are places of rapid evolution of microbial communities. They are likely hotspots for emergence of infectious disease agents resistant to antibiotics. The city of Montpellier is located in a small watershed that undergoes brutal rainfall episodes and strong demographic pressures. A hospital is located in a runoff area including two small urban rivers originating from karstic groundwater few kilometers upstream. The aim of the study is to explore bacterial communities in urban rivers flowing near hospital settings in order to evaluate the influence of runoffs on antibiotics resistance in the bacterial communities. Bacterial communities are also described in upstream karstic aquifers.An introductive section presents the methods available for studying antimicrobial resistance in environment and then reviews comprehensively bibliography on antibiotics resistance in urban runoffs. This part supports the experimental strategies. The method developed herein, called community Inhibitory Concentration (c-IC) determination is combined to taxonomic richness description to provide a tool that gives a rapid snapshot of resistant bacterial communities in aquatic environments. A strategy derived from c-IC approach allows the exploration of bacterial resistance in the urban hydrologic system near the hospital and in karstic aquifers. The collected microbiological data has been completed by hydrological, hydrogeological, climatic and physico-chemical data.The impact of very low concentration of antibiotics on the bacterial community structure in various water bodies was demonstrated and appeared as an indicator of the vulnerability of ecosystems to antimicrobial pressures. The taxonomic repertory of the urban river communities was described and its dynamics was compared to environmental conditions. Hospital vicinity significantly increase the prevalence of resistant bacteria compared to a similar urban area remote from hospital. Diverse clinically relevant cephalosporins and carbapenems resistant bacteria have been isolated. Surprisingly, a NDM-producing Escherichia coli, which is a highly resistant and emerging pathogen was reported for the first time in a French River. The clone was detected in two independent sampling showing its persistence. The blaNDM-5 gene and its surrounding sequences were described on a transferable IncX3 plasmid, indicating possible genetic transfer to other bacteria. The antimicrobial resistance in karst groundwater varied in time and space and was hardly compared with that described in related rivers.In urban settings, water quality and infectious risk is generally assessed on sewers and wastewater treatment plants effluents. This study shows that runoff waters in urbanized area contribute to the emergence and dissemination of antimicrobial resistance. Considering the worrisome epidemiology of infectious diseases, it urges to decipher all environmental reservoirs for resistant bacteria in order to complete knowledges about the epidemiological cycle of antimicrobial resistance and try to break or slow down it
Deredjian, Amélie. "Les métaux lourds dans les écosystèmes anthropisés : une pression favorisant la sélection de pathogènes opportunistes résistants à des antibiotiques ?" Phd thesis, Université Claude Bernard - Lyon I, 2010. http://tel.archives-ouvertes.fr/tel-00834182.
Pełny tekst źródłaSadikalay, Syndia. "Influence des rejets humains et animaux sur la diffusion de l'antibiorésistance à l'homme, aux animaux et à l'environnement en Guadeloupe". Thesis, Antilles, 2018. http://www.theses.fr/2018ANTI0251/document.
Pełny tekst źródłaThe pressure of selection related to the overuse of antibiotics in human and veterinary medicines is responsible for this increase, but the environment also plays a role in the diffusion of these resistances.In Guadeloupe, very few things are known on the state of resistance to antibiotics, but both veterinary and human uses are intense and amendments resulting from human and animal wastes are widely used.In Guadeloupe, the use of waste from animal, plant and human activities in crop production does not appear to favor E. coli resistant strains spreading from the environment to humans. However, composting quality, soil physicochemical characteristics and climatic conditions should be taken into account when planning amendments to reduce the exposure risk, spread and persistence of E. coli resistant strains.Fifteen strains of E. coli were isolated from horses feces were isolated during their antibiotic treatment, three in the first horse and 12 in the second. Profiles of antibiotic resistance were congruent with the plasmid analysis, genotypes for resistance genes detected using WGS, and with the phylogenetic analysis based on the core genome. Three clones and four singletons could be distinguished indicating that a high genetic diversity exists among E. coli producing ESBL. This study evidenced the persistence of E. coli producing ESBL in the microbiota of horses treated with antibiotics. This study was able to demonstrate the resurgence of resistant phenotypes even before the first day of treatment with persistence of these strains more than one month after treatment. The absence of detection of E. coli producing ESBL was evedenced a few months after treatment. Thus, the diversity of antibiotic-resistant pathogenic microorganisms has probably higher than that described in previous studies
Oberle, Kenny. "Devenir des antibiotiques et des populations d'Escherichia coli et d'Enterococcus spp. dans les hydrosytèmes de surface". Phd thesis, Université de Rouen, 2012. http://tel.archives-ouvertes.fr/tel-00828033.
Pełny tekst źródłaStalder, Thibault. "Implication des effluents d'activités hospitalières et de la filière carnée sur la dissémination de l’antibiorésistance : Dynamique des intégrons de l’émission au rejet". Limoges, 2012. https://aurore.unilim.fr/theses/nxfile/default/38891773-0b9d-4f34-a342-a2da4509ecac/blobholder:0/2012LIMO4031.pdf.
Pełny tekst źródłaThis work aims to assess the global contribution and influence of hospital activities and livestock industries on the dissemination of antibiotic resistance in the environment. For this purpose, the dynamics of a genetic element used as a biomarker of antibiotic resistance, the resistance integrons (RI), was monitored. Indeed, a wide range of solids and liquids biological wastes from different geographical and anthropogenic origins are involved in the antibiotic resistance dissemination. However, we showed that hospital effluents contained a high proportion of RIs in bacterial communities, and the gene cassette (GC) content of class 1 RI mainly showed antibiotic resistance GCs. Hospital effluent contributed to 14% of the Ris introduced in the waste water treatment plant (WWTP). While urban effluents diluted the risk associated with hospital effluent, RIs harboring GCs of clinical interest, such as ESBLencoding GCs, were found in these effluents unaffected by medical and industrial activities. The WWTP did not reduce the proportion of RIs in treated effluents but eliminated a fraction of the bulk of GCs from the influent. Large quantities of RIs harboring antibiotic-resistance GCs, and also GCs with unknown functions were released daily into the environment. In addition, a pilot study showed that the treatment of hospital wastewater by the activated sludge process promoted the increase of IR and potentially pathogenic bacteria in the sewage sludge, and consequently increased the issue of antibiotic- resistance spread in these matrices. Finally the use of RI as biomarker to assess the efficiency of advanced treatment processes for hospital effluents (membrane bioreactor ozonation, activated carbon) highlighted the effectiveness of membrane bioreactors using ultrafiltration to reduce both bacteria and IR of anthropogenic origins
Youenou, Benjamin. "Les sols anthropisés, incubateurs d'agents bactériens pathogènes de l'homme : typage génétique, métabolique et antibio-résistance d'agents opportunistes". Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10150.
Pełny tekst źródłaOpportunistic bacterial pathogens (obp) of Man are found in hospital setting where they are responsible for nosocomial infections as well as in terrestrial and aquatic natural environments. Obp often show high intrinsic antibiotic resistance level. Moreover, the intensive use of antibiotics in clinical settings can lead to the emergence of "Multi Drug Resistant" strains. The anthropisation of the natural environment leads to modifications in bacterial diversity of these environments and can affect the prevalence and the antibiotic resistance properties of obp. My research focused on the impact of organic amendments on the prevalence, genetic diversity and antibiotic resistance properties of obp. A study on the species Stenotrophomonas maltophilia, Pseudomonas aeruginosa and the “Burkholderia cepacia complex" (Bcc) was conducted on sites in Burkina Faso amended or not with raw urban wastes. This study showed differences in antibiotic resistance properties between the 3 models. S. maltophila frequently showed MDR phenotypes unlike P. aeruginosa and Bcc. A comparative genomics study between S. maltophilia strains from environmental or clinical origin showing sensitive or MDR phenotypes was performed to elucidate the genetic origins of heterogeneity in the resistance phenotypes. A variation in the efflux pumps content was observed between strains. The expression of an efflux pump specific to an environmental MDR strain was then evaluated and confirmed its likely involvement in antibiotic resistance and adaptation to environmental parameters such as temperature
Legrand, Baptiste. "Analyse d'interactions moléculaires par RMN : Étude de la DHFR en présence d'osmolytes et structures de pseudopeptides antimicrobiens en environnement". Phd thesis, Rennes 1, 2009. https://tel.archives-ouvertes.fr/tel-00453405.
Pełny tekst źródłaThe osmolytes are small molecules accumulated by cells of a wide variety of organisms in response to hyperosmotic stress to maintain the cellular volume. Nervetheless, enzyme activity is inhibited by these cosolutes and the molecular basis of their effects on the proteins properties is of great interest. We studied the DHFR in presence of the osmolytes. We demonstrate that its overall structure is maintained. While the osmolytes stabilize the DHFR structure, they inhibit its activity at the same time. The k[index :]off, of substrate analogues decreases with increasing the osmolyte concentrations and reflects the variation of DHFR catalytic rate. The study of the DHFR dynamic on several timescales gives answer of the origins of the DHFR inhibition in presence of osmolytes. The second chapter concerns the study of the structure-activity relationship of antimicrobial peptides. The main objective of this project is to develop new drugs. We solved NMR solution structure of in various model membranes
Gay, Noellie. "Homme, animal, environnement : quel est le principal réservoir d’Entérobactéries productrices de bêta-lactamases à spectre étendu dans le Sud-Ouest de l’océan Indien ?" Thesis, La Réunion, 2019. http://www.theses.fr/2019LARE0024.
Pełny tekst źródłaBacterial antibiotic drug resistance is a worldwide health issue affecting human, animal, and agriculture. Extended-spectrum bêta-lactamase-producing Enterobacteriaceae (ESBL-E), mutidrug-resistant bacteria, are a main health priority for the South-western Indian Ocean (SWIO) composed of islands (i.e. Madagascar, Maurice, Mayotte, Les Seychelles, l’Union des Comores et La Réunion). The main objective of this PhD thesis was estimating the ESBL-E prevalence in the three « One Heath approach » compartments (human, animal, environment) in order to identify the main ESBL-E reservoir in IO. This prevalence was independently estimated for each compartment by a sectorial approach and by a holistic approach connecting all compartments spatially and temporally.Both approaches suggest that livestock could be the main ESBL-E reservoir in IO and point out permeability between these three compartments in Madagascar. If the idea of a main reservoir of ESBL-E in livestock seems plausible, its contribution to human colonisation could differ between SWIO territories. Indeed, human direct and/or undirect exposure to this reservoir could be reduced in high-income countries (i.e. Seychelles, La Réunion) but significant for low-income countries (i.e. Madagascar, Union des Comores). In the absence, or reduced application, of food safety, sanitation, and drinking water access, the exposure to ESBL-E from livestock could be substantial in SWIO low-income countries. Consequently, the relative contribution of livestock in human ESBL-E subsequent colonisation could be significant in low-income countries but currently understudied. Research on that topic should strengthen antibiotic drug resistance control measures in low sanitation contexts
Laval, Lucie. "Les intégrons comme marqueurs de pollution anthropique dans l'environnement". Electronic Thesis or Diss., Limoges, 2022. http://www.theses.fr/2022LIMO0083.
Pełny tekst źródłaAntimicrobial resistance (AMR) is a major public health issue. It is now necessary to tackle AMR globally, in humans, animals and in the environment (« One Health » approach). Among genetic elements involved in AMR, integrons play a key role. Integrons are bacterial genetic elements able to capture and express antibiotic resistance genes in the form of gene cassettes and are distinguished according to several classes. In the environment, class 1 integrons are considered as a good marker of anthropogenic pollution and are used to study AMR dissemination; however, little is known about their genes cassettes content (or « cassettome »). In the first part of this thesis, we studied the « cassettomes » of integrons in the effluents of healthcare facilities of the Nouvelle-Aquitaine Region and showed that they were stable over times and similar to each other despite large differences in healthcare activities between the facilities. The « cassettomes » were mainly composed of aminoglycosides and β-lactams resistance gene cassettes, the last one being the main antibiotics delivered in hospitals. We also characterized the « cassettomes » of slaughterhouse effluents and showed that the « cassettomes » of class 1 integrons were different from those of healthcare facilities effluents. The second part of this thesis work showed different prevalences of integrons in Aeromonas strains infecting/colonizing fish subjected to different antibiotic selective pressures. We showed that integrons were more prevalent in fish populations subjected to stronger antibiotic selective pressure contrary to Aeromonas from wild fish where they were not detected. Our work shows that integrons and more specifically « cassettomes » are good markers in the environment to differentiate different types of effluents (healthcare facilities versus slaughterhouses) and secondly to reflect an antibiotic selective pressure exerted on fish
Nguyen, Trong Hiep. "Hypermutabilité et résistance aux antibiotiques chez Staphylococcus aureus". Caen, 2006. http://www.theses.fr/2006CAEN2018.
Pełny tekst źródłaIn cystic fibrosis, hypermutable variants of Staphylococcus aureus are frequently isolated. We have characterized new mutations of ribosomal protein L4 responsible for macrolide resistance. Telithromycin related to macrolides displays a low ability to select for resistant mutants in pneumococci. We have carried out a study of selection in 6 hypermutable and non hypermutable clinical and laboratory isolates of S. Aureus in the presence of erythromycin or telithromycin. Telithromycin was weakly less selective than erythromycin. Mutations of ribosomal proteins L22 and L4 are most often detected in strains selected by telithromycin and erythromycin, respectively. Mutants are selected more rapidly in hypermutable strains. Then, we have studied the fluoroquinolones because of the usual mechanism of resistance to these antibiotics by mutation. Resistance to fluoroquinolones appeared significantly more frequent in clinical hypermutable isolates of S. Aureus (non cystic fibrosis) than in non hypermutable isolates. One of the hypermutable isolate had a deletion of the mutator operon mutSL. Hypermutable isolates combined several mutations in the target of quinolones. Since several hypermutable S. Aureus did not have mutSL mutations, we have searched for homologues of mutator genes of E. Coli and Bacillus subtilis in S. Aureus MW2. Six candidate genes (miaA, nth, ung, recA, recG, et mutS2) have been selected. After inactivation by insertion of a thermosensitive plasmid and complementation by the wild-type gene, only the nth gene has shown a role in hypermutability in S. Aureus
Mammeri, Hedi. "Mécanismes émergents de résistance aux antibiotiques : céphalosporinases à spectre étendu et résistance plasmidique aux quinolones". Paris 5, 2006. http://www.theses.fr/2006PA05D035.
Pełny tekst źródłaß-Lactams and fluoroquinolones constitute the most prescribed antibiotics used in therapeutics. Recently, two novel acquired mechanisms of resistance were described : the plasmid-borne qnrA gene, encoding a pentapeptide that prevents binding of fluoroquinolones on their targets, and the extended-spectrum AmpC ß-lactamases, which display an increased hydrolysis activity toward oxyiminocephalosporins. During this work, we have characterized several novel extended-spectrum cephalosporinases, mainly produced by Escherichia coli isolates, identified new structural modifications responsable for the extension of the hydrolysis spectrum and revealed the genetic diversity of the ampC genes in E. Coli. We have also described the emergence of the qnrA gene in Europe, the involvement of its genetic environment in its expression, the absence of effect of QnrA on the bactericidal activity of fluoroquinolones, and the origin of qnrA naturally present on the chromosome of Shewanella algae
Bador, Julien. "Résistance aux antibiotiques par mécanisme d'efflux chez Achromobacter xylosoxidans". Phd thesis, Université de Bourgogne, 2013. http://tel.archives-ouvertes.fr/tel-00990010.
Pełny tekst źródłaHocquet, Didier. "Résistance aux antibiotiques par efflux actif chez Pseudomonas aeruginosa". Besançon, 2003. http://www.theses.fr/2003BESAA003.
Pełny tekst źródłaCharpentier, Emmanuelle. "Étude de la résistance aux antibiotiques chez Listeria spp". Paris 6, 1995. http://www.theses.fr/1995PA066562.
Pełny tekst źródłaAmoureux-Boyer, Lucie. "Achromobacter xylosoxidans : épidémiologie au centre de ressources et de compétences de la mucoviscidose de Dijon et réservoir environnemental". Thesis, Dijon, 2013. http://www.theses.fr/2013DIJOS070/document.
Pełny tekst źródłaAchromobacter xylosoxidans is an aerobic nonfermentative Gram-Negative rod considered as an important emerging pathogen among cystic fibrosis (CF) patients worldwide. In Dijon (Burgundy), the prevalence of colonised patients is high among CF patients and increasing among non-CF hospitalised patients. The natural habitat of this organism as well as the possible sources of patient contamination remain unknown.The aims of this study were to report the first epidemiological data about A. xylosoxidans in a French CF centre and to identify potential reservoirs of this organism in Burgundy. In a retrospective study, all the isolates recovered from the patients affiliated with our centre in 2010 since their first visit were analysed. Out of 120 patients, 21 (17.5%) had at least one positive culture with A. xylosoxidans. Genotyping analysis by Pulsed Field Gel Electrophoresis revealed that cross-Contamination was very rare. Acquired resistance was frequent to ciprofloxacin (since primocolonisation), to ceftazidime and to carbapenems (in persistent colonisations). Thanks to our protocol designed to detect A. xylosoxidans in environment, a total of 50 strains were isolated in hospital (33 isolates), domestic (9 isolates) and outdoor (8 isolates) samples, mainly in handwashing sinks, showers, and water. These environmental isolates shared characteristics with clinical ones: 6 genotypes in common and a constant resistance to ciprofloxacin. These results reveal potential sources of contamination for the patients at home or in hospital. Further studies are needed to help understanding the emergence of this bacterium and the mechanisms involved in acquired antibiotic resistance
Boumghar-Bourtchai, Leyla. "Mécanismes émergents de résistance bactérienne aux inhibiteurs de synthèse protéique". Caen, 2008. http://www.theses.fr/2008CAEN3011.
Pełny tekst źródłaMhaya, Amel. "Analyse de la résistance aux antibiotiques chez les entérobactéries et étude d’une potentielle voie alternative aux traitements antibiotiques". Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0420.
Pełny tekst źródłaThe increase of multidrug-resistant bacteria (BMR) to antibiotics is a major public health problem. The first objective of the thesis was to search for the presence of BMR, poorly documented in the community in Tunisia. For the first time, we isolate a Klebsiella pneumoniae belonging to the sequence type ST147 producing carbapenemase NDM-1 in this setting, at Sfax. Our data also indicate an unusually high proportion (47%) of Escherichia coli producing committally two extended-spectrum ß-lactamases. Four of them, with CTX-M-15 and CTX-M-27, are divided into 2 clonal strains of type A-ST617 (2 isolates) and B2-ST131 subclade C2 (2 isolates). All contain a plasmid with the same allelic combination, F31: A4: B1; suggesting a possible dissemination of this replicon. In another study (community-based, Djerba), a multiresistant clonal strain Eh22 of Enterobacter hormaechei, containing a 300 kbp conjugative plasmid of IncHI2, was isolated from 2 patients without apparent epidemiological relationship. The plasmid was sequenced and shows the presence of different resistance genes including 4 genes encoding β-lactamases (blaTEM-1, blaDHA-1, blaCTX-M-3 and blaSHV-12). In a second part, we studied in Eh22, the resistance to colistin (CS), antibiotic of last resort. After selection of an in vitro mutant, we showed for the first time, in Enterobacter spp, that this resistance can be due to a mutation in the gene encoding MgrB, a negative regulator of the 2-component PhoQP system that allows the synthesis of cationic residues on lipopolysaccharide, target of CS. In the last part, bacteriocins-like molecules active on BMR were searched in a collection of Bacillus thurengiensis. One of them, BUPM103, inhibits the growth of BMR. The gene for a potential bacthuricin F103 (11 kDa) was identified by an in silico analysis and it was produced in E. coli. The filtered supernatant secretion showed a growth inhibitory activity against a multiresistant K. pneumoniae, in contrast to control (without secretion). This recombinant bacthuricine could constitute a therapeutic alternative for the BMR treatment
Brega, Sara. "Mécanismes de résistance de Plasmodium vivax aux antipaludiques". Lyon 1, 2005. http://www.theses.fr/2005LYO10181.
Pełny tekst źródłaTremblay, Simon. "Étude moléculaire du recrutement des gènes de résistance aux antibiotiques". Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24374/24374.pdf.
Pełny tekst źródłaZeitouni, Salman. "Le coût biologique de la résistance aux antibiotiques chez Campylobacter". Rennes 1, 2011. http://www.theses.fr/2011REN1S113.
Pełny tekst źródłaResistance to fluoroquinolones (FQ) or macrolides (MAC) in Campylobacter is a main concern for human campylobacteriosis. This study aimed to determine the consequences resulting from FQ or MAC resistance in C. Coli or C. Jejuni in the absence of antibiotic selection pressure. Resistance to FQ via C257T mutation in the gyrA gene is stable and induces a fitness cost during pairwise competition between the susceptible strain and the resistant mutant. This disadvantage appeared as reduced in vitro growth or survival in food matrices as well as by a less competitiveness during in vivo colonization (in chicken digestive tract) for C. Coli and C. Jejuni. MAC resistance induces an in vitro fitness cost in C. Coli and C. Jejuni. However, in food matrices and in animals, fitness cost was observed only for C. Jejuni. Nevertheless, resistant clones of C. Jejuni harboring double mutations in domain V of 23Sr RNA can appear in colonized chickens and theses evolved mutants showed similar capacity in animal colonization. Acquisition of mutations conferring FQ or MAC resistance enhances invasion capacity of human Caco-2 cells, but has rarely an impact on cytotoxicity. However, if these mutations reduce bacterial motility, resistant mutants can not show any significant enhancement in cells invasiveness comapred to susceptible strains. This work documents the impact of antibiotic resistance on different important characteristics of Campylobacter (survival in food matrices, in vivo colonization, virulence) in order to better understand the strategy of antibiotic restricting prescribing
Dialahy, Isaora Zefania. "Trois essais en analyse bioéconomique de la résistance aux antibiotiques". Doctoral thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/28268.
Pełny tekst źródłaThis thesis adds to the literature of population health by taking an economic perspective. Specifically, it focuses on the bioeconomic analysis of antibiotic resistance. It addresses the socioeconomic issues of the inter-temporal use of antibiotics by considering treatment efficacy of an antibiotic as a renewable or non-renewable resource. Our analysis informs the scientific debate on the parsimonious, effective and sustainable management of available antibiotics. This type of management now appears as a viable alternative to the limited ability of the market to offer new antibiotics capable of dealing with resistant bacteria. We combine (1) an epidemiological approach, which allows the modelling of the transmission of infectious diseases and antibiotic efficacy treatment, and (2) an economic approach, which consists in modelling the demand for antibiotics as well as the private and socially optimal treatment rate of antibiotics. This thesis is organized in three essays. The first essay (Chapter I) focuses on the dynamic analysis of a physician’s prescription rate/ use of antibiotics in a context of bacterial resistance. We compare the physician’s treatment of medical treatment with the socially optimal treatment rate. We postulate a model with a representative physician who treats the population with a single antibiotic. The demand for antibiotics depends on the fraction of individuals willing to pay for the treatment given a prevailing level of antibiotic resistance. The physician's instant utility depends on the income from his work and the level of his/her altruism towards the population welfare. Under these hypotheses, the results show a strong incentive to prescribe the antibiotic when the physician is altruistic and receives a fixed remuneration at all times. In this case, the physician gives priority to healing patients and overuses the antibiotic, accelerating therefore the effect of bacterial resistance. This is not the case when the physician is paid via a fee for services, he/she underutilizes the antibiotic in the short and medium term. By prescribing the antibiotic less, he/she anticipates that an increase in infection will increase his/her remuneration in the future. The second essay (Chapter II) analyzes the demand of the antibiotics available under open access (generic industry) when two antibiotics are available. The epidemiological model developed for this purpose shows an interaction between the reservoirs of treatment efficiency. The interaction functions specified here may have a positive (mutualism) or unfavourable (predation) effect on the evolution of antibiotic treatment efficiencies. Simulation results show that patients first use the antibiotics with the high quality-cost ratio (relative quality) and the greatest additional recovery rate. This advantage tends to decrease under the effect of rising bacterial resistance while the treatment efficiency of the substitute antibiotic increases. Patients will then use both antibiotics simultaneously. This substitution effect is in particular favoured by the positive interaction between the treatment efficiencies. At steady state, this mutualism effect disappears and only one of the antibiotics (depending on the bio-economic parameters) will be used. The third essay (Chapter III) examines the optimal order of the use of antibiotics from social point of view. The goal of the social planner is to maximize the aggregate welfare of the population, including that of healthy individuals. The social cost of using an antibiotic includes pharmaceutical production costs, the external costs of treatment related to antibiotic resistance and the risk of contagion. The results of the analysis show that the antibiotics should be used in sequential order when one antibiotic dominates the other in terms of relative quality (social quality-cost ratio) and net quality (social quality-cost difference). On the other hand, both antibiotics should be used simultaneously when one dominates in terms of relative quality and the other in terms of net quality.
Corpet, Denis. "Résistance aux antibiotiques des bactéries intestinales de l'homme : origine non-iatrogène". Paris 11, 1988. http://www.theses.fr/1988PA114829.
Pełny tekst źródłaChollet, Renaud. "Régulation génétique de la multirésistance aux antibiotiques chez Enterobacter aerogenes". Aix-Marseille 2, 2004. http://www.theses.fr/2004AIX20659.
Pełny tekst źródłaEnterobacter aerogenes is a nosocomial pathogen associated with high mortality rate in intensive care units. Besides the presence of an extended b-lactamase (ESBL) and a chromosomal derepressed cephalosporinase, 5% of clinical isolats show a MultiDrug Resistant (MDR) phenotype. Our work showed that E aerogenes gathers on its genome two systems of MDR regulation: the marRAB and the ramA gene. The two regulators RamA and MarA allow E aerogenes to control exchanges with the external medium and to answer effectively against aggressions. MarA and RamA are able to negatively down-regulate porin expression and to activate the expression of the AcrAB-TolC efflux pump
Siebert, Claire. "Caractérisation moléculaire de la résistance de F.tularensis aux fluoroquinolones". Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAV025/document.
Pełny tekst źródłaIn recent experiments performed in the lab, F. tularensis strains were exposed to increasing concentrations of antibiotics. During this evolution procedure, bacteria acquired a high-level fluoroquinolone (FQ) resistance. This resistance has been associated with mutations in the FQ target genes encoding DNA gyrase and topoisomerase IV. Interestingly, the sequencing of the genomes of these strains showed that exposure to FQ also induced mutations in the gene encoding the FupA protein. My goal is to investigate the putative role of FupA in FQ resistance, an effect never previously reported. Two main approaches will be carried out. 1- phenotypic analysis of fupA mutants: This analysis will consist in complementation of mutants, evaluation of MIC and in vitro study of intracellular multiplication. Previously, the complementation vectors required will be cloned and sequenced. FQ resistance will also be evaluated on a FupA KO Francisella strain to be constructed. 2- biochemical study of the protein: We will perform cloning and purification of the full-length recombinant protein or truncated forms. Recombinant target will be useful for further identification of potential ligands by pull-down experiments. It will also be used to generate antibodies to check expression of FupA in highly resistant clones as well as for IF or EM localisation of the protein. Crystallographic study of this protein is also envisaged
Hernould, Mathieu. "Recherche d'un système d'efflux multidrogue chez Aeromonas hydrophila : impact sur la résistance aux antibiotiques". Bordeaux 2, 2007. http://www.theses.fr/2007BOR21498.
Pełny tekst źródłaDuring the last decade, Aeromonas hydrophila has been shown to be an opportunistic pathogen. In Gram-negative bacteria, the efflux pumps play a major role in the development of the multi-drug resistance phenotype (MDR). This work demonstrated for the first time the funtional analysis of an efflux system of the resistance-nodulation-cell division (RND) type in the genus Aeromonas Inactivation and complementation experiments have shown that AheABC efflux mechanism is responsible for the intrinsic resistance to 13 antimicrobials in the 7966T reference strain. It is noteworthy that the system has nevertheless a narrower spectrum than its homologous in E. Coli as it doesn't include the quinolones antibiotics. The AheR protein interacts with the promoter sequence of the AheABC operon and would be involved in the specific regulation. Furthermore, the finding of a "marbox" motif in this region and an E. Coli Rb-like global activator together implies a global regulation. In addition, the presence of other various pumps in this species has been confirmed by the use of PAβN (Phe-Arg-βnaphthilamide) which is an inhibitor of efflux pumps. Analysis of the activity of PABN on 10 Aeromonas strains from environmental and clinical sources has shown that the AheABC syqtem and other pumps play an important role in the resistance phenotype exhibited by these strains. Regarding the genetic basis of the mechanisms of resistance to quinolones in these strains we have shown that in addition to efflux pumps activity, mutations in the quinolone resistance determining region (QRDR) are also involved in the overall resistant phenotype
Coumes, Florens Stéphanie. "Les modules de " détéction/résistance " aux antibiotiques peptidiques chez les Firmicutes". Phd thesis, Université de la Méditerranée - Aix-Marseille II, 2011. http://tel.archives-ouvertes.fr/tel-00626194.
Pełny tekst źródłaBornet, Charléric. "Perméabilité membranaire et mécanismes de résistance aux antibiotiques chez Enterobacter aerogenes". Aix-Marseille 2, 2004. http://www.theses.fr/2004AIX20654.
Pełny tekst źródłaBiswas, Silpak. "Support moléculaire de la résistance aux antibiotiques chez les bactéries intracellulaires". Aix-Marseille 2, 2008. http://www.theses.fr/2008AIX20658.
Pełny tekst źródłaCoumes, Stéphanie. "Les modules de "détection / résistance " aux antibiotiques peptidiques chez les firmicutes". Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX22062/document.
Pełny tekst źródłaSignal transduction systems and ABC transporters often contribute jointly to adaptive bacterial responses to environmental changes. In Bacillus subtilis, three such pairs, thereafter called modules, are involved in responses to antibiotics: BceRSAB, PsdRSAB and YxdJKLM. They are characterized by a histidine kinase belonging to the Intramembrane Sensing – Histine Kinase family (IM-HK) and by a Membrane Spanning Domain (MSD) possessing an unusually large extracytoplasmic loop. Using a phylogenomic approach we were able to demonstrate that such modules, associating a phosphorelay and an ABC transporter, are specific but widespread in Firmicutes where they originated. This analyse highlight a highly dynamic evolutionary history involving numerous horizontal gene transfers, duplications and lost events, leading to a great variety of Bce-like module repertories in members of this bacterial phylum. Based on fine phylogenetic analyses, the Bce-like modules were divided into six well-defined subfamilies. Functional studies were performed on some members of subfamily IV comprising the bacitracin resistance module BceRSAB of B. subtilis, the expression of which being found to require, in the presence of bacitracin, the signal transduction system as well as the ABC transporter itself. The present results indicate that two other members of subfamily IV, YtsCD of B. licheniformis and BceAB of B. halodurans, were also found to participate in bacitracin resistance processes. The results also suggest that in these modules the ABC transporter works as the first sensor of the antibiotic and that it then activates the signal transduction system through an interaction between one of the two ABC transporter domains and the module kinase.Bacitracin dependent expression of bceAB and bacitracin resistance processes were shown to require the presence of the BceB translocator loop suggesting a crucial role for this loop as well at a functional level, as at a structural level.This study suggests that the original BceRSAB module regulatory mechanism might be generalised to other modules and would constitute an important common antibiotic resistance mechanism in Firmicutes which comprise many human pathogens
Nawfal, Dagher Tania. "Etude épidémiologique de la résistance aux antibiotiques d'isolats cliniques au Liban". Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0661/document.
Pełny tekst źródłaInfections due to multidrug-resistant gram-negative bacteria especially the resistance to carbapenems, have become a major public health problem. This increase in resistance to antibiotics has led to the resuscitation of colistin, as a last-resort treatment option. Our PhD work focused on the epidemiological study of the antibiotic resistance of clinical isolates in Lebanon. This thesis is divided into 5 chapters with three main objectives; (1) the investigation of carbapenem-resistant bacteria in Lebanese hospitals. (2) the Elucidation of the molecular mechanisms of colistin-resistant bacteria in Lebanese patients, and (3) the emergence of vancomycin-resistant gram-positive bacteria in Lebanon. At the start of this thesis, we have prepared a literature review on the epidemiology and the risk factors associated with bacterial infection in conflict wounded and natural disaster in Asia and the Middle East. The second chapter aimed to see the effect of the shift of treatment from colistin-carbapenem combination to colistin monotherapy on the prevalence and resistance of A. baumannii, in addition to the detection of the plasmid-encoded blaVIM-2 gene. In the third chapter, we have detected the spread of colistin-resistant gram-negative bacteria due to mutation of the two-component systems (pmrA /pmrB, phoP/phoQ), or mgrB. We detect the emergence of vanA of Enterococcus faecium resistant to vancomycin. This observation confirms that colistin resistance in Gram-negative bacteria is indeed increasing. In conclusion, it appears necessary and urgent to set up surveys to monitor the use of antibiotics to prevent the spread of resistant strains in Lebanon
Fassi, Fehri Lina. "Activité antimicrobienne de peptides membranotropes et mécanisme de résistance chez mycoplasma pulmonis". Rennes 1, 2005. http://www.theses.fr/2005REN1S061.
Pełny tekst źródłaCagnon, Christine. "Etude des résistances aux antibiotiques glycopeptidiques par mutagenèse dirigée". Toulouse, INSA, 1991. http://www.theses.fr/1991ISAT0012.
Pełny tekst źródłaEl, Garch Farid. "Résistance non enzymatique aux aminosides chez Pseudomonas aeruginosa". Besançon, 2006. http://www.theses.fr/2006BESAA001.
Pełny tekst źródłaPseudomonas aeruginosa is an opportunistic pathogen responsible for chronic lung infection in patients with cystic fibrosis. Ln order to identify aminoglycoside resistance mechanisms, an insertional library was built in reference strain PAO 1 of P. Aeruginosa with a transposon. Screening of 12,000 clones on agar medium containing gentamicin led to the isolation of four groups of aminoglycoside resistant mutants showing either an alteration of the LPS, a defective electron transport chain, a lack in ribosomal protein L25, or overproduction of the efflux system MexXY. Each of these mechanisms promoted a 2-fold increase in the MICs of various aminoglycosides compared to PAO1. When combined, these alterations had addictive or multiplicative effects on resistance to aminoglycosides, resulting in MICs up to 16 fold higher than in PAO1 for clinical relevant drugs such as tobramycin. Altogether, these results show that high level resistance to aminoglycosides in P. Aeruginosa may result from the interplays of several low-level resistance mechanisms
Horgen, Lionel. "Etude des mycobactéries dans la région Antilles-Guyane : épidémiologie moléculaire, résistance aux antibiotiques et interactions bactéries-macrophages". Université de Marne-la-Vallée, 1998. http://www.theses.fr/1998MARN0036.
Pełny tekst źródłaSerra, Fiona. "Antibiothérapie et glycochimie : une nouvelle voie d’accès aux structures de type lincosamide". Montpellier 2, 2007. http://www.theses.fr/2007MON20006.
Pełny tekst źródłaPellet, Térence. "Etude pharmacocinétique/pharmacodynamique de l'antibiorésistance dans la flore fécale : impact d'un traitement à la marbofloxacine par voie parentérale continue et pulsée sur l'émergence d'Escherichia coli fécaux résistants aux fluoroquinolones chez le porcelet sevré". Rennes 1, 2006. http://www.theses.fr/2006REN1B069.
Pełny tekst źródłaArcangioli, Marie-Anne. "Evolution de la résistance aux phénicolés chez Salmonella typhimurium d'origine bovine". Lyon 1, 1999. http://www.theses.fr/1999LYO10188.
Pełny tekst źródłaGordon, Laurence. "Résistance aux antibiotiques utilisés en pisciculture chez des indicateurs bactériens isolés de l'environnement dulçaquicole : caractérisation de la résistance au florfénicol chez Aeromonas spp". Nantes, 2007. http://www.theses.fr/2007NANT2035.
Pełny tekst źródłaUsed in all stock farming sectors, antibiotic treatments are paid particular attention in fish farms. Indeed, it is legitimate to question about the contamination by antibiotics and resistant bacteria of the environment which receives effluents of fish farms. The aim of our research was to study the influences of fish farming along a river on the resistance rates, among Aeromonadaceae, against antibiotics used in fish farms. Still rare in fish pathogens, the acquired resistance against florfenicol, an antibiotic of recent use in fish farming, was searched for genetic characterisation. In a general way, the rates of Aeromonas resistant to oxolinic acid, oxytetracycline and the association sulfamethoxazole-trimethoprime, were often increased in the sediments collected immediately down-stream the fish farms and the wastewater treatment plant effluents. This contamination was not always associated with an antibiotic contamination, which was also noticed down-stream some studied fish farms. Florfenicol resistance was rare in the Aeromonas group, as only two resistant clones were isolated, which were shown to diffuse and to be persistent. In an A. Bestiarum clone, florfenicol resistance was due to a conjugative plasmid, which carried a floR gene and other genes coding for resistance to tetracycline, sulfamids and streptomycine, close to an ISCR2 element which may be implicated in their mobility. Results showed first the complementarity of chemical and microbiological methods to evaluate the impact of antibiotics use in aquatic environment, and secondly that conditions are fulfilled for the spread of acquired florfenicol resistance, which should therefore be surveyed
Barraud, Olivier. "Intégrons de résistance et pression de sélection antibiotique". Limoges, 2011. https://aurore.unilim.fr/theses/nxfile/default/c59be1d0-5b50-4d70-94ea-c8c11bd04c23/blobholder:0/2011LIMO310N.pdf.
Pełny tekst źródłaIntegrons are bacterial genetic elements able to capture and express genes embedded within cassettes. Integrons are widely distributed notably among Gramnegative bacteria (GNB). Resistant integrons (RI) are involved in medical bacteriology due to their ability in recruiting and expressing genes encoding resistance to antibiotics. Aim of this work was to better understand the effect of antibiotic selective pressure on RI working both on a mechanistic level concerning gene cassette rearrangements and on an epidemiological level concerning the link between antibiotic selective pressure and digestive carriage of RI. First part of the work concerned experimental assays of antibiotic selective pressure on an Escherichia coli strain harboring a RI with 4 gene cassettes; second part first consisted in the development of a qPCR method to detect RI, and secondly detected RI in complex environments submitted to antibiotic selective pressures (stools of inpatients, bacteria isolated from hospital effluent or from clinical origin) with focus on the link between RI and antibiotic resistance so as to evaluate the predictive value of RI as biomarkers. Concerning fundamental work, we demonstrated, in our model, that integrase was able, without overexpression, to catalyze gene cassettes rearrangements so as to confer to the host bacteria a higher resistance against the antibiotic selective pressure. Epidemiological work leads to describe new RI among bacteria and showed an effect of antibiotic selective pressure on RI carriage. The link between RI and resistance to antibiotics was confirmed. RI could constitute a hopeful marker of antibiotic resistance in GNB, particularly if considering its negative predictive value
Basmaci, Romain. "Analyse génétique de l'espèce Kingella Kingae : phylogénie, physiopathologie et résistance aux antibiotiques". Paris 7, 2014. http://www.theses.fr/2014PA077155.
Pełny tekst źródłaKingella kingae is a normal agent of the oropharyngeal microbiota and the first pathogen of osteoarticular infections (OAI) in young children. We aimed to characterize the genetic organization of the species and to better understand the pathophysiology of K. Kingae infections and the epidemiology of the antibiotic resistance. We collected 324 isolates from intercontinental origin and developed a multilocus sequence typing schema revealing a large genetic diversity of the species. Five sequence type complexes were predominant and intercontinentally distributed, of which certain were associated with a clinical syndrome, such as OAI or endocarditis. Moreover, development of an animal model highlighted that some strains had different profiles of virulence. Throat samples during K. Kingae OAI confirmed that the oropharynx is the portal of entry for this pathogen and showed that viral infection, especially with human rhinovirus, was significantly associated with them. The rare beta-lactamase producing strains had a clonai distribution and the same clone was present in the USA and Iceland. We isolated the first beta-lactamase producer in continental Europe with the first chromosomal location of the biarEm_i gene. We described the phylogeny of the species and attempted to correlate the genotype with the clinical origin and the experimental virulence of the strains. The tools that we developed combined with the future sequencing of targeted strains would allow identifying new virulence factors to better understand the pathophysiology of K. Kingae. The epidemiology of the antibiotic resistance within this species suggests the risk of emergence of beta-lactamase producing strains
Richard, Matthias. "Mécanismes de régulation impliqués dans la résistance aux antibiotiques chez Mycobacterium abscessus". Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT066.
Pełny tekst źródłaMycobacterium abscessus is an environmental non-tuberculous mycobacteria causing severe lung infections in cystic fibrosis patients. Its intrinsic resistance to antibiotics renders treatments extremely challenging. This pathogen has developed a wide panel of strategies to resist to antibiotics, including efflux pumps and target-modifying enzymes. Standard antibiotherapy combines an aminoglycoside (amikacin (AMK)), -lactams (imipenem (IPM)) and macrolides (clarithromycin (CLR) or azithromycin (AZM)). My thesis was focusing on the regulation of antibiotic resistance mechanisms involving efflux pumps from the MmpL family as well as an enzyme modifying the macrolide target. Selection of resistant mutants against thiacetazone derivatives (TACd) and clofazimine (CFZ) unraveled mutations in the TetR regulators MAB_4384 and MAB_2299c, respectively. The CFZ-mutants, also co-resistant to bedaquiline (BDQ), overexpress two distinct MmpS/MmpL, MAB_135c/1134c and MAB_2300/2301 while the TACd mutants overproduce the MAB_4383c/4382c efflux pump. Biochemical, genetic and structural approaches confirmed their involvement in drug resistance mechanisms. MAB_2299c could therefore represent a potential resistance marker to monitor in strains isolated from patients under CFZ/BDQ therapy. The methyltransferase Erm(41) modifies the adenosine 2058 of the ribosomal 23S rRNA, protecting the ribosome from the macrolides. WhiB7 may represent a major actor in inducible resistance, observed in 40% of clinical cases, often leading to treatment failure. We confirmed the role of WhiB7 in this process and showed that inducible resistance occurred also in vivo in the zebrafish model. Our data suggest that AZM is a stronger and faster resistance inducer than CLR in vitro and that both drugs show antagonism with AMK, thus reducing drugs’ efficacy. This work enriched our knowledge regarding both MmpL-mediated and macrolides inducible resistance mechanism against M. abscessus. It also provides new efficient tools to investigate the function of proteins through a novel unmarked gene deletion approach and to rapidly assay new antibiotics to counteract inducible macrolide resistance
Lupien, Andréanne. "Caractérisation génomique et phénotypique de la résistance aux antibiotiques chez Streptococcus pneumoniae". Doctoral thesis, Université Laval, 2015. http://hdl.handle.net/20.500.11794/25726.
Pełny tekst źródłaStreptococcus pneumoniae is a Gram-positive pathogen responsible for pneumonia, bronchitis and otitis media leading to considerable morbidity and mortality among children and adults. The prevalence of resistant and multi-resistant strains increases worldwide impairing antimicrobial treatments toward this bacterium. We characterised resistance to ciprofloxacin (CIP), tetracycline (TC) and tigecycline (TGC) in laboratory-derived resistant mutants and unsusceptible clinical isolates to further our comprehension of resistance mechanisms and potentially uncover new therapeutic and diagnostic targets toward these drugs. The genomic approaches used in this thesis (genome sequencing and DNA transformation) allowed the phenotypic and genotypic characterisation of mutants resistant to three antibiotics. By this approach, the role of parC and gyrA mutations in CIP resistance was confirmed and even extended and it was also possible to determine that S. pneumoniae may select secondary mechanisms of resistance to CIP and TC besides target-site mutations. Acquisition of a mutation in spr1902 is shown to protect the bacteria against oxygen-reactive species induced by CIP. Furthermore, overexpression of the ABC transporter PatA/PatB and mutations in the coding region of this transporter confer low-level resistance to CIP and TC. A link was also established between TC resistance and overexpression of genes involved in the thiamine biosynthesis and salvage pathway in S. pneumoniae TC non-susceptible isolates. Finally, for the first time, the mechanisms of resistance to TGC in S. pneumoniae were described (mutations in ribosomal protein S3 (rpsC; spr0195), S10 (rpsJ: spr0187), 16S ribosomal RNA (rRNA) and a putative 16S rRNA methyltransferase). These confer cross-resistance to first and second generation TCs. This work highlights new markers of antibiotic resistance in S. pneumoniae.
Madec, Stéphanie. "Résistance des bactéries aux antibiotiques à noyau β-lactame : mécanismes et incidences". Brest, 2001. http://www.theses.fr/2001BRES3105.
Pełny tekst źródłaMichalet, Serge. "Mirabilis jalapa L. (Nyctaginaceae) et modulation de la résistance bactérienne aux antibiotiques". Université Joseph Fourier (Grenoble), 2007. http://www.theses.fr/2007GRE10015.
Pełny tekst źródłaThe control of infectious diseases due to multiresistant pathogenic bacteria, is of primary concern for public health worldwide. The emergence rapidity of restistant strains, due to antibiotics mis use among others, prompts pharmaceutical companies to adopt new anti-infective strategies. Among them, the use of efflux pump inhibitors, in association with extruded antibiotics, is a promising approach as this combinatory therapy (antibitioc + resistance inhibitor association) would be a way to extend and/or improve the efficacy of existing agents. Ln this context, the phytochemical study of Mirabilis jalapa Linn. (Nyctaginaceae) led to the isolation of an active compound, namely N-trans-feruloyI4'-O-methyldopamine. Synthesis of derivatives ofthis aromatic amide let us access potent inhibitors, that showed inhibitory activities of the NorA efflux pump of Staphylococcus aureus, comparable to that of the standard alcaloïd reserpine