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

ABSTRACT: Staphylococcus aureus utilises a type VII secretion system (T7SS) to secrete antibacterial toxins that target competitor bacteria. EsxX is a T7SS substrate protein secreted by ST398 strains that has an LXG domain at its N-terminus. Here we show that the EsxX C-terminus is a membrane-depolarising 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, protect cells from intoxication by extracellular EsxX. By contrast, a distinct soluble heterodimer, ExiAB, neutralises cytoplasmic EsxX by sequestration of its glycine zipper motif in a binding groove on ExiB. The exiA-exiB gene pair co-occur in staphylococcal genomes with esxX, invoking

SUBMITTER: Alcock F 

PROVIDER: S-EPMC12258717 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature