Distinct immunity protein families mediate compartment-specific neutralization of a bacterial toxin.

ABSTRACT: Staphylococcus aureus utilizes a type VII secretion system (T7SS) to secrete antibacterial toxins targeting competitor bacteria. EsxX is a T7SS substrate protein harboring an N-terminal LXG domain, which is secreted by ST398 strains. We demonstrate that the EsxX C terminus is a membrane-depolarizing toxin with a glycine zipper motif. EsxX is profoundly toxic to bacteria, displaying toxicity from both cytoplasmic and extracellular compartments. A pair of polytopic membrane proteins, ExiCD, protects cells from intoxication by extracellular EsxX. By contrast, a distinct soluble heterodimer, ExiAB, neutralizes cytoplasmic EsxX by sequestration of its glycine zipper motif in a binding groove on ExiB. exiA-exiB co-occur with esxX, consistent with protection from self-toxicity prior to EsxX secre

SUBMITTER: Alcock F 

PROVIDER: S-EPMC12744356 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature