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ROLE OF THE PHOSPHOENOLPYRUVATE: CARBOHYDRATE PHOSPHOTRANSFERASE SYSTEM IN THE VIRULENCE OF THE GROUP A STREPTOCOCCUS

dc.contributor.advisorMcIver, Kevin Sen_US
dc.contributor.authorGera, Kanikaen_US
dc.date.accessioned2014-06-24T06:05:32Z
dc.date.available2014-06-24T06:05:32Z
dc.date.issued2014en_US
dc.identifier.urihttp://hdl.handle.net/1903/15301
dc.description.abstractGroup A Streptococcus (GAS) is a fastidious microorganism that has adapted to a variety of niches in the human body by sensing its surroundings and modifying its metabolism to elicit a wide array of diseases. The Phosphoenolpyruvate Phosphotransferase System (PTS) is a primary mechanism by which many bacteria transport sugars and sense the carbon state of the cell. The PTS uses the non-sugar specific `general' proteins EI and Hpr, and sugar-specific membrane-spanning proteins (EIIs) for the PTS-mediated uptake of each sugar. The role of PTS in carbohydrate metabolism in GAS was investigated by generating a &Delta;ptsI mutant (EI deficient) in three different strains belonging to M1T1 and one of M4 GAS. All &Delta;<italic>ptsI</italic> mutant strains tested were unable to grow on multiple carbon sources (PTS and non-PTS). Complementation with <italic>ptsI</italic> expressed under its native promoter in single copy was able to rescue the growth defect of the mutant. Additional studies analyzing the role of PTS in pathogenesis of GAS, showed a `hypervirulent' phenotype in the absence of &Delta;<italic>ptsI</italic> from M1T1 using soft tissue model of infection. The appearance of significantly larger and more severe ulcerative lesion observed in mice infected by &Delta;<italic>ptsI</italic> was correlated with increased transcript levels of <italic>sagA</italic> and early Streptolysin S (SLS) activity during exponential phase growth. The role of SLS in increased pathogenesis of &Delta;<italic>ptsI</italic> was investigated by the creation of a double mutant strain (&Delta;<italic>ptsI sagB</italic>) that lacks the ability to secrete SLS. The infection of mice with a &Delta;<italic>ptsI sagB</italic> double mutant resulted in a lesion comparable to either a wild type or a <italic>sagB</italic> mutant alone. In addition to SLS, it was found that PTS influences the secretion of cysteine protease SpeB and the ability of GAS to produce capsule. This regulatory effect was found to be dependent on the status of sensor kinase (CovS) of the CovR/S two-component system. Moreover, PTS was shown to phosphorylate PTS regulatory domains (PRD) of a global virulence regulator, Mga, resulting in alteration of its regulon in both M1T1 and M4 background, suggesting the ability of GAS to alter expression of Mga regulon in response to carbohydrate availability. Overall, our studies indicate that a functional PTS is important for utilizing PTS and non-PTS sugars and influences virulence during GAS infection.en_US
dc.language.isoenen_US
dc.titleROLE OF THE PHOSPHOENOLPYRUVATE: CARBOHYDRATE PHOSPHOTRANSFERASE SYSTEM IN THE VIRULENCE OF THE GROUP A STREPTOCOCCUSen_US
dc.typeDissertationen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentCell Biology & Molecular Geneticsen_US
dc.subject.pqcontrolledMolecular biologyen_US
dc.subject.pqcontrolledMicrobiologyen_US


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