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dc.contributor.advisorChakravortty, Dipshikha
dc.contributor.authorGarai, Preeti
dc.date.accessioned2018-10-10T12:16:19Z
dc.date.available2018-10-10T12:16:19Z
dc.date.submitted2015
dc.identifier.urihttps://etd.iisc.ac.in/handle/2005/4090
dc.description.abstractCarbon starvation genes mediate the cross-talk between metabolism and pathogenesis of Salmonella Typhimurium Salmonella enterica serovar Typhimurium (S. Typhimurium) can infect a wide range of host animals to cause diseases like gastroenteritis and typhoid fever. Therefore it serves as an ideal model organism to study Salmonella pathogenesis. The adaptability of Salmonella to diverse environmental conditions is due to its ability to utilize a plethora of nutrients. While various carbon and nitrogen sources are supplied by the host, the role of peptides as alternate nutrient source for Salmonella is not clearly defined. These peptides are presented by the host as antimicrobial peptides, but can serve as nutrients too, once taken up by peptide transporters and digested by the pathogen. The importance of peptide transporters is also reported for alternate functions such as quorum sensing, competence, chemotaxis and virulence. The ABC transporters of peptides are well studied in Salmonella, whereas little is known about the putative peptide transporter family named as carbon starvation genes which lack ATP binding site. Two carbon starvation (cst) genes, cstA and yjiY, are the only genes known to belong to this group of peptide transporters in Salmonella. cstA was previously reported to be required for virulence of Salmonella in C. elegans. To establish the role of cst genes in the metabolism and pathogenesis of S. Typhimurium, the knockout strains for the genes cstA and yjiY in S. Typhimurium, denoted as ΔcstA and ΔyjiY, were generated. The metabolic capacity of these mutants was checked by phenotype microarray revealing that cst knockout strains were compromised in peptide metabolism and ΔyjiY strain showed remarkable difference from the wild type in the ability to utilize a few peptides. Fluorescent peptide uptake assay showed reduced uptake of specific dipeptides by ΔyjiY strain. Thus, cst genes contribute to metabolism of Salmonella by transporting specific peptides. Upon infecting C. elegans, ΔcstA was unable to colonize the intestine of the worm verifying the reported role of cstA. However, in mammalian model systems, ΔyjiY, but not ΔcstA, was unable to invade various types of host cells, attributed to defective adhesion of ΔyjiY because of lack of flagella. The in vivo significance of yjiY was established when ΔyjiY showed decreased colonization of mouse gut. Transcriptome analysis showed upregulation of the virulence factor mgtC in ΔyjiY, which led to better proliferation of ΔyjiY inside macrophages. The expression of mgtC is induced in the absence of proline suggesting that yjiY might be involved in transporting proline rich peptides. Therefore, both cst genes are required for the virulence of Salmonella, but in different host systems. When biofilm forming ability of the wild type and cst mutant strains was tested in vitro, only ΔyjiY strain was unable to form biofilm. Confocal microscopy and assessment of rdar morphotype revealed that ΔyjiY strain lacked extracellular polymeric substance (EPS) production, which is an essential component of biofilm matrix. The mechanism behind was found to be the downregulation in the expression of the biofilm master regulator gene, csgD that controls EPS biosynthesis in Salmonella. Conclusively, yjiY is required for EPS biosynthesis and hence biofilm formation in Salmonella.en_US
dc.language.isoen_USen_US
dc.relation.ispartofseriesG27311;
dc.rightsI grant Indian Institute of Science the right to archive and to make available my thesis or dissertation in whole or in part in all forms of media, now hereafter known. I retain all proprietary rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertationen_US
dc.subjectSalmonellaen_US
dc.subjectSalmonella typhimuriumen_US
dc.subjectcst Genesen_US
dc.subjectBiofilm Formationen_US
dc.subjectSalmonella Pathogenicity Island 2en_US
dc.subjectCarbon Starvation Gene yjiYen_US
dc.subject.classificationMicrobiology and Cell Biologyen_US
dc.titleCarbon Starvation Genes Mediate the Cross-talk Between Metabolism and Pathogenesis of Salmonella Typhimuriumen_US
dc.typeThesisen_US
dc.degree.namePhDen_US
dc.degree.levelDoctoralen_US
dc.degree.grantorIndian Institute of Scienceen_US
dc.degree.disciplineFaculty of Scienceen_US


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