title: lac repressor is an antivirulence factor of Salmonella enterica: its role in the evolution of virulence in Salmonella.
abstract: The genus Salmonella includes many pathogens of great medical and veterinary importance. Bacteria belonging to this genus are very closely related to those belonging to the genus Escherichia. lacZYA operon and lacI are present in Escherichia coli, but not in Salmonella enterica. It has been proposed that Salmonella has lost lacZYA operon and lacI during evolution. In this study, we have investigated the physiological and evolutionary significance of the absence of lacI in Salmonella enterica. Using murine model of typhoid fever, we show that the expression of LacI causes a remarkable reduction in the virulence of Salmonella enterica. LacI also suppresses the ability of Salmonella enterica to proliferate inside murine macrophages. Microarray analysis revealed that LacI interferes with the expression of virulence genes of Salmonella pathogenicity island 2. This effect was confirmed by RT-PCR and Western blot analysis. Interestingly, we found that SBG0326 of Salmonella bongori is homologous to lacI of Escherichia coli. Salmonella bongori is the only other species of the genus Salmonella and it lacks the virulence genes of Salmonella pathogenicity island 2. Overall, our results demonstrate that LacI is an antivirulence factor of Salmonella enterica and suggest that absence of lacI has facilitated the acquisition of virulence genes of Salmonella pathogenicity island 2 in Salmonella enterica making it a successful systemic pathogen.
authors.affiliation: Centre for Infectious Disease Research and Biosafety Laboratories, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, India.
authors.forename: Sandeepa M
authors.initials: SM
authors.lastname: Eswarappa
authors.forename: Guruswamy
authors.initials: G
authors.lastname: Karnam
authors.forename: Arvindhan G
authors.initials: AG
authors.lastname: Nagarajan
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Dipshikha
authors.initials: D
authors.lastname: Chakravortty
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D044404:Genomic Islands; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000378:metabolism*; D019779:Salmonella enterica / Q000235:genetics* / Q000472:pathogenicity*; D017386:Sequence Homology, Amino Acid; D014435:Typhoid Fever / Q000382:microbiology*; D014774:Virulence
chemical_list: D012097:Repressor Proteins