Nisin-induced changes inBacillusmorphology suggest a paradigm of antibiotic action

Abstract

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.cell wall ͉ electron microscopy ͉ bacterial morphology ͉ lantibiotic ͉ cell division

Reduced mucosal antimicrobial activity in Crohn's disease of the colon

“…Comparable changes were recently described for Bacillus subtilus treated with Nisin, a small cationic lanthionine antibiotic. 49 The antimicrobial activity of extracts from ulcerative colitis, with a tendency to increased activity compared with controls, clearly demonstrates that the pathogenic defect in ulcerative colitis is not mediated by the diminished synthesis of antimicrobial peptides as in Crohn's disease. In contrast to the almost sterile mucus of healthy controls, however, colonisation of the mucus with microorganisms is characteristic for both Crohn's disease and ulcerative colitis.…”

NsaRS is a cell-envelope-stress-sensing two-component system of Staphylococcus aureus

“…It functions by binding to the carbohydrate-phosphate moiety of the cell wall biosynthesis component lipid II (de Kruijff et al, 2008;Schneider & Sahl, 2010). By binding and sequestering lipid II, nisin blocks cell wall biosynthesis and can lead to delocalization of biosynthetic components and aberrant septum formation (Hasper et al, 2006;Hyde et al, 2006). Additionally, nisin is also believed to use this docking event with lipid II to engineer pore formation in the membranes of target cells.…”

Focal targeting by human β-defensin 2 disrupts localized virulence factor assembly sites in Enterococcus faecalis

“…However, some CAMPs have additional targets that facilitate their toxic effects (40). Particularly well studied are peptides that interact specifically with the peptidoglycan biosynthesis intermediate lipid II at high affinity, including the lantibiotic nisin, fungal defensin plectasin, human neutrophil peptides, and hBD3, allowing them to "dock" at sites of cell-wall synthesis resulting in the sequestration of lipid II away from its functional location and/or resulting in localized membrane pore formation (22,(41)(42)(43)(44)(45). Because nascent PG synthesis, and hence lipid II appearance, occurs in rings emanating from the septal area in ovococci such as E. faecalis, it would not be surprising for lipid II targeting CAMPs to localize to the septal area, as we observe.…”