Nisin-induced changes in Bacillus morphology suggest a paradigm of antibiotic action

Nisin is a small cationic lanthionine antibiotic produced by Lactococcus lactis. During its antimicrobial action, it targets intermediates in the bacterial cell-wall biosynthesis, lipid II, and undecaprenyl pyrophosphate. Here, we report results from electron microscopic investigations of the effects of lethal nisin doses on Bacillus subtilis cell morphology. Bacterial membranes were permeabilized shortly after B. subtilis was incubated with nisin, but this did not lead to immediate cell death. Cell division, as well as other life functions, persisted over at least half an hour after nisin was added. Slower bacterial elongation, consistent with cell envelope inhibition and accelerated division, resulted in cell-length reduction. Abnormal morphogenesis near the division site suggests this to be the primary site of nisin action. Morphological changes are characteristic of deregulation of a filamentous cell envelope protein, Mbl, and the division-inhibiting Min system. We propose a previously undescribed model, in which the lethal action of nisin against B. subtilis starts with membrane permeabilization and is followed by accelerated cell division, cell envelope inhibition, and aberrant cell morphogenesis.