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Berge, Andreas. "Molecular analysis of Streptococcus pyogenes and its interactions with the human host." Lund : Lund University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/68945123.html.
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Thern, Anette. "Interactions between Streptococcus pyogenes and the human immune system with special reference to C4b-binding protein /." Lund : Dept. of Medical Microbiology, Lund University, 1998. http://catalog.hathitrust.org/api/volumes/oclc/39224761.html.
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Zhang, Meng. "Proteomic analysis of streptococcus pyogenes." Thesis, Northumbria University, 2007. http://nrl.northumbria.ac.uk/842/.
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Streptococcus pyogenes (group A streptococcus, GAS) is a major human Gram-positive pathogen that causes infections that normally occur in the respiratory tract, the skin, the wound, the lung, the bloodstream and/or muscle tissues and result in millions of deaths every year. To cause such infections, S. pyogenes produces a wide range of virulence factors. The destruction of connective tissue and the hyaluronic acid therein plays an important role in pathogenesis. S. pyogenes was propagated in hyaluronic acid rich growth media in an attempt to create a simple biological system that could reflect some elements of the pathogenesis. The growth of bacteria was analyzed in the hyaluronic acid rich media and control media and a proteomic approach was applied to identify those proteins that were differentially expressed by the streptococcal pathogens growing in the different media. The techniques of two dimensional gel electrophoresis and static nanospray mass spectrometry were optimized and proteome maps for S. pyogenes grown in both media were constructed. The differentially expressed proteins by S. pyogenes were identified and analyzed using bioinformatics. Our results showed that several recognized virulence factors of S. pyogenes were upregulated in hyaluronic acid rich media, including the Ml protein, a collagen-like surface protein and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, which has been shown to play important roles in streptococcal pathogenesis. Interestingly, two hypothetical proteins of unknown function were also up-regulated and detailed bioinformatics analysis showed that at least one of these hypothetical proteins is likely to be involved in GAS pathogenesis. It was therefore concluded that this simple biological system provided a valuable tool for the identification of potential streptococcal pathogens virulence factors.
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Siou, GeÌrard Paul Serge. "Streptococcus pyogenes interactions with human tonsils." Thesis, University of Newcastle upon Tyne, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424082.
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Desai, Meeta. "Molecular epidemiological typing of Streptococcus pyogenes." Thesis, Open University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299021.
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Broglia, Laura. "Regulating with ribonucleases in Streptococcus pyogenes." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/21573.
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Bakterien haben eine Vielzahl an Strategien entwickelt, um sich an ständig wechselnde Umweltbedingungen anzupassen, darunter auch post-transkriptionelle regulatorische Mechanismen. Die Genexpression kann hierbei durch gezielten Abbau oder Stabilisierung von RNA durch Ribonukleasen (RNasen) reguliert werden. RNasen weisen je nach Spezies allerdings unterschiedliche Effekte auf Genexpression und bakterielle Physiologie, sowie verschiedene Strategien der Substraterkennung auf. Dies zeigt, dass unser Verständnis des RNA-Abbaus bei weitem nicht vollständig ist.
Ziel dieser Arbeit ist es, die Eigenschaften und Funktionen der endoRNase Y des humanpathogenen Bakteriums Streptococcus pyogenes zu studieren. Um Einblick in Funktion und Spezifität dieser RNase zu gewinnen, wurden deren genomweite Schnittpositionen (“targetome”) mit Hilfe von RNA-Sequenzierung identifiziert. Zur weiteren Analyse des RNase Y-abhängigen RNA-Abbaus wurde dieses Ergebnis mit dem “targetome” der drei 3′-5′-Exoribonukleasen (ExoRNasen) PNPase, YhaM und RNase R verglichen. Schließlich wurden die Anforderungen für die Prozessierung durch RNase Y und deren Rolle in der Regulation von Virulenzgenen in vivo anhand der speB mRNA, die einen wichtigen Virulenzfaktor codiert, untersucht.
Wir konnten in dieser Arbeit zeigen, dass RNase Y Substrate bevorzugt nach einem Guanosin schneidet und dieses Nukleosid essenziell für die Prozessierung der speB mRNA in vivo ist. Obwohl RNase Y die speB mRNA schneidet, unterstützen die Daten ein Modell nach dem RNase Y die Expression von speB auf transkriptioneller Ebene reguliert. Mit Hilfe des “targetome”-Vergleichs konnten wir ferner zeigen, dass RNase Y den RNA-Abbau in S. pyogenes initiiert und die dabei generierten 3′-Enden der RNA hauptsächlich von den 3′-5′-exoRNasen PNPase und/oder YhaM prozessiert werden.
Zusammenfassend erweitern diese Erkenntnisse unser Verständnis der Funktionalität von RNase Y und des RNA-Abbaus in Gram-positiven Bakterien.Bacteria have developed a plethora of strategies to cope with constantly changing environmental conditions, including post-transcriptional regulatory mechanisms. With this regard, regulation of gene expression can be achieved by either the rapid removal or stabilization of RNA molecules by ribonucleases (RNases). RNases exhibit species-specific effects on gene expression, bacterial physiology and different strategies of target recognition, indicating that our understanding of the RNA degradation machinery is not yet complete. The aim of this thesis was to investigate the features and functions of endoRNase Y from the strict human pathogen Streptococcus pyogenes. To gain insight into the role and specificity of this RNase, we identified RNase Y cleavage positions (i.e. targetome) genome-wide by RNA sequencing. Next, to investigate the RNA degradation pathway depending on RNase Y, we compared the RNase Y targetome with the ones of the three 3′-to-5′ exoribonuclease (exoRNases), namely PNPase, YhaM and RNase R. Finally, to dissect the requirements for RNase Y processing and to decipher the role of RNase Y in virulence gene regulation, we studied the impact of RNase Y on speB mRNA, encoding a major virulence factor. This study reveals that RNase Y preferentially cleaves RNAs downstream of a guanosine and for the first time we were able to show that the presence of a guanosine residue is essential for the processing of speB mRNA, in vivo. Although RNase Y cleaves the speB mRNA, our data underpin a model in which RNase Y-mediated regulation of speB expression occurs at the transcriptional level. Using the targetome comparative approach, we demonstrated that RNase Y initiates RNA decay in S. pyogenes and that the RNase Y-generated RNA 3′ ends are usually further trimmed by PNPase and/or YhaM. Overall, these findings increase our understanding of RNase Y functionality and RNA degradation in Gram-positive bacteria.
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Becherelli, Marco <1979>. "Functional characterization of Streptococcus pyogenes pili." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/3015/1/Becherelli_Marco_Tesi.pdf.
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Group A Streptococcus is a Gram-positive human pathogen able to colonize both upper respiratory tract and skin. GAS is responsible for several acute diseases and autoimmune sequelae that account for half a million deaths worldwide every year (Cunningham et al., 2000). As other bacteria, GAS infections requires the capacity of the pathogen to adhere to host tissues and to form cell aggregates. The ability to persist in distinct host niches like the throat and the skin and to trigger infections is associated with the expression of different GAS virulence factors. GAS pili has been described as important virulence factors encoded by different FCT-operon regions. Based on this information, we decided to study the possible effect of environmental conditions that could regulate the pili expression. In this study we reported the influence of pH environment variations in biofilm formation for strains pertaining to a panel of different GAS FCT-types. The biofilm formation was promoted, excepted in the FCT-1 strains, by a changing in pH from physiological to acidic condition of growth in in vitro biofilm assay. By analyzing the possible association between biofilm formation and pH dependence, we have found that in FCT-2 and FCT-3 strains, the biofilm is promoted by pH reduction leading to an increase of pili expression. These data confirmed a direct link between pH dependent pilus expression and biofilm formation in GAS. As pili are a multi component structure we decided to investigate the functional role of one of its subunits, the AP-1 protein. AP-1 is highly conserved through the different FCT-types and suggests a possible essential role for the pili function. We focused our attention on the AP-1 protein encoded by the FCT-1 strains (M6). In particular this AP-1 protein contains the von Willebrand Factor A (VWFA) domain, which share an homology with the human VWFA domain that has been reported to be involved in adhesion process. We have demonstrated that the AP-1 protein binds to human epithelial cells by its VWFA domain, whereas the biofilm formation is mediated by the N-terminal region of AP-1 protein. Moreover, analyzing the importance of AP-1 in in vivo experiments we found a major capacity of tissue dissemination for the wild-type strain compared to the isogenic AP-1 deletion mutant. Pili have been also reported as potential vaccine candidates against Gram positive bacteria. For these reason we decided to investigate the relationship between cross reaction of sera raised against different GAS and GBS pilin subunits and the presence of a conserved Cna_B domain, in different pilin components. Our idea was to investigate if, using pilus conserved domains, a broad coverage vaccine against streptococcal infection could be possible.
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Becherelli, Marco <1979>. "Functional characterization of Streptococcus pyogenes pili." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/3015/.
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Group A Streptococcus is a Gram-positive human pathogen able to colonize both upper respiratory tract and skin. GAS is responsible for several acute diseases and autoimmune sequelae that account for half a million deaths worldwide every year (Cunningham et al., 2000). As other bacteria, GAS infections requires the capacity of the pathogen to adhere to host tissues and to form cell aggregates. The ability to persist in distinct host niches like the throat and the skin and to trigger infections is associated with the expression of different GAS virulence factors. GAS pili has been described as important virulence factors encoded by different FCT-operon regions. Based on this information, we decided to study the possible effect of environmental conditions that could regulate the pili expression. In this study we reported the influence of pH environment variations in biofilm formation for strains pertaining to a panel of different GAS FCT-types. The biofilm formation was promoted, excepted in the FCT-1 strains, by a changing in pH from physiological to acidic condition of growth in in vitro biofilm assay. By analyzing the possible association between biofilm formation and pH dependence, we have found that in FCT-2 and FCT-3 strains, the biofilm is promoted by pH reduction leading to an increase of pili expression. These data confirmed a direct link between pH dependent pilus expression and biofilm formation in GAS. As pili are a multi component structure we decided to investigate the functional role of one of its subunits, the AP-1 protein. AP-1 is highly conserved through the different FCT-types and suggests a possible essential role for the pili function. We focused our attention on the AP-1 protein encoded by the FCT-1 strains (M6). In particular this AP-1 protein contains the von Willebrand Factor A (VWFA) domain, which share an homology with the human VWFA domain that has been reported to be involved in adhesion process. We have demonstrated that the AP-1 protein binds to human epithelial cells by its VWFA domain, whereas the biofilm formation is mediated by the N-terminal region of AP-1 protein. Moreover, analyzing the importance of AP-1 in in vivo experiments we found a major capacity of tissue dissemination for the wild-type strain compared to the isogenic AP-1 deletion mutant. Pili have been also reported as potential vaccine candidates against Gram positive bacteria. For these reason we decided to investigate the relationship between cross reaction of sera raised against different GAS and GBS pilin subunits and the presence of a conserved Cna_B domain, in different pilin components. Our idea was to investigate if, using pilus conserved domains, a broad coverage vaccine against streptococcal infection could be possible.
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McNamara, Case W. "Molecular analysis of Streptococcus pyogenes M1 protein." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3230034.
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Thesis (Ph. D.)--University of California, San Diego, 2006.Title from first page of PDF file (viewed November 17, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Dixon, Emma Victoria. "Mechanisms of immunoglobulin deactivation by Streptococcus pyogenes." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:ec80e3f9-0c73-4d39-bc68-c39b927365d4.
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The bacteria Streptococcus pyogenes produces a multitude of proteins which interact with and alter the functions of the host immune system. Two such proteins, Endoglycosidase S (EndoS) and Immunoglobulin G-degrading enzyme from S. pyogenes (IdeS) are able to specifically alter the effector functions of immunoglobulin G (IgG). EndoS is a glycoside hydrolase which removes the conserved N-linked glycan from IgG Fc whereas IdeS is a cysteine protease that cleaves the exible protein hinge of IgG. The activity of both proteins results in the reduced ability of IgG to elicit immune responses through Fc receptor binding and complement activation. Amongst other applications, both EndoS and IdeS are actively being explored as new therapeutics for IgG-mediated autoimmune diseases. Given the therapeutic potential of EndoS and IdeS, experiments were designed to investigate the structural and functional characteristics of these enzymes in an effort to understand their specficity for and activity against IgG. Here, bioinformatic and biophysical characterisation of EndoS identified subdomains outside of the catalytic domain which contribute to glycoside hydrolase activity. The substrate specificity of EndoS was also explored and showed that EndoS hydrolyses a broad range of glycans from the IgG scaffold. EndoS was also shown to have activity against alternative glycoprotein substrates, however, this non-specific activity was negligible in the context of whole serum. The effect of EndoS-mediated deglycosylation on the structure of the IgG Fc domain was explored using both X-ray crystallography and small-angle X-ray scattering. Small angle X-ray scattering was also used to characterise both EndoS and IdeS in complex with IgG Fc. Solution-state models of each complex were produced providing preliminary data towards how these enzymes interact with IgG. Overall, the results presented here contribute to our understanding of these enzymes which is of importance as they go forward into clinical applications.
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Caswell, Clayton Christopher. "The SCL1 protein of Streptococcus pyogenes a structure-function analysis /." Morgantown, W. Va. : [West Virginia University Libraries], 2008. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=6026.
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Thesis (Ph. D.)--West Virginia University, 2008.Title from document title page. Document formatted into pages; contains xi, 190 p. : ill. (some col.). Includes abstract. Includes bibliographical references.
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Darenberg, Jessica. "Streptococcus pyogenes infections and toxic shock syndrome : molecular epidemiology and immunotherapy /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-676-X/.
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Meinhart, Anton. "Kristallstrukturanalyse des e, z-Proteinkomplexes [Epsilon, zeta-Proteinkomplexes], kodiert vom Plasmid pSM19035 aus Streptrococcus pyogenes." [S.l.] : [s.n.], 2001. http://www.diss.fu-berlin.de/2001/188/index.html.
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Luis, Philippe Renard Vincent. "Le TDR modifie-t-il la pratique des médecins généralistes d'Ile de France ?" Créteil : Université de Paris-Val-de-Marne, 2006. http://doxa.scd.univ-paris12.fr:80/theses/th0240166.pdf.
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Russell, Hugh Hayden. "Molecular basis of epithelial internalisation of Streptococcus pyogenes." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423540.
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Le, Rhun Anaïs. "Multifaceted RNA-mediated regulatory mechanisms in Streptococcus pyogenes." Doctoral thesis, Umeå universitet, Molekylär Infektionsmedicin, Sverige (MIMS), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-111090.
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Bacterial pathogens rely on precise regulation of gene expression to coordinate host infection processes and resist invasion by mobile genetic elements. An interconnected network of protein and RNA regulators dynamically controls the expression of virulence factors using a variety of mechanisms. In this thesis, the role of selected regulators, belonging to the class of small RNAs (sRNAs), is investigated. Streptococcus pyogenes is a pathogen responsible for a wide range of human diseases. Genome-wide screenings have indicated that S. pyogenes encodes numerous sRNAs, yet only a limited number have been characterized. A major goal of this study was to identify and characterize novel sRNAs and antisense RNAs (asRNAs) using RNA sequencing analysis. We validated 30 novel sRNAs and asRNAs, and identified 9 sRNAs directly cleaved by the ribonucleases RNase III and/or RNase Y. Previous work from the laboratory has highlighted the role of sRNAs from the type II Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas) systems in S. pyogenes. CRISPR-Cas systems provide adaptive immunity to prokaryotes against infection by mobile genetic elements. Two sRNAs, forming a complementary duplex (dual-RNA), are effectors of this system: the mature CRISPR RNAs (crRNAs) and the trans-activating crRNA (tracrRNA). The dual-RNA guides the Cas9 endonuclease to cleave both strands of the invading DNA in a sequence-specific manner. This RNA-programmable CRISPR-Cas9 system is now utilized for genome editing and engineering in a wide range of cells and organisms. To expand the potentialities of this tool, we both, searched for Cas9 orthologs and predicted numerous tracrRNA orthologs. We defined tracrRNA as a new family of sRNAs sharing the ability to base-pair to cognate crRNAs, without conservation of structure, sequence or location. We show that Cas9 and the dual tracrRNA:crRNAs are only interchangeable between closely related type II CRISPR-Cas systems. In summary, this thesis presents new insights into RNA-mediated regulatory mechanisms in S. pyogenes. We identified and described the expression of novel sRNAs, highlighting potential antisense RNAs. Focusing on the dual-RNA programmable type II CRISPR-Cas system, we provided evidence for co-evolution of the Cas9 enzyme with tracrRNA:crRNA, a basis for Cas9 multiplexing in genome editing.
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Sethman, Chad Robert. "Attachment of Streptococcus pyogenes to Host Epithelial Cells." Miami University / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=miami1071776892.
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Tedde, Vittorio. "Zinc uptake in Streptococcus pyogenes: characterisation of adcA." Doctoral thesis, Università degli studi di Padova, 2012. http://hdl.handle.net/11577/3422118.
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Streptococcus pyogenes (also known as Group A Streptococcus, GAS) is a capsulated Gram-positive, human-adapted pathogen. GAS strains express different virulence factors exposed on the bacterial surface or secreted outside the cell. Among the secreted virulence factors, superantigens (SAGs) are certainly the most toxic factors. A recent study demonstrates that, in vitro, the streptococcal superantigen SpeI interacts with AdcA and Lmb, the substrate binding subunits of the two zinc transporters. In particular, AdcA belongs to the high-affinity zinc transporter Adc, involved in adhesion, competence and zinc uptake. Zinc is an essential micronutrient for all living organisms but cells have to tightly control its intracellular concentration due to its toxicity.
In this thesis the role of adcA in zinc uptake in GAS was studied. Three independent ΔadcA null mutants were generated in the strain MGAS5005, and their phenotype was characterised. The mutants were obtained by means of the low copy number temperature-sensitive shuttle vector pJRS233. Deletion of the adcA gene in Streptococcus pneumoniae leads to a dramatic decrease in competence. Thus, complementation using the pMU1328 plasmid was obtained by transforming the intermediate strain MGAS5005::pJRS233-ΔadcA that still contains the wild type adcA allele.
The absence of a zinc transporter affects the capacity to uptake zinc from the culture medium and the mutant susceptibility to zinc starvation. The Δadca null mutants clearly displayed a higher sensitivity to zinc starvation compared to the wild type strain. The complementation of one of the mutants with the wild type gene restored the phenotype. When the ΔadcA mutant is grown in the presence of the zinc chelator TPEN, growth is rescued both by zinc or manganese. This probably means that the import of these two metals is carried out by the other zinc transporter Lmb, coded within the operon lmb-htpA. Hence, the expression of Lmb and HtpA was analysed by Western blot in different growth conditions. In wild type cells AdcA is always expressed at a high level, whereas Lmb and HtpA are highly expressed only in zinc-depleted medium or in ΔadcA mutants. This finding supports the notion that AdcA is functionally homologous to ZnuA, the major high affinity zinc transporter in many bacteria, and like ZnuA is responsible for the efficient recruitment of zinc in most conditions.Streptococcus pyogenes (detto anche Streptococco di gruppo A, GAS) è un batterio Gram-positivo capsulato, adattato ad infettare l’uomo. I ceppi di GAS esprimono diversi fattori di virulenza che possono essere esposti sulla superficie esterna o secreti fuori dalla cellula. Tra i fattori di virulenza, i Superantigeni (SAGs) sono sicuramente tra i più nocivi per l’ospite. Uno studio recente ha dimostrato che in vitro SpeI, un superantigene secreto da GAS, interagisce con AdcA a Lmb, due proteine che trasportano lo zinco. In particolare, AdcA appartiene al trasportatore ad alta affinità Adc, che è coinvolto nell’adesione, nella competenza e nel trasporto dello zinco. Questo metallo è un microelemento essenziale per tutti gli organismi viventi, ma poiché possiede una elevata tossicità, le cellule devono regolare finemente la sua concentrazione intracellulare. In questo lavoro di tesi è stato studiato il ruolo di AdcA nel trasporto dello zinco in GAS. Per questo studio sono stati generati tre mutanti indipendenti nel ceppo MGAS5005, caratterizzandone il loro fenotipo. I mutanti sono stati ottenuti mediante l’uso del vettore termosensibile pJRS233. La delezione del gene adcA in Streptococcus pneumoniae comporta una notevole diminuzione della competenza, quindi la complementazione è stata ottenuta trasformando il mutante parziale, cioè l’ “eterozigote” intermedio che contiene sia l’allele wild type che quello mutato. L’assenza del trasportatore dello zinco influisce sulla capacità di importare lo zinco dal terreno di coltura e sulla suscettibilità alla mancanza di zinco. I mutanti ΔadcA mostrano chiaramente una maggiore sensibilità alla deprivazione di zinco se comparati con il ceppo wild type. La complementazione di uno dei mutanti riporta il fenotipo del mutante a quello del ceppo wild type. Quando il mutante è cresciuto in presenza di una concentrazione inibente del chelante TPEN, la crescita è ristabilita dalla aggiunta di zinco o di manganese. Questo probabilmente significa che il trasporto di questi due metalli può avvenire tramite l’altro trasportatore Lmb, codificato all’interno dell’operone lmb-htpA. Di conseguenza, l’espressione di Lmb e HtpA è stata analizzata tramite Western blot in condizioni di crescita diverse. Nelle cellule wild type AdcA è sempre espresso ad alti livelli, invece Lmb e HtpA sono espresse ad alti livelli solo nel terreno di coltura depleto di zinco. Questo risultato avvalora il concetto che AdcA è omologo da un punto di vista funzionale a ZnuA, il maggior trasportatore ad alta affinità dello zinco in molti batteri, e come ZnuA ha il compito del reclutamento dello zinco in molte condizioni.
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Smeesters, Pierre. "Epidémiologie, pathogénie et prise en charge des infections à Streptococcus pyogenes touchant les enfants de Bruxelles et de Brasília." Doctoral thesis, Universite Libre de Bruxelles, 2007. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210620.
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Les Streptocoques Béta-hémolytiques du groupe A (GAS) sont responsables de manifestations cliniques variées et de séquelles non suppuratives comme notamment le rhumatisme articulaire aigu (RAA). Les affections sévères à GAS tuent plus de 500.000 personnes chaque année. Le pouvoir pathogène du GAS est encore mal compris. Il semble être notamment lié à la présence de nombreux gènes codant pour des facteurs de virulence dans le génome du GAS, dont celui codant la protéine emm. La protéine transmembranaire M joue un rôle essentiel dans la virulence du GAS. Le typage moléculaire des GAS se base sur la séquence de la partie hypervariable de ce gène (emm-typing). L’épidémiologie du GAS semble varier au cours du temps et en fonction de la localisation géographique et/ou du contexte socio-économique. Cependant, les différences dans les critères d’inclusion des différentes études épidémiologiques disponibles dans la littérature rendent les comparaisons difficiles. Pour mieux évaluer ces variations, nous avons mené une analyse prospective de l’épidémiologie clinique et moléculaire d’isolats de GAS provenant d’enfants présentant une infection à GAS, simultanément en deux localisations géographiques différentes (Bruxelles et Brasília, Brésil).
Un des points importants de notre étude a été la mise en évidence de la diversité génétique de la protéine M des isolats belges et brésiliens. Alors que de nombreux emm-types différents sont retrouvés à Brasília (48 emm-types sur 128 isolats), ceux retrouvés à Bruxelles sont relativement peu nombreux (20 emm-types sur 200 isolats) et sont ceux communément retrouvés dans les pays industrialisés. Afin de mieux comprendre les bases moléculaires de cette différence, une analyse phylogénétique basée sur la quasi-totalité de la séquence de la protéine M exposée à la surface de la bactérie a été réalisée. Cette analyse a permis de montrer que les emm-types belges sont génétiquement éloignés les uns des autres alors que les emm-types brésiliens sont génétiquement plus proches. De manière intéressante, cette analyse a montré que les souches belges présentent une grande diversité au niveau de la région de la protéine M dite ‘constante’. En conséquence, la diversité génétique globale des protéines M belges et brésiliennes est similaire, mais elle se situe dans des régions différentes de la protéine M, ce qui pourrait indiquer l’existence de pressions de sélection différentes entre les deux pays. D’un point de vue vaccinal, ces résultats indiquent qu’un vaccin dirigé contre certaines des parties constantes de M présenterait une bonne couverture théorique dans les deux pays. Par contre, le vaccin 26-valent, en cours d’évaluation clinique, aurait une couverture théorique de 76% à Bruxelles et de 32% à Brasília.
Notre analyse phylogénétique a également permis de montrer que la non-sensibilité à la ciprofloxacine (observée dans 22,5 % et 9% des souches belges et brésiliennes respectivement) survient dans des souches génétiquement éloignées, contrairement à ce qui est proposé actuellement dans la littérature. De plus, nous avons mis en évidence un polymorphisme au sein des gènes codant les topoisomérases cibles de la ciprofloxacine. L’identification de mutations responsables du phénotype de non-sensibilité nécessite par conséquent une confirmation expérimentale.
Les manifestations cliniques sont assez différentes entre Bruxelles et Brasília. Les infections cutanées sont beaucoup plus fréquentes à Brasília. De manière intéressante au Brésil, des souches de GAS présentant un tropisme cutané sont isolées du pharynx. Ces souches ‘cutanées’ pourraient avoir acquis des déterminants génétiques leur permettant de se développer dans des tissus pharyngés. De plus, ces résultats pourraient remettre en question le postulat que seules les souches de tropisme pharyngé sont impliquées dans le développement du RAA. D’autres études épidémiologiques dans des pays où le RAA est endémique devront être réalisées afin de préciser nos résultats et de mieux comprendre les mécanismes moléculaires menant au développement du RAA.
Cependant, étant donné la prévalence du RAA et l’accès limité au diagnostic microbiologique des pharyngites dans le réseau public de soins au Brésil, nous avons développé un score clinique permettant de limiter les traitements antibiotiques chez les enfants probablement atteints de pharyngites virales. L’utilisation de ce score permettrait de réduire le nombre de prescriptions antibiotiques dans les pharyngites de l’enfant de 41 à 55% à Brasília.
Le choc toxi-infectieux est une pathologie relativement rare et le RAA n’est quasi plus décrit dans les pays développés. Cependant, deux nourrissons ont présenté un choc toxi-infectieux suivi d’un RAA (HUDERF, Bruxelles). A notre connaissance, cette association clinique n’a jamais été décrite. L’analyse de ces deux cas du point de vue de la virulence bactérienne a révélé la présence de nombreux gènes de facteurs de virulence, portés par des phages et différents dans les deux souches. Nos résultats illustrent la complexité de la relation hôte-pathogène.
La capacité des bactéries à s’adapter à leurs hôtes et à causer des pathologies dépend de nombreux facteurs, qui varient d’un isolat à l’autre, et dont l’importance varie d’un hôte à l’autre. Notre travail a permis d’exemplifier la diversité génétique des GAS, aussi bien au niveau du gène emm qu’au niveau des facteurs de virulence, et de l’implication de ceux-ci dans le développement de pathologies streptococciques rares.
Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
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Cunningham, Cynthia A. "Induction of myosin cross-reactive antibody and cytolytic T cell responses in mice with Streptococcus pyogenes." Morgantown, W. Va. : [West Virginia University Libraries], 2000. http://etd.wvu.edu/templates/showETD.cfm?recnum=1530.
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Malerba, Mariangela. "The immunomodulatory role of epidermal hepcidin in infectious condition." Thesis, Sorbonne Paris Cité, 2018. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2166&f=13318.
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L'hepcidine, initialement identifiée comme un peptide antimicrobien, s'est révélée être un peptide hormonal clé du métabolisme du fer capable d'inhiber l'absorption intestinale du fer alimentaire et son recyclage par les macrophages. L'expression de l'hepcidine est induite par l’excès de fer mais également en réponse à l' infection/inflammation. L'hepcidine, comme son nom l'indique, est principalement synthétisée par les hépatocytes mais également, à plus faibles niveaux, par d'autres types cellulaires. Notre équipe a démontré que ce peptide hépatique était suffisant pour assurer l'homéostasie systémique du fer en conditions physiologiques suggérant un rôle local de l'hepcidine extra-hépatique en conditions physiopathologiques. L'hepcidine présente une similarité de structure avec les beta-défensines, une sous-famille de peptides antimicrobiens (AMPs). Les AMPs sont de petites protéines ayant des fonctions antimicrobiennes mais aussi immuno-régulatrices. De manière intéressante, nous avons observé une forte similarité de structure entre l'hepcidine humaine et l' IL-8, chimiokine des neutrophiles et démontré que l'hepcidine induit la migration des neutrophiles in vitro. Nous avons confirmé par bioluminescence que l'hepcidine est également capable de recruter des neutrophiles in vivo. Ainsi, de manière surprenante, nous avons décrit une nouvelle fonction immuno-modulatrice de cet AMP. Les épithelia, comme l' intestin et la peau, sont la principale source des AMPs. Or, l'expression de l'hepcidine et son rôle en tant qu'AMP dans ces tissus n'a jamais été investigué. J'ai, au cours de ma thèse spécifiquement étudié le rôle de l'hepcidine dans la peau lors d'une infection sous-cutanée (SC) aux streptocoques de groupe A (GAS). Ces bactéries peuvent coloniser la peau et sont responsables d'une large gamme d'infections cutanées superficielles et invasives. Les AMPs produits par les cellules épithéliales et par les cellules immunitaires circulantes (neutrophiles et macrophages) sont les premières « lignes de défense » contre les GAS. Les infections SC par GAS représentent donc un très bon modèle pour étudier la fonction de l'hepcidine comme peptide antimicrobien dans la peau. Nous avons généré des souris des KO conditionnelles de l'hepcidine dans les kératinocytes (Hepc KOker) et dans les cellules myéloïdes (Hepc KOmyel) et soumis ces souris à des modèles d'infection SC par GAS. Nous avons observé que les souris Hepc KOmyel et WT présentent le même nombre de bactéries au niveau local et au niveau systémique, alors que les souris Hepc KOker sont beaucoup plus sensibles à l'infection que les WT, avec un nombre significativement plus élevé de bactéries au niveau de la lésion et une plus grande dissémination systémique. Nous avons observé que l'hepcidine n'avait ni effet bactériostatique ni bactériolytique contre les GAS in vitro et que les kératinocytes primaires WT et Hepc KOker présentaient la même activité bactéricide. De façon intéressante, nous avons constaté que l'hepcidine stimule la sécrétion de CXCL1, chimiokine des neutrophiles, par les kératinocytes primaires. En accord avec ces résultats, l' expression de CXCL1 et le nombre de neutrophiles recrutés sur le site de l' infection sont plus faibles chez les souris Hepc KOker que chez les WT. De plus, l' injection SC de CXCL1 corrige ces défauts, confirmant que le défaut de production de CXCL1 est responsable de l'infection observée chez les souris Hepc KOker. Enfin, nous démontrons que l' injection d'hepcidine exogène empêche la propagation de l'infection. En conclusion notre travail met en évidence un nouveau rôle protecteur de l'hépcidine épidermique contre l'infection à GAS, à travers la modulation du recrutement des neutrophiles et suggèrent que l'hepcidine pourrait représenter une nouvelle approche pour le traitement des infections à GASHepcidin, first discovered as an antimicrobial peptide, is now considered as the key iron regulatory hormone, inhibiting duodenal iron absorption and iron recycling by macrophages. Hepcidin expression is induced by iron accumulation and infection/inflammation while diminished in situations of iron needs. Hepcidin, as suggested by its name, is mainly expressed in the liver (Hep- for Hepatic) but also at low levels by many other cells. Our team has demonstrated that hepatic hepcidin is sufficient to ensure the systemic iron homeostasis in basal conditions; suggesting that extra-hepatic hepcidin could play local roles in pathophysiological conditions. Hepcidin contains 4 disulfide bonds with β-sheet fold and positively charged residues at the surface, showing close structural similarity to beta-defensins, a subfamily of antimicrobial peptides (AMP). AMPs are small proteins with antimicrobial activities but also immunomodulatory functions (chemotaxis, ...). Because hepcidin possesses disulfide bridges, resembling the intramolecular disulfide bonds critical for the function of chemokine proteins, we investigated the direct chemoattractant potential of hepcidin. We observed that human hepcidin shares structural similarities with the human CXCL1 homologue and demonstrated that hepcidin triggers neutrophil migration in vitro with a bell-shaped dose response curve, characteristic of chemokines. Taking advantage of in vivo bioluminescence assay, we confirmed that SC injection of hepcidin causes neutrophil recruitment in vivo. These results highlight a new immunomodulatory role of this AMP. Epithelia, such as intestine and skin, are the main source of AMPs. However, expression of hepcidin and its functional role as AMP in these tissues has never been studied. Therefore, I specifically investigated this aspect in the skin, using a model of group A streptococcal (GAS) subcutaneous (SC) infection. These gram-positive bacteria commonly colonize skin and are responsible for a wide range of both skin and invasive infections causing more than 500,000 deaths per year. The first host immune effectors encountered by GAS are endogenous AMP produced by epithelial cells and by circulating immune cells (neutrophils and macrophages) so GAS represents a tremendous model to study hepcidin function as antimicrobial peptide in the skin. We specifically deleted hepcidin in keratinocytes (Hepc KOker) and in myeloid cells (Hepc KOmyel). Interestingly, while Hepc KOmyel and WT littermates showed the same number of bacteria at local and systemic level, we found that Hepc KOker mice present a worse outcome after infection than WT littermates, with a significantly higher number of bacteria at the lesion site and a stronger systemic spread of infection. We observed that hepcidin has neither bacteriostatic nor bacteriolytic effect against GAS in vitro and that both WT and Hepc KOker primary keratinocytes displayed the same bactericidal activity. Interestingly, we found that hepcidin promotes keratinocyte secretion of CXCL1, a key neutrophil chemokine, in vitro. Consistently, both the amount of CXCL1 and the number of neutrophils recruited at the site of infection was lower in Hepc KOker mice compared to WT littermates. Moreover, CXCL1 SC injections rescue the phenotype, confirming that the invasiveness observed in Hepc KOker is specifically caused by the absence of hepcidin-mediated CXCL1 production. Finally, we demonstrated that injections of exogenous hepcidin prevents the infection spread. These results highlight a new protective role of epidermal hepcidin against GAS infection, through modulation of neutrophil recruitment and suggest that hepcidin could represent a novel approach for therapy of GAS infections
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Beck, Isabel L. "Tolérance à la pénicilline G de souches de "Streptococcus pyogenes" isolées au cours d'angines aigue͏̈s de l'enfant." Paris 5, 1993. http://www.theses.fr/1993PA05P199.
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Galeas, Pena Trilce Michelle. "Thermoregulation of capsule production of Streptococcus pyogenes strain HSC5 /." Available to subscribers only, 2009. http://proquest.umi.com/pqdweb?did=1967978671&sid=7&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Delgado, Giselle M. "SIAA and Neat2 Heme Binding Proteins from Streptococcus Pyogenes." Digital Archive @ GSU, 2009. http://digitalarchive.gsu.edu/chemistry_theses/24.
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The bacterium Streptococcus pyogenes requires heme, which is taken up via an ABC transporter. An understanding of this pathway may result in new approaches to antibacterial agents. Both SiaA and NEAT2 (NEAr Transporter 2) are proteins involved in heme binding. One of the axial ligands of SiaA, His 229, was purified to study how mutagenesis affects heme binding. UV-visible studies showed a small band at 420 nm with respect to the protein band at 288 nm which probably indicates that heme was lost easily from this mutant. We have also worked to optimize the yield of Shr-NEAT2 by changing different variables. For each of the batches, the yield of holoNEAT2 was calculated by UV-visible spectroscopy. Increasing oxygen during growth did not improve holoNEAT2 yield. On the other hand, lower temperature, decrease in time after induction, and addition of ALA all increased the protein production.
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Calusni, Ana Lucia Roscani. "Interação entre o Streptococcus pyogenes e a hemoglobina S." [s.n.], 1994. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316745.
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Orientador: Antonio Sergio RamalhoDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-07-19T08:31:44Z (GMT). No. of bitstreams: 1 Calusni_AnaLuciaRoscani_M.pdf: 1715301 bytes, checksum: acd3974eacbc813ea7e1416eeec145b7 (MD5) Previous issue date: 1994
Mestrado
Genetica
Mestre em Ciências Biológicas
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LE, BOUGUENEC-BRIVE CHANTAL. "Etude d'un element genetique mobile (tn3701) chez streptococcus pyogenes." Paris 7, 1989. http://www.theses.fr/1989PA077082.
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Mise en evidence chez streptococcus pyogenes d'un element transposable (tn3701) capable de conferer la resistance aux antibiotiques erythromycine, tetracycline et microcycline. Une carte de restriction de la region contenant cet element a ete etablie. Par hybridation moleculaire il a ete possible de reveler une forte homologie entre tn3701 et d'autres elements chromosomiques transferables par conjugaison decrits dans d'autres souches de streptococcus
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Weinstein, Kathryn Elizabeth. "Generation of Diversity During the Survival of Streptococcus pyogenes." Diss., Temple University Libraries, 2010. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/105846.
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Microbiology and ImmunologyPh.D.
Streptococcus pyogenes is a human-specific pathogen that can cause a wide variety of diseases. These diseases range from the relatively mild pharyngitis and impetigo to invasive diseases such as necrotizing fasciitis to post-streptococcal sequelae such as rheumatic heart disease. The bacteria are frequently carried asymptomatically and may cause recurrent disease. Corresponding with their etiologic variation amongst diseases, clinical isolates demonstrate diverse virulence factor expression and random genetic mutations. In these studies, we examine the role of intracellular residence during survival as a niche for the diversification of S. pyogenes. Survival was previously studied using two in vitro systems: long-term stationary phase survival in culture and survival within epithelial cells in the presence of extracellular antibiotics. The surviving populations diversified, giving rise to stable strains with alternate colony morphologies, distinct proteomes, and altered metabolic properties. Further analysis in these studies showed that alterations in colony morphology were not solely observed during survival, but could also be induced in models mimicking acute infection. However, diversification in certain metabolic pathways occurred only during survival, and this metabolic diversification was observed at the transcriptional level. Further, one of three clinical isolates from patients with recurrent pharyngitis was altered in its metabolic profile, suggesting metabolic diversification may be occurring in vivo. The survivor strains had varied transcriptional changes in the genes encoding the virulence factors emm, slo, and speB. All of the stationary phase-derived survivor strains and two intracellular survival-derived strains had attenuated virulence in zebrafish. Most of the attenuated strains disseminated to the spleen and were cleared within three days. A whole blood killing assay showed a strong correlation between bacterial killing and emm expression. While the diversification appeared random, these strains retained their multilocus sequence type (MLST). These results suggest S. pyogenes strains with the same MLST, but diverse virulence properties, may arise during survival in the host.
Temple University--Theses
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Steinberg, Gregory. "Long-term Stationary Phase Behavior of Streptococcus pyogenes Biofilms." Master's thesis, Temple University Libraries, 2012. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/170151.
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Microbiology and ImmunologyM.S.
Long-term Stationary Phase Behavior of Streptococcus pyogenes Biofilms Department of Microbiology and Immunology Streptococcus pyogenes is the etiological agent of many human diseases ranging from mild superficial skin infections and pharyngitis to life-threatening necrotizing fasciitis. There can be several complications as a result of S. pyogenes infection including post-streptococcal glomerulonephritis and rheumatic fever, which leads to rheumatic heart disease. Despite the significant virulence associated with the pathogen, the bacteria can also persist asymptomatically in human host carriers. S. pyogenes is characterized by significant strain-to-strain variation with many single nucleotide polymorphisms and differences in genetic content of up to 33% of the genome. Active infection is associated with the rapid growth of the pathogen, whereas survival or carriage is associated with slow growth. Our laboratory has demonstrated that during survival in long-term stationary phase cultures and in eukaryotic cells, S. pyogenes diversifies into a mixed population. Isolates from this population show diversification in their proteome, in metabolism, and in virulence factor transcription patterns. These are stable, heritable changes with unique mutations in global gene regulators in some isolates, suggesting that an accumulation of genetic mutations leads to diversification. There are two proposed modes of survival in the human host; by taking residence intracellularly in host cells and as biofilms. Previous studies showed that isolates surviving within eukaryotic cells acquire heritable changes in metabolism and virulence factor expression. Biofilms are highly organized structures formed by many bacteria, which provide resiliency to harsh environmental conditions. It has been demonstrated that S. pyogenes form biofilms in vivo and in vitro, and up to 90% of clinical isolates can form biofilms. Considering the resiliency of biofilms, and the organized roles played by individual cells in biofilms, we hypothesized that biofilms may provide S. pyogenes with a niche for persistence and diversification. Despite the capacity for survival of planktonic cells, we have found that viable cells could not be isolated from static biofilms after 10 days. No metabolic variants were found among biofilm isolates prior to loss of biofilm viability. Biofilm structure was examined using confocal microscopy to image cells after LiveDead® staining. These experiments revealed that the biofilms lost viability rapidly, and also appeared to disperse. Dispersion of 2-day old biofilms could be induced with culture supernatants collected from 7-day old planktonic cells. Overall, the results of these studies suggest that secreted factors from late stationary phase cultures induce biofilm dispersion and biofilms do not serve as a niche for long-term survival and diversification of S. pyogenes. Therefore, S. pyogenes biofilms may be more critical for initial colonization of the oropharynx. These studies may provide a valuable insight to the role of biofilms in S. pyogenes infections.
Temple University--Theses
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Galeas, Trilce Michelle. "Thermoregulation of Capsule Production of Streptococcus pyogenes Strain HSC5." OpenSIUC, 2009. https://opensiuc.lib.siu.edu/theses/122.
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Group A Streptococcus (GAS) is responsible for mild and common infections like tonsillitis and pharyngitis, and more serious invasive disorders like necrotizing fasciitis and glomerulonephritis. The ability to invade tissues is closely linked to the virulence factors expressed by the bacterium. Hyaluronic acid capsule expression is variable among all the strains in S. pyogenes and confers the capacity to evade the immune response. In a previous study, it was found that capsule production in CovR mutants was temperature-regulated, showing no capsule production at 37℃ but increased production was observed at 25℃. In this study, the objective is to find the elements involved in the thermoregulation using a genetic approach. First, mutants were created by knocking-out CovR, the response regulator of the CovRS two-component system that controls about 15% of GAS genome. Transposon mutants were screened to find changes in capsular phenotype. Colonies expressing capsule at 37℃ were selected for sequencing. The sequencing revealed three different events in different mutants. Two of them pointed at hypothetical proteins, one of them, SpyM3_1255, was phage associated protein with a DnaD domain and the other one, SpyM3_1377, encoded cvfA. A third over-producer mutant showed an insertion in the promoter area of the has operon, the operon that encodes for hyaluronan synthase production, upstream from other disruptions in the promoter area that generated non-producing mutants. This suggest that there is more than one factor involved in thermoregulation of capsule production.
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Wright, Jordan. "Capsule Thermoregulation and Non-Coding RNA in Streptococcus pyogenes." OpenSIUC, 2014. https://opensiuc.lib.siu.edu/theses/1505.
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Streptococcus pyogenes is a re-emerging pathogen that produces superficial and life threatening invasive diseases. One important virulence factor in S. pyogenes is hyaluronic acid capsule which has been shown to increase expression at sub-body temperatures in certain strains. This study showed that thermoregulation is common in invasive clinical isolates. Regulation was shown to occur independent of the CovRS two-component regulator in a post transcription manner and before protein level regulation. The endoribonuclease, CvfA, was also confirmed to be required for capsule thermoregulation. The search for a regulator lead to the discovery of the 1st antisense RNAs in S. pyogenes found opposite the capsule synthesis genes. Its role if any in capsule has not been discovered. Finally, a group of sRNAs were characterized adding to the knowledge of this layer of regulation in S. pyogenes.
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Johansson, Söderberg Jenny. "The streptococcal IgG degrading enzyme IdeS : studies on host-pathogen interactions." Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-53706.
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The important human pathogen Streptococcus pyogenes causes both mild infections such as pharyngitis and impetigo but also severe life threatening invasive infections. Specific antibodies (IgG) recognize pathogens and are important mediators for pathogen clearance by the immune defence. S.ipyogenes expresses a highly effective and specific IgG endopeptidase called IdeS (immunoglobulin degrading enzyme of S.ipyogenes). IdeS rescues bacteria from opsonising IgG by cleavage of IgG generating two fragments F(ab´)2 and ½Fc. Moreover, IdeS block ROS production by neutrophils. In this thesis I have studied (i) allelic variants of IdeS and their biological potential, (ii) consequences of ½Fc production for host-pathogen interactions and (iii) IdeS processing by streptococcal and neutrophil proteases. When investigating the allelic variants of IdeS we could show that in respect to IgG degradation and inhibition of ROS production the allelic variants where indistinguishable, however the allelic variant of serotype M28 appears to be an unique exception as this protein was deficient in IgG cleavage but still inhibited ROS production. Further, the ½Fc fragments produced when IgG is cleaved by IdeS were shown to prime human neutrophils and under ex vivo experimental conditions this increased the bactericidal activity of the neutrophils. Finally, we made the interesting finding that IdeS is N-terminally processed by neutrophil proteases and by the streptococcal protease SpeB, but retain enzymatic activity and was less immunogenic compared to the full length protein.
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Libkind, Marianna. "SiaA, a heme protein." unrestricted, 2006. http://etd.gsu.edu/theses/available/etd-02192007-092252/.
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Thesis (honors)--Georgia State University, 2006.Title from title screen. Under the direction of Dabney White Dixon. Electronic text (46 p. : ill. (some col.)) : digital, PDF file. Description based on contents viewed Aug. 1, 2007. Includes bibliographical references (p 45-46).
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Fontaine, Michael Christopher. "Allel-replacement mutagenesis of group A streptococci." Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285338.
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Parks, Thomas Edward. "Host genetic susceptibility to group A streptococcal disease." Thesis, University of Cambridge, 2016. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709471.
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Abe, Lucienne M. "Adhesion and internalization of group A streptococcus isolates found in Hawaii." Thesis, University of Hawaii at Manoa, 2003. http://proquest.umi.com/pqdweb?index=0&did=764803591&SrchMode=2&sid=1&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1233167604&clientId=23440.
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Vindebro, Reine. "Studies on secreted cysteine proteases of Streptococcus pyogenes : IdeS and SpeB." Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-88223.
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The pathogen Streptococcus pyogenes is a significant cause of human morbidity and mortality. Most of the work in this thesis is focused on streptococcal virulence factor IdeS, but the thesis also features work on SpeB, another streptococcal virulence factor. Both IdeS and SpeB are secreted cysteine proteases and both have previously been shown to degrade human IgG. IgG is the only known substrate for IdeS while SpeB is a more promiscuous protease with a larger number of identified substrates. A significant part of the data presented in this thesis is the result of designing and optimizing methods to detect and accurately measure the proteolytic degradation of IgG. Methods aimed at measuring the binding interactions between enzyme and substrate have also been frequently utilized. I show that IdeS is a monomeric protease, as opposed to previously published data that suggested it to be dimeric. IdeS cleaves the two heavy chains of IgG in a two-step reaction and I demonstrate that the first cleavage is magnitudes faster than the second one. This means that IdeS is a more efficient enzyme than previously thought. The difference in rate cannot completely be explained by a loss of affinity between IdeS and IgG after the cleavage of the first heavy chain. The velocity of IdeS is further increased by the presence of human Cystatin C, via an unknown mechanism. Cystatin C is normally a protease inhibitor and it having an opposite effect is puzzling.The synthesis and evaluation of novel inhibitors are also described. Peptide analogues mimicking the sequence surrounding the scissile bond on IgG - with an amino acid replaced with a more rigid motif - act as specific, but low-affinity, inhibitors of IdeS. The peptide analogues’ inhibitory capacity for SpeB and papain was also assayed.When it comes to SpeB, I show that it does not have IgG as a substrate under physiological conditions, in contrast to what was previously thought. This thesis does not only present findings on the IgG degrading capacity of IdeS and SpeB but also include data on fundamental enzymatic properties for these proteases.
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Almengor, Audry C. "Transcriptional regulation of the MGA virulence regulon in Streptococcus pyogenes." Access to abstract only; dissertation is embargoed until after 12/19/2006, 2005. http://www4.utsouthwestern.edu/library/ETD/etdDetails.cfm?etdID=115.
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Anderton, Stephen M. "A study of murine T lymphocyte responses to Streptococcus pyogenes." Thesis, University of Newcastle Upon Tyne, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287332.
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Turner, Claire Elizabeth. "SpyCEP : The Interleukin 8 Cleaving Streptococcus pyogenes Cell Envelope Proteinase." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501216.
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Abou, El Enien Ibrahim. "Caractérisation des propriétés biologiques du facteur d'opacité de Streptococcus pyogenes." Lyon 1, 1991. http://www.theses.fr/1991LYO1T067.
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Zarate, Bonilla Lina Johana. "Characterization of Chromosomally Encoded Toxin-Antitoxin Systems in Streptococcus pyogenes." Doctoral thesis, Humboldt-Universität zu Berlin, 2019. http://dx.doi.org/10.18452/20547.
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Streptococcus pyogenes ist ein humanpathogenes Bakterium, welches verschiedene Gewebe besiedeln kann und dadurch unterschiedliche Krankheiten verursacht. Die enorme Anpassungsfähigkeit des Bakteriums beruht auf dessen Fähigkeit, verschiedene, vom Wirt induzierte Stresskonditionen zu ertragen. Genetische Faktoren, die in diesem Zusammenhang eine Rolle spielen, sind Toxin-Antitoxin (TA) Systeme. Typ II TA Systeme kodieren für zwei Proteine, ein Toxin und ein Antitoxin, die einen stabilen TA Komplex bilden. Verschlechtern sich die Wachstumsbedingungen, kann das Antitoxin proteolytisch abgebaut werden, wodurch das freigesetzte Toxin essentielle zelluläre Prozesse des Bakteriums inhibiert. In dieser Studie charakterisierte ich zwei chromosomal kodierte ParDE TA Systeme des pathogenen Bakteriums S. pyogenes.
Ähnlich zu anderen Systemen werden das Toxin und das Antitoxin beider hier charakterisierten Systeme co-transkribiert und durch Stresseinwirkung (z.B. Aminosäure-mangel) induziert. Zudem konnten weitere posttranskriptionelle bzw. posttranslationale Mechanismen zur Regulierung der Genexpression beider Systeme nachgewiesen werden.
Die extrachromosomale Expression der Toxine ParE1 und ParE2 führten in S. pyogenes und Escherichia coli zum Zelltod, wobei die Co-expression der entsprechenden Antitoxine ParD1 und ParD2 die Toxizität minderte. Allerdings verursachte die Überexpression der Antitoxine allein ebenfalls eine Inhibierung des Zellwachstums. ParD1 hemmte die Zellteilung in E. coli, wobei der N-Terminus des Proteins entscheidend für diesen Effekt zu sein schien.
Zusammengefasst erweitern die Ergebnisse dieser Arbeit unser Verständnis von ParE Toxinen und verdeutlichen die diversen Mechanismen, welcher sich TA Systeme bedienen, um die bakterielle Physiologie zu beeinflussen. Zusätzlich gibt diese Arbeit einen Einblick in mögliche Mechanismen, die S. pyogenes implementiert, um Stresskonditionen im Wirt zu überdauern.Streptococcus pyogenes is a human pathogen with a remarkable ability to colonize different tissues and to endure diverse host-induced stress conditions through mechanisms that have yet to be fully understood. One strategy employed by bacteria to cope with changing environments are toxin-antitoxin (TA) genetic modules. Under non-ideal conditions, the antitoxin is subject to proteolysis and thus the freed toxin protein can target crucial pathways in the cell modulating bacterial growth. This study, describes the characterization of two chromosomally encoded ParDE-like TA systems from the human pathogen S. pyogenes. The antitoxin-toxin genes of the parDEF1 and parDE2 TA systems are co-transcribed and triggered by stress-induced conditions. The parDE2 TA showed an inspected mRNA processing under amino acid starvation which suggest a putative post-transcriptional regulation. At the post-translational level, both systems are controlled by ClpXP antitoxin-protein degradation in vivo, an important factor for TA triggering. Furthermore, bacterial plasmid-based expression of the toxins ParE1 and ParE2 resulted in effects in cell viability while the antitoxin molecules ParD1 and ParD2 were able to prevent the toxins lethality, respectably. Unlike canonical antitoxins, both ParD1 and ParD2 molecules also displayed deleterious effects, which seemed to be exclusive and related with the N-terminus domain potentially involved in DNA-interaction. Finally, the ParE toxins presented remarkable plasticity, able to harm not only gyrase but also topoisomerase IV, two important bacterial drug targets that modulate DNA-topology. These results expand the view on the ParE molecular targets and highlight the diverse mechanisms TAs employ to modulate bacterial physiology. We also provide more insights into possible mechanisms that S. pyogenes employs to endure stress in the host and efficiently cause disease.
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Tesorero, Melendez Rafael Angel. "Experimental validation for computationally predicted small RNAs of Streptococcus pyogenes." OpenSIUC, 2011. https://opensiuc.lib.siu.edu/theses/769.
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The human pathogen Streptococcus pyogenes (Group A Streptococcus or GAS) are a versatile Gram-positive cocci that havw shown complex modes of regulation of its different virulence factors. Discoveries of a few small non-coding RNAs (sRNAs) in S. pyogenes and their influence on the expression of virulence factors revealed an important role of sRNAs on S. pyogenes virulence. The genome-wide analysis of bacterial genomes for the discovery of sRNAs through computational methods has become an effective way to discover new sRNAs. In this study we provided a computational scheme where three different algorithms (RNAz, eQRNA, and sRNAPredict) were combined to increase the probabilities of predicting putative sRNAs within S. pyogenes' intergenic regions (IGR). A total of 46 candidates were chosen based on our criteria, and through Northern blot we analyzed each candidate. We obtained hybridization signals from twelve newly discovered sRNAs in S. pyogenes. Subsequently, we analyzed their sequence and their location within the IGR to find a putative -10 promoter region and possible Rho-independent terminator site, and their possible targets through computational methods. We further expanded our analysis of the new sRNAs by using Real-Time RT-PCR to determine the expression of sRNAs during different phases of growth. Our results showed that our computational scheme and experimental method was effective in predicting sRNAs previously undiscovered in S. pyogenes, and that more sRNAs are yet to be discovered and characterized, helping to further understand the regulation of virulence factors in S. pyogenes
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Swe, Pearl M., and n/a. "Mode of action of dysgalacticin and mechanism of its producer cell immunity." University of Otago. Department of Microbiology & Immunology, 2008. http://adt.otago.ac.nz./public/adt-NZDU20081119.111402.
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Dysgalacticin is a large, 21.5 kDa bacteriocin that belongs to subgroup B of the class III bacteriocins. It is ribosomally produced by Streptococcus dysgalactiae subsp. equisimilis strain W2580 and exerts inhibitory activity mainly against the medically important pathogen Streptococcus pyogenes by a "non-lytic" mechanism. Despite numerous studies of the mechanisms of action of a wide variety of bacteriocins and of the basis of their producer strain self-immunity, relatively little is known about the "non-lytic" class of bacteriocins. The structural gene encoding for dysgalacticin (dysA) was known to be carried on a small, rolling circle plasmid pW2580 (3.04 kb) (Heng et al., 2006). However, the dysgalacticin immunity gene (dysI) had not been identified prior to the present study. The aims of this research were to elucidate the mechanism of action of dysgalacticin against S. pyogenes and to identify the genetic basis and the mechanism of producer strain self-immunity. Recombinantly-produced dysgalacticin was used to determine the mode of action against S. pyogenes. Dysgalacticin was bactericidal for S. pyogenes, increasing the permeability of the cytoplasmic membrane and ultimately leading to leakage of intracellular potassium ions. Moreover, dysgalacticin dissipated the membrane potential and inhibited [�⁴C]serine uptake, a membrane potential-dependent process in S. pyogenes. Interestingly, dysgalacticin inhibited glucose fermentation by non-growing cell suspensions and blocked transport of both glucose and the nonmetabolisable analogue 2-deoxyglucose. This finding indicates that dysgalacticin may target the phosphophenolpyruvate (PEP)-dependent glucose and mannose phosphotransferase system (PTS) of S. pyogenes. Taken together, these data suggest that dysgalacticin targets the glucose-PTS and/or mannose-PTS as a receptor, leading to inhibition of sugar uptake, and a subsequent dissipation of the membrane potential leading to cell death.
Complementation studies demonstrated that dysI is located on pW2580. RNA analysis showed that dysI is co-transcribed with genes encoding for the plasmid copy control protein, copG and replication initiation protein, repB. S. pyogenes transformed with a plasmid containing dysI displayed a markedly higher dysgalacticin MIC (1024 nM) than the corresponding dysgalacticin-sensitive, plasmid-negative strain (8 nM). Further studies of this DysI-expressing S. pyogenes showed that membrane integrity, glucose fermentation and [�H]2DG uptake were not affected by dysgalacticin treatment. These findings are consistant with a mechanism whereby the immunity peptide binds to the target-binding site of dysgalacticin, effectively blocking access by the bacteriocin. H₆DysI was found to localise to the cytoplasmic membrane, further indicating that DysI may bind to the proposed target of dysgalacticin, i.e., the membrane-bound glucose-PTS and mannose-PTS. Thus both the mode of action and the producer strain self-immunity of dysgalacticin are likely to be cytoplasmic-membrane based.
Homology searching revealed that the bacteriocin SA-M7 produced by M-type 57 S. pyogenes has structural similarities to dysgalacticin, as do two hypothetical proteins, EF1097 and YpkK, of Enterococcus faecalis and Corynebacterium jeikeium, respectively (Heng et al., 2004, 2006). These proteins were all predicted to contain relatively unstructured N-termini and helix-loop-helix structured C-termini. In each case the C-termini contain two conserved cysteine residues that are predicted to form a disulphide bridge. Heterologous expression of SA-M57, EF1097 and YpkK in Escherchia coli demonstrated that all three proteins have antimicrobial activity, but of differeing activity spectra. Reductive-alkylation of SA-M57, EF1097 and YpkK confirmed that their predicted disulphide bonds were essential for biological activity. These proteins were later renamed streptococcin A-M57, enterococcin V583 and corynicin JK respectively. The outcome of preliminary domain-swapping experiments supported the existence of functional domain-type segments in streptococcin A-M57, enterococcin V583, corynicin JK and dysgalacticin. The N-terminal domain of each of these proteins and also the C-terminal domain of corynicin JK were successfully expressed in E. coli. The failure to express the C-termini of the remaining proteins was thought possibly due to toxicity of thses pepetides for the E. coli host. Nevertheless, the C-terminus of corynicin JK displayed an inhibitory spectrum apparently identical to that of the full-length corynicin, indicating that the N-terminus may not always be required for target binding of this class of antimicrobials. Preliminary mode of action studies revealed that streptococcin A-M57, enterococcin V583 and corynicin JK all resemble dysgalacticin in that they exert inhibitory activity by non-lytic means. These results, in combination with the protein structural predictions indicate that dysgalacticin, streptococcin A-M57, enterococcin V583 and corynicin JK are all members of the same basic class of "non-lytic" bactericoicns.
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Sylla, Maguette Dème. "Contribution à l'étude de l'action opsonisante des immunoglobulines sur les streptocoques du groupe A." Lyon 1, 1987. http://www.theses.fr/1987LYO1T126.
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Rivera, Martínez M. Alba. "Estudi epidemiològic d'infeccions invasives i no invasives produïdes per Streptococcus pyogenes." Doctoral thesis, Universitat Autònoma de Barcelona, 2008. http://hdl.handle.net/10803/3920.
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Streptococcus pyogenes és un patogen humà responsable d'un ampli ventall d'infeccions que varien des d'infeccions superficials com faringitis i impetigen a formes sistèmiques greus com fascitis necrosant (FN) i síndrome del xoc tòxic estreptocòccic (SSTS). El ressorgiment i persistència de formes invasives greus descrit des de mitjans dels anys 1980 ha motivat una intensa recerca sobre els aspectes epidemiològics, microbiològics i clínics d'aquestes infeccions. S'ha realitzat un estudi retrospectiu de base hospitalària que inclou 126 soques de S. pyogenes (27 procedents d'infeccions invasives i 99 d'infeccions no invasives) aïllades entre gener de 1999 i juny de 2003. Les soques de S. pyogenes es van caracteritzar en base a la distribució de tipus i subtipus emm i els perfils genètics de superantígens (SAgs) (speA-C, speF-J, speL, speM, ssa i smeZ). Tanmateix, es va determinar la prevalença i els mecanismes de resistència a macròlids, tetraciclina i levofloxacino.
Les formes clíniques més freqüents d'infecció invasiva van ser les infeccions de la pell i teixits tous (40,7%). La SSTS es va registrar en quatre (14,8%) dels casos invasius i es va associar a FN en la meitat dels casos. La majoria dels pacients afectats de quadres invasius eren adults, en particular d'edat avançada i de mitjana edat, i una elevada proporció presentaven factors predisposants, destacant l'alteració de la barrera cutània, la infecció per HIV, l'ús de drogues per via parenteral, i les neoplàsies.
En la col·lecció de 126 soques analitzada es van identificar un total de 29 tipus emm amb una distribució encapçalada pel tipus emm1 (17,5%), seguit d'emm3 (8,7%), emm4 (8,7%), emm12 (7,1%), emm28 (7,1%), emm11 (6,3%) i emm77 (6,3%). Aquests set tipus van constituir el 61,9% del total de soques. No es van observar diferències significatives en la distribució de tipus emm entre soques aïllades d'infeccions invasives i no invasives amb l'única excepció del tipus poc freqüent emm25 que es va trobar associat a infeccions invasives en addictes a drogues per via parenteral. Es va trobar una forta correlació entre el patró de SAgs i el tipus emm independentment del tipus d'infecció.
La resistència a eritromicina va mostrar un increment anual progressiu del 16,6% (1999) al 38,8% (2003) i va estar causada per soques pertanyents a 11 tipus emm. Les soques mef(A) positives dels tipus emm4, emm12 i emm75 i erm(B) positives dels tipus emm11 i emm25 constituïren el 80% de les soques resistents. La freqüència de resistència a tetraciclina va fluctuar durant el període estudiat (màxim 34,6% el 2002 i mínim 15,8% el 2001) i va ser superior en les soques resistents a eritromicina que en les soques sensibles (42,8% vs 18,7%). En les soques resistents a tetraciclina el gen tet(M) va ser el predominant i es va trobar en soques pertanyents a 14 tipus emm, mentre que el gen tet(O) només es va trobar en soques emm77. No es van observar diferències significatives en la prevalença de resistència a eritromicina ni a tetraciclina en el grup invasiu respecte del no invasiu.
La prevalença de resistència a levofloxacino fou del 3,2%, incloent quatre soques amb sensibilitat reduïda o resistència intermèdia (CIM 2-4 µg/ml) i dues soques amb resistència d'alt nivell (CIM >32 µg/ml). La resistència de baix nivell es va associar a substitucions únicament en ParC (Ser80Pro, Ser79Ala, Ser79Phe i Ala121Val), mentre que la resistència d'alt nivell es va relacionar amb mutacions en ParC (Ser79Phe i Ala121Val) i GyrA (Ser81Tyr).
Streptococcus pyogenes (GAS) is a human pathogen responsible for a wide array of infections, ranging from pharyngitis and impetigo to severe invasive infections such as necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). The resurgence and persistence of severe forms of GAS diseases reported since the mid 1980s have motivated intensive research on epidemiological, microbiological and clinical aspects of these diseases.
A retrospective hospital-based study was conducted including 126 GAS isolates (27 from invasive infections and 99 from non-invasive infections) collected from January 1999 to June 2003. GAS isolates were characterized by emm type and subtype and superantigen (SAg) gene profile (speA-C, speF-J, speL, speM, ssa and smeZ). The prevalence and mechanisms of macrolide, tetracycline and levofloxacin resistance were also determined.
The most common clinical presentations of invasive cases were skin and soft-tissue infections (40.7%). SSTS occurred in four cases (14.8%) and was associated to NF in half of the cases. Most invasive cases were found in adults, in particular among the elderly and the middle-aged, and a large proportion had underlying conditions, the most frequent being skin lesions, HIV infection, injection drug use, and malignancy.
A total of 29 emm types were identified among the 126 isolates; the most prevalent were emm1 (17.5 %), followed by emm3 (8.7 %), emm4 (8.7 %), emm12 (7.1 %), emm28 (7.1 %), emm11 (6.3 %) and emm77 (6.3 %). These seven emm types accounted for 61.9 % of isolates. There were no differences in the emm type distribution between invasive and non-invasive infections, except for emm25 isolates, which were associated with invasive infections in injecting drug users. The SAg gene profiles were closely associated with the emm type and were independent of the disease type.
The prevalence of erythromycin resistance showed an annual progressive increase from 16.6% (1999) to 38.8% (2003) and was caused by isolates belonging to 11 emm types. mef(A)-positive emm types 4, 12 and 75, and erm(B)-positive emm types 11 and 25 were responsible for up to 80% of the erythromycin-resistant isolates. The prevalence of tetracycline resistance fluctuated over the period studied (maximum 34.6% in 2002 and minimum 15.8% in 2001) and was higher in erythromycin-resistant isolates than in susceptible isolates (42.8% vs 18.7%). Among the tetracycline-resistant isolates, the tet(M) determinant was the most prevalent and was distributed in isolates belonging to 14 emm types, whereas tet(O) was only found in emm77 isolates. No significant differences in resistance rates to erythromycin or tetracycline were found between invasive and non-invasive isolates. The rate of resistance to levofloxacin was 3.2%, encompassing four isolates with reduced susceptibility or intermediate resistance (MIC 2-4 µg/ml) and two isolates with a high level of resistance (MIC >32 µg/ml). Low-level resistance was associated with alterations in ParC (Ser80Pro, Ser79Ala, Ser79Phe and Ala121Val), while high-level resistance was associated with alterations involving both ParC (Ser79Phe and Ala121Val) and GyrA (Ser81Tyr).
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Whatmore, Adrian Mark. "Sequence analysis of the emm-like gene family of Streptococcus pyogenes." Thesis, University of Newcastle Upon Tyne, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357642.
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Alam, Faraz Mainul. "Modelling nasopharyngeal colonisation by Streptococcus pyogenes : bioluminescence and other longitudinal techniques." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/14463.
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Streptococcus pyogenes causes an estimated 616 million pharyngitis cases per year and a variety of invasive diseases such as necrotising fasciitis and toxic shock syndrome. The human nasopharynx is the major reservoir for all S. pyogenes infection, including severe invasive disease. A combination of biophotonic imaging (BPI) and direct nasal sampling techniques were used to longitudinally measure the in vivo carriage of S. pyogenes, looking at the effects of virulence factor expression on carriage and transmission and to enable vaccine evaluation. Direct nasal sampling demonstrated that the two component regulatory system, CovR/S, is required for infection and transmission from the nasopharynx. The fitness cost conferred by covR/S mutation in the nasopharynx may explain why S. pyogenes with altered covR/S have not become prevalent in community infections despite conferring a selective advantage in invasive infection. Bioluminescent S. pyogenes strains expressing the luxABCDE operon demonstrated a growth deficit independent of the target site for integration in vitro that manifested as a fitness cost during infection in vivo. Notwithstanding this, bioluminescence expression permitted longitudinal quantitation of S. pyogenes within the nasopharynx using BPI. Intramuscular vaccination with heat killed streptococci or the streptococcal chemokine protease SpyCEP conferred protection against pharyngeal infection in this model. These longitudinal techniques allow for S. pyogenes to be tracked in the nasopharynx non-invasively, and allow for new insights into the pathogenesis of this disease.
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Power, Daniel Aaron, and n/a. "Non-culture based studies of the human upper respiratory tract microbiota and preliminary considerations of the influence of bacteriocin producing commensal and pathogenic oral streptococci." University of Otago. Department of Microbiology & Immunology, 2007. http://adt.otago.ac.nz./public/adt-NZDU20070620.160726.
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The upper respiratory tract (URT) of humans is complex and interconnected region and comprises several major ecosystems including the oral cavity, oropharynx, nasal cavity, sinuses, nasopharynx and middle ear. Most of the anatomical locations within the URT are colonised with a normal bacterial microbiota, within which are often organisms having the potential to cause disease. The diseases of the URT are both varied and frequent in their occurrence, and conditions such as otitis media, rhinosinusitis and pharyngitis are sources of morbidity and mortality in adults and children in both developing and developed countries.
The study of diseases of the URT has traditionally been based on application of culture-based methods in which the infection-implicated organisms are first grown in vitro and then studied further. Ongoing advances in DNA-based techniques have led to the development of new molecular tools for the study of infectious diseases. One such technique is PCR-denaturing gradient gel electrophoresis (PCR-DGGE). This is a PCR-based tool that allows the investigation of microbial communities independent of culture. Although this technique has been applied extensively in the study of the gastrointestinal tract, the vagina and endodontic infections in humans, there have been few reports of its application to URT infections. PCR-DGGE was applied in the present study to investigate (a) the bacteria present in the middle ear of children suffering from otitis media with effusion (OME), (b) the microbiota associated with the sinuses in patients with chronic rhinosinusitis (CRS) and (c) perioperative changes in the bacterial population of the middle meatus of patients undergoing nasal or sinus surgery. The analysis of the middle ear fluid samples indicated an increased role in OME for the newly-discovered pathogen Alloiococcus otitidis and also the possible involvement of certain coryneform bacteria and coagulase-negative staphylococci in the aetiology of this condition. PCR-DGGE analysis of patients with CRS revealed a polymicrobial disease with considerable variability in the predominant species detected when multiple, serial samples were evaluated. The perioperative audit showed that when good clinical practice is adhered to, there was no apparent introduction of potentially-harmful organisms into the middle meatus.
Streptococcus salivarius is a common, commensal inhabitant of the oral cavity of humans and has also been shown to inhabit the nasopharynx of infants. S. salivarius is also a well known producer of bacteriocins with activity directed against Streptococcus pyogenes. One such strain, S. salivarius K12, is now marketed in New Zealand as the probiotic, K12 Throat Guard[TM]. In the present study, S. salivarius K12 was compared with two additional strongly-inhibitory S. salivarius (strains T18A and T30A) for activity against the common causative pathogens of otitis media. A paediatric formulation of strain K12 was also tested in a pilot clinical trial for its ability to colonise the URT of young children. Although the levels of colonisation of these subjects was not as high as typically obtained with use of the K12 Throat Guard[TM] formulation, it was considered that further development of the paediatric formulation is warranted, particularly with respect to use of a different pre-treatment regimen. In other studies, the molecular basis for the unusual in vitro inhibitory activity of S. salivarius strain T30A was investigated. Although this still remains unresolved, other observations made during the course of this study have led to the introduction of a schema for the division of inhibitory S. salivarius into three groups based on (a) their sensitivity to the lantibiotic salivaricin A and (b) the structure of their salivaricin A genetic locus. This grouping is analogous to the "rock-paper-scissors" system previously described for colicin-producing strains of E. coli.
Streptococcus pneumoniae is a major human pathogen responsible for a variety of diseases in humans. There have been very few reports of bacteriocin production by S. pneumoniae when compared to other streptococcal species. In the present study a putative cluster of bacteriocins encoded by the blp locus has been investigated. The distribution of the individual blp determinants within this locus was evaluated in a collection of S. pneumoniae strains using PCR. The blp genes were detected in 92% of 57 tested strains and a variant form (termed the B-form) of the cluster was identified that appeared to have arisen due to a genetic recombination event. In this case an approximately 250 bp portion of the blpMNO cluster appears to have recombined into blpK of the blpIJK cluster. Attempts were made to express the putative bacteriocin peptide genes in an Escherichia coli expression system. Failure to achieve expression was taken to indicate that these bacteriocin-like peptides may be toxic for the host producer cells under these test conditions. Future attempts to achieve expression of the Blp peptides, could explore the use of different fusion proteins, a Gram-positive expression host or a cell-free protein expression system.
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Amicis, Karine Marafigo De. "Análise in vitro da capacidade de cobertura da vacina em desenvolvimento contra Streptococcus pyogenes." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-02082013-144608/.
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O Streptococcus pyogenes (Grupo A de Lancefield) é uma bactéria Gram positiva e beta-hemolítica, responsável por infecções, tais como Faringite, Sepse, Fasciíte Necrotizante e Síndrome do Choque Tóxico Estreptocócico. Indivíduos suscetíveis podem desenvolver sequela não supurativa auto-imune pós-estreptocócica, como a Febre Reumática, Doença Reumática Cardíaca e a Glomerulonefrite Aguda. A proteína M é o principal antígeno bacteriano. Consiste em aproximadamente 450 resíduos de aminoácidos dispostos em quatro regiões (A, B, C e D), contendo alguns blocos de repetições. As regiões C e D são conservadas e a N-terminal (regiões A e B) é polimórfica. Atualmente, existem mais de 250 genótipos de emm conhecidos em todo o mundo, de acordo com o Centers for Disease Control and Prevention. Há vários anos, o desenvolvimento de uma vacina contra S. pyogenes (StreptInCor - identificação médica) foi iniciado, com base na região conservada da proteína M, com o objetivo de proteger o indivíduo vacinado contra infecções estreptocócicas, sem causar reações autoimunes. No presente estudo foi analisada a capacidade \"in vitro\" de anticorpos anti-StreptInCor neutralizarem/opsonizarem as cepas de S. pyogenes mais freqüentes em São Paulo, através da análise do reconhecimento das cepas por soros de camundongos imunizados com StreptInCor. Também foi avaliada por Western blotting a presença de anticorpos de reação cruzada dirigidos ao tecido cardíaco valvular humano. Anticorpos anti-StreptInCor foram capazes de neutralizar/opsonizar, pelo menos, cinco diferentes cepas mostrando que a imunização com StreptInCor pode ser eficaz contra várias cepas de S. pyogenes, assim como prevenir a infecção e sequelas subsequentes, sem causar reações auto-imunes.Streptococcus pyogenes (Group A) is a Gram positive and beta-hemolytic bacteria, responsible for infections such as Pharyngitis, Sepsis, Necrotizing Fasciitis and Streptococcal Toxic Shock Syndrome. Susceptible individuals may develop post-streptococcal non-suppurative autoimmune sequelae such as Rheumatic Fever, Rheumatic Heart Disease and Acute Glomerulonephritis. The M protein is the major bacterial antigen. It consists of approximately 450 amino acid residues arranged in four regions (A, B, C and D), containing some repeated blocks. C and D regions are conserved and the N-terminus (regions A and B) is polymorphic. Currently there are over 250 known emm genotypes worldwide, according to the Centers for Disease Control and Prevention. Several years ago the development of a vaccine against S. pyogenes (StreptInCor - medical identification) was initiated, based on the M protein conserved region, aiming to protect against streptococcal infections without causing autoimmune reactions. In the present study we analyzed the \"in vitro\" ability of anti-StreptInCor antibodies to neutralize/opsonize the most frequent S. pyogenes strains in Sao Paulo by examining the strains recognition by sera from StreptInCor immunized mice. We also evaluated the presence of cross reactive antibodies directed to the human heart valve tissue by Western blotting. Anti-StreptInCor antibodies were able to neutralize/opsonize at least 5 strains, showing that the immunization with StreptInCor can be effective against several S. pyogenes strains as well as preventing infection and subsequent sequelae, without causing autoimmune reactions.
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Noschang, Juliana. "Variabilidade genética de isolados de Streptococcus pyogenes por meio de marcadores RAPD." reponame:Repositório Institucional da UFPR, 2013. http://hdl.handle.net/1884/29830.
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Os estreptococos B-hemoliticos do grupo A (Streptococcus pyogenes) causam varias doencas humanas e estao associados com febre reumatica e glomerulonefrite pos-estreptococica. A sorotipagem dos antigenos M e T tem sido a maneira mais comum de tipagem destes patogenos, entretanto, para alguns isolados a tipagem por este metodo nao e satisfatoria, pois cerca de 15 a 40% dos isolados nao sao tipaveis. Alem disso, estes metodos de sorotipagem nao sao eficientes para diferenciacao clonal em estudos epidemiologicos. Marcadores moleculares sao ferramentas importantes capazes de diferenciar sorotipos de estreptococos do grupo A, provendo informacoes na elucidacao de surtos epidemiologicos e diagnostico. Marcadores RAPD foram utilizados para detectar polimorfismos em isolados de S. pyogenes de um surto de faringotonsilite estreptococica ocorrido em uma industria alimenticia, em marco de 2004 na cidade de Curitiba - PR. Foram utilizados 26 isolados do surto, 11 isolados desta especie, nao relacionados com o surto, duas linhagens referencias de sorotipo nefritogenico e uma de sorotipo reumatogenico. Foi observada variabilidade genetica entre os isolados de S. pyogenes do surto. A analise de gcluster h utilizando-se o coeficiente de Jaccard, mostrou dois grupos de isolados sem relacao clonal entre si, sugerindo a circulacao de dois sorotipos na industria alimenticia. Os resultados sugerem que o surto foi causado por sorotipo nefritogenico, com possibilidade de ter sido o sorotipo M4. A utilizacao de mais linhagens referencias nefritogenicas e reumatogenicas e a sorotipagem da proteina M possibilitariam a identificacao dos sorotipos causadores do surto de glomerulonefrite estreptococica na industria alimenticia, em Curitiba-PR, naquela ocasiao.