title: Synergistic effect of mutations in invA and lpfC on the ability of Salmonella typhimurium to cause murine typhoid.
abstract: Penetration of the intestinal mucosa at areas of Peyer's patches is an important first step for Salmonella typhimurium to produce lethal systemic disease in mice. However, mutations in genes that are important for intestinal invasion result in only moderately decreased virulence of S. typhimurium for mice. Here we report that combining mutations in invA and lpfC, two genes necessary for entry into Peyer's patches, results in a much stronger attenuation of S. typhimurium than inactivation of either of these genes alone. An S. typhimurium invA lpfC mutant was 150-fold attenuated by the oral route of infection but was fully virulent when the intestine was bypassed by intraperitoneal challenge of mice. During mixed-infection experiments, the S. typhimurium invA lpfC mutant showed a strong defect in colonizing Peyer's patches and mesenteric lymph nodes. These data suggest that mutations in invA and lpfC deactivate distinct pathways for intestinal penetration and colonization of Peyer's patches. While the inv-mediated pathway is widely distributed, the lpf operon is absent from many phylogenetic groups within the genus Salmonella. To investigate how acquisition of the lpf-mediated pathway for mucosal penetration contributed to evolution of virulence, we studied the relationship between the presence of the lpf operon and the pathogenicity for mice of 18 isolates representing 14 Salmonella serotypes. Only strains possessing the lpf operon were able to cause lethal infection in mice. These data show that both the invA- and lpfC-mediated pathways of intestinal perforation are conserved in mouse virulent Salmonella serotypes.
authors.affiliation: Department of Medical Microbiology and Immunology, Texas A&M University, College Station 77843-1114, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Bäumler
authors.forename: R M
authors.initials: RM
authors.lastname: Tsolis
authors.forename: P J
authors.initials: PJ
authors.lastname: Valentine
authors.forename: T A
authors.initials: TA
authors.lastname: Ficht
authors.forename: F
authors.initials: F
authors.lastname: Heffron
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D005260:Female; D005798:Genes, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D014435:Typhoid Fever / Q000209:etiology*; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; C075518:invA protein, Bacteria