Shigella serotypes associated with carriage in humans establish persistent infection in zebrafish

Abstract

Shigella represents a paraphyletic group of human-adapted Escherichia coli lineages that converged towards the same enteropathogenic pathovar. In low-income countries, Shigella is typically transmitted by ingestion of contaminated water and food, while in high-income countries sexual transmission among men who have sex with men (MSM) is the dominant route of transmission. Although more than 40 different serotypes of Shigella have been reported globally, within the MSM community the majority of reported cases are attributed to three Shigella serotypes: the Shigella sonnei unique serotype (Ss) and the Shigella flexneri serotypes 2a and 3a. Here, using a zebrafish infection model, we demonstrate that Shigella can establish persistent infection in vivo. In this case, bacteria are not cleared by the host immune system and become tolerant to therapeutic doses of antibiotics. We show that persistence is dependent on the Shigella O-Antigen, a key constituent of the bacterial cell surface and determinant of serotype classification. Representative isolates of three Shigella serotypes associated with global dissemination and MSM transmission (S. sonnei Ss, S. flexneri 2a and 3a) all persist in zebrafish, while a serotype not associated with MSM transmission (S. flexneri 5a) does not. Strikingly, Shigella serotypes which establish persistent infection fail to promote macrophage cell death in vivo. We conclude that zebrafish can be a valuable platform to illuminate host and pathogen factors underlying the establishment of persistent infection with Shigella in humans. HighlightsO_LIShigella can establish persistent infection in zebrafish C_LIO_LIEstablishment of persistent infection in vivo depends on Shigella serotype C_LIO_LIThe same serotypes establishing persistent infection in zebrafish are prevalent in a patient group in whom persistent infection is observed C_LIO_LIShigella serotypes which establish persistent infection fail to promote macrophage cell death in vivo C_LI In BriefIn high-income countries, sexual transmission among men who have sex with men (MSM) is the dominant cause of domestic Shigella transmission. Torraca et al. discover that three serotypes of Shigella associated with MSM transmission also persist in zebrafish. These results indicate that Shigella serotypes associated with MSM transmission can establish carriage in the host, and highlight the use of zebrafish infection to study Shigella persistent infection in humans.