Functional Characterization Of The Outer Membrane Protein Tolc Of Salmonella Enterica Subspecies Enterica Serovar Typhi And Its Association With Virulence

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dc.contributor.authorHussain, Ashraf
dc.date.accessioned2019-01-31T02:21:20Z
dc.date.available2019-01-31T02:21:20Z
dc.date.issued2018-02
dc.description.abstractAlthough Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) has been well studied, only a few of its outer membrane proteins (OMPs) have been functionally characterized. In this study, a tolC deletion mutant was generated to study the biological functions of TolC in S. Typhi strain that was isolated from an acute typhoid patient. Deletion of TolC caused increase susceptibility to a range of antimicrobials challenge, compromised membrane integrity, and reduced efflux activity of S. Typhi. In addition, the ΔtolC mutant was shown to have lower adhesion and invasion capability in an in vitro human cell culture infection model. Further confirmation of this attenuation was investigated by the reverse transcription (RT)-PCR analysis which showed reduced transcription of bacterial genes related to the invasion of the Salmonella. Consequently, when invasion tests were performed with the tolC mutant, the tolC mutant was significantly less able to invade HT-29 and THP-1 cells than its parental strain. Furthermore, the in vitro analysis revealed that the intracellular presence of the tolC mutant was hyper cytotoxic to human macrophages as compared to the wild-type strain, and it elicited the increased transcription of proinflammatory chemokine genes in human macrophages. Collectively, these data suggest that TolC function is required for S. Typhi to inhibit host cell death and dampen host immune responses. Deletion of the tolC conferred a distinct phenotype from the wild-type parent strain. This indicates that the function of TolC is distinct from its protein partners in both effluxes of substrates and in virulence. This study suggests the possible functions of TolC in the virulence and pathogenicity of S. Typhi.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/7700
dc.language.isoenen_US
dc.publisherUniversiti Sains Malaysiaen_US
dc.subjectThe outer membrane protein tolc of Salmonella entericaen_US
dc.subjectits association with virulenceen_US
dc.titleFunctional Characterization Of The Outer Membrane Protein Tolc Of Salmonella Enterica Subspecies Enterica Serovar Typhi And Its Association With Virulenceen_US
dc.typeThesisen_US
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