Mechanisms of typhoid toxin neutralization by antibodies targeting glycan receptor binding and nuclease subunits.

ABSTRACT: Nearly all clinical isolates of Salmonella Typhi, the cause of typhoid fever, are antibiotic resistant. All S. Typhi isolates secrete an A₂B₅ exotoxin called typhoid toxin to benefit the pathogen during infection. Here, we demonstrate that antibiotic-resistant S. Typhi secretes typhoid toxin continuously during infection regardless of antibiotic treatment. We characterize typhoid toxin antibodies targeting glycan-receptor-binding PltB or nuclease CdtB, which neutralize typhoid toxin in vitro and in vivo, as demonstrated by using typhoid toxin secreted by antibiotic-resistant S. Typhi during human cell infection and lethal dose typhoid toxin challenge to mice. TyTx11 generated in this study neutralizes typhoid toxin effectively

SUBMITTER: Ahn C 

PROVIDER: S-EPMC8169802 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature