Antibiotic-induced protein mislocalization drives hypervesiculation in Salmonella

Non-lethal cephalexin exposure in Salmonella drives robust hypervesiculation by disrupting the inner membrane barrier, enabling aberrant PBP5–ACP interactions at vesicle emergence sites.

• Why it matters: OMVs normally exclude cytosolic proteins because the inner membrane spatial barrier prevents cross-compartment interactions; antibiotic envelope stress may override this unresolved mechanism.
• What they did: Salmonella treated with non-lethal cephalexin showed PBP3 inhibition and PBP5 accumulation, with PBP5 relocating to lateral sites linked to MV emergence; cryogenic electron microscopy detected inner membrane perturbation and ACP mislocalization.
• The result: The PBP5–ACP complex promoted PBP5 accumulation, periplasmic crowding, progressive weakening of outer membrane peptidoglycan tethering, and ultimately MV formation, implying compartment disruption can drive non-canonical protein interactions.

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