Open AccessShigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence
Author(s) -
Vincenzo Torraca,
Myrsini Kaforou,
Jayne Watson,
Gina Duggan,
Hazel Guerrero-Gutierrez,
Sina Krokowski,
Michael Hollinshead,
Tom Clarke,
Rafal Mostowy,
Gillian S. Tomlinson,
Vanessa SanchoShimizu,
Abigail Clements,
Serge Mostowy
Publication year - 2019
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008006
Subject(s) - shigella sonnei , microbiology and biotechnology , phagolysosome , bacillary dysentery , shigella flexneri , biology , virulence , shigellosis , shigella , antigen , immunology , virology , dysentery , phagocytosis , bacteria , escherichia coli , salmonella , biochemistry , phagosome , genetics , gene
Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S . flexneri , especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish ( Danio rerio ) model of Shigella infection, we discover that S . sonnei is more virulent than S . flexneri in vivo . Whole animal dual-RNAseq and testing of bacterial mutants suggest that S . sonnei virulence depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show in vivo using zebrafish and ex vivo using human neutrophils that S . sonnei O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables S . sonnei to resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of S . sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal dose of S . sonnei are protected against a secondary lethal dose of S . sonnei in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against S . sonnei . Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasing S . sonnei burden in developing countries.