Single missense mutations in Vi capsule synthesis genes confer hypervirulence toSalmonellaTyphi

Abstract

Many 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.

Antimicrobial properties of tomato juice and peptides against typhoidal Salmonella

“…To assess the efficacy of tdAMP-1 and tdAMP-2 against hyper-capsular bacteria, we have selected hyper-capsular/hypervirulent S . Typhi strains that are currently prevalent in endemic regions ( 34 ). Both tdAMP-1 and tdAMP-2 demonstrated efficacy against acapsular ( Fig.…”

“…Intriguingly, we have observed similar adaptations in S . Typhi ( 34 ). These findings suggest a parallel evolution of capsulated pathogens.…”

“…For the purpose of this investigation, we have chosen hyper-capsular/hypervirulent strains of S . Typhi that are currently prevalent in endemic regions ( 34 ). We found that both tdAMP-1 and tdAMP-2 demonstrated antimicrobial properties against acapsular and hyper-capsular/hypervirulent S. Typhi strains ( Fig.…”