Capsule-independent bacteriophages reveal unexpected diversity of Salmonella Typhi phage ecology
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Bacteriophages that infect Salmonella enterica serovar Typhi ( S. Typhi), the cause of typhoid fever, are regarded as specialized, because all previously characterized phages depend on the Vi capsular polysaccharide for infection. Whether capsule-independent infection strategies exist has remained unclear. Here we identify environmental phages that infect S. Typhi both in the presence and absence of Vi. Screening 140 urban wastewater samples from Dhaka, Bangladesh, where typhoid is endemic, we recovered phages infecting a Vi-deficient S. Typhi strain from 41 samples (29%). All 41 phages also infected the isogenic Vi-expressing host, although 28 did so with 10- to 10⁵-fold lower infection efficiency, and suppressing capsule expression increased susceptibility to 23, indicating an inhibitory effect of Vi on infection by many these phages. All 41 phages infected S. Paratyphi A and nine infected a monophasic S. Typhimurium, a broader host range than the Vi-dependent phages, which were restricted to Vi-expressing Typhi. Across 26 circulating genotypes, capsule suppression increased susceptible genotypes per phage by 1.51 on average (Wilcoxon p = 5.76 × 10⁻⁶), though four genotypes remained resistant to all phages tested, indicating additional determinants of susceptibility. Whole-genome sequencing of 27 phages identified three genera in two families, predominantly Teetrevirus (19/27); TerL phylogeny separated these from classical Vi-dependent phage lineages. Together, these findings reveal a broader-host-range component of Typhi phage ecology and show that Vi dependence is not a universal feature of phages capable of infecting S. Typhi.
Importance
The Vi capsule is a defining surface antigen of Salmonella Typhi and is required for infection by characterized Typhi phages. Here, we show that this dependence is not universal. In a typhoid-endemic setting, we identified environmental phages capable of infecting S. Typhi in the absence of Vi, revealing a previously underrecognized infection strategy. These Vi-independent phages showed broader host ranges than classical Vi-dependent phages, with susceptibility varying across S. Typhi lineages. Genomic characterization identified that these phages were from lineages distinct from Vi-dependent phages. Together, these findings reveal greater diversity in S. Typhi-phage interactions than previously appreciated and suggest that Vi-dependent specialists represent only one component of a broader Typhi-phage ecological landscape. As these phages were identified before the national introduction of the Vi-typhoid conjugate vaccine, they also provide a baseline for future studies examining whether population-level targeting of the Vi capsule is accompanied by changes in Typhi-phage ecology.
