Host Adaptations of the <i>Salmonella</i> Typhi Typhoid Toxin and Its Orthologue from a Nontyphoidal <i>Salmonella</i>

Abstract

Typhoidal and nontyphoidal Salmonellae (NTS) cause typhoid fever and gastroenteritis respectively in humans. Typhoid toxin from typhoidal Salmonella contributes to typhoid disease progression and chronic infection, but little is known about its orthologue from NTS. We found that these two Salmonella toxins do not cause similar toxicities in vivo. The altered virulence outcomes are due to the altered glycan binding preferences of these two toxins, which are correlated to the glycan expression profiles of target host cells at the primary infection or intoxication sites of their associated bacteria. The co-crystal structures of the glycan-receptor binding PltB subunits of the toxins bound to specific glycan receptor moieties explain how PltBs of these two toxins display markedly different glycan binding preferences and contribute to the subsequent virulence outcomes. We also revealed that administration of either Javiana toxin or S. Javiana into an animal model provides cross-reactive protection for typhoid-related illnesses and mortality.