Single missense mutations in Vi capsule synthesis genes confer hypervirulence toSalmonellaTyphi

Abstract

AbstractMany bacterial pathogens, including the human exclusive pathogenSalmonellaTyphi, express capsular polysaccharides as a crucial virulence factor. Here, throughS.Typhi whole genome sequence analyses and functional studies, we found a list of single point mutations that makeS. Typhi hypervirulent. We discovered a single point mutation in the Vi biosynthesis enzymes that control the length or acetylation of Vi is enough to create different capsule variants ofS.Typhi. All variant strains are pathogenic, but the hyper-capsule variants are particularly hypervirulent, as demonstrated by the high morbidity and mortality rates observed in infected mice. The hypo-capsule variants have primarily been identified in Africa, whereas the hyper-capsule variants are distributed worldwide. Collectively, these studies increase awareness about the existence of different capsule variants ofS.Typhi, establish a solid foundation for numerous future studies onS.Typhi capsule variants, and offer valuable insights into strategies to combat capsulated bacteria.