Shigellaserotypes associated with carriage in humans establish persistent infection in zebrafish

Abstract

SummaryShigellarepresents a paraphyletic group of human-adaptedEscherichia colilineages that converged towards the same enteropathogenic pathovar. In low-income countries,Shigellais 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 ofShigellahave been reported globally, within the MSM community the majority of reported cases are attributed to threeShigellaserotypes: theShigella sonneiunique serotype (Ss) and theShigella flexneriserotypes 2a and 3a. Here, using a zebrafish infection model, we demonstrate thatShigellacan establish persistent infectionin 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 theShigellaO-Antigen, a key constituent of the bacterial cell surface and determinant of serotype classification. Representative isolates of threeShigellaserotypes associated with global dissemination and MSM transmission (S. sonneiSs,S. flexneri2a and 3a) all persist in zebrafish, while a serotype not associated with MSM transmission (S. flexneri5a) does not. Strikingly,Shigellaserotypes which establish persistent infection fail to promote macrophage cell deathin vivo. We conclude that zebrafish can be a valuable platform to illuminate host and pathogen factors underlying the establishment of persistent infection withShigellain humans.HighlightsShigellacan establish persistent infection in zebrafishEstablishment of persistent infectionin vivodepends onShigellaserotypeThe same serotypes establishing persistent infection in zebrafish are prevalent in a patient group in whom persistent infection is observedShigellaserotypes which establish persistent infection fail to promote macrophage cell deathin vivoIn BriefIn high-income countries, sexual transmission among men who have sex with men (MSM) is the dominant cause of domesticShigellatransmission. Torracaet al. discover that three serotypes ofShigellaassociated with MSM transmission also persist in zebrafish. These results indicate thatShigellaserotypes associated with MSM transmission can establish carriage in the host, and highlight the use of zebrafish infection to studyShigellapersistent infection in humans.