title: Loss of very-long O-antigen chains optimizes capsule-mediated immune evasion by Salmonella enterica serovar Typhi.
abstract: Expression of capsular polysaccharides is a variable trait often associated with more-virulent forms of a bacterial species. For example, typhoid fever is caused by the capsulated Salmonella enterica serovar Typhi, while nontyphoidal Salmonella serovars associated with gastroenteritis are noncapsulated. Here we show that optimization of the immune evasive properties conferred by the virulence-associated (Vi) capsular polysaccharide involved an additional alteration to the cell envelope of S. Typhi, namely inactivation of the fepE gene, encoding the regulator of very-long O-antigen chains. Introduction of the capsule-encoding viaB locus into the nontyphoidal S. enterica serovar Typhimurium reduced complement deposition in vitro and intestinal inflammation in a mouse colitis model. However, both phenotypes were markedly enhanced when the viaB locus was introduced into an S. Typhimurium fepE mutant, which lacks very-long O-antigen chains. Collectively, these data suggest that during the evolution of the S. Typhi lineage, loss of very-long O-antigen chains by pseudogene formation was an adaptation to maximize the anti-inflammatory properties of the Vi capsular polysaccharide.
  
  
  OBJECTIVE
  Genomic comparison illustrates that acquisition of virulence factors by horizontal gene transfer is an important contributor to the evolution of enteric pathogens. Acquisition of complex virulence traits commonly involves horizontal transfer of a large gene cluster, and integration of the gene cluster into the host genome results in the formation of a pathogenicity island. Acquisition of the virulence-associated (Vi) capsular polysaccharide encoded by SPI7 (Salmonella pathogenicity island 7) was accompanied in the human-adapted Salmonella enterica serovar Typhi by inactivation of the fepE gene, encoding the regulator of very-long O-antigen chains. We show that the resulting loss of very-long O-antigen chains was an important mechanism for maximizing immune evasion mediated by the Vi capsular polysaccharide. These data suggest that successful incorporation of a capsular polysaccharide requires changes in the cell envelope of the hosting pathogen.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Crawford
authors.forename: Tamding
authors.initials: T
authors.lastname: Wangdi
authors.forename: Alanna M
authors.initials: AM
authors.lastname: Spees
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Xavier
authors.forename: Renée M
authors.initials: RM
authors.lastname: Tsolis
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D000818:Animals; D003092:Colitis / Q000382:microbiology / Q000473:pathology; D003165:Complement System Proteins / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D057131:Immune Evasion; D051379:Mice; D008810:Mice, Inbred C57BL; D019081:O Antigens / Q000235:genetics / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000472:pathogenicity; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D014435:Typhoid Fever / Q000382:microbiology / Q000473:pathology*; D014774:Virulence
chemical_list: D019081:O Antigens; D011135:Polysaccharides, Bacterial; C054154:capsular polysaccharide, Salmonella; D003165:Complement System Proteins