title: Novel mechanism for nisin resistance via proteolytic degradation of nisin by the nisin resistance protein NSR.
abstract: Nisin is a 34-residue antibacterial peptide produced by Lactococcus lactis that is active against a wide range of gram-positive bacteria. In non-nisin-producing L. lactis, nisin resistance could be conferred by a specific nisin resistance gene (nsr), which encodes a 35-kDa nisin resistance protein (NSR). However, the mechanism underlying NSR-mediated nisin resistance is poorly understood. Here we demonstrated that the protein without the predicted N-terminal signal peptide sequence, i.e., NSRSD, could proteolytically inactivate nisin in vitro by removing six amino acids from the carboxyl "tail" of nisin. The truncated nisin (nisin(1-28)) displayed a markedly reduced affinity for the cell membrane and showed significantly diminished pore-forming potency in the membrane. A 100-fold reduction of bactericidal activity was detected for nisin(1-28) in comparison to that for the intact nisin. In vivo analysis indicated that NSR localized on the cell membrane and endowed host strains with nisin resistance by degrading nisin as NSRSD did in vitro, whereas NSRSD failed to confer resistance upon the host strain. In conclusion, we showed that NSR is a nisin-degrading protease. This NSR-mediated proteolytic cleavage represents a novel mechanism for nisin resistance in non-nisin-producing L. lactis.
authors.affiliation: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhizeng
authors.initials: Z
authors.lastname: Sun
authors.forename: Jin
authors.initials: J
authors.lastname: Zhong
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Liang
authors.forename: Jiale
authors.initials: J
authors.lastname: Liu
authors.forename: Xiuzhu
authors.initials: X
authors.lastname: Chen
authors.forename: Liandong
authors.initials: L
authors.lastname: Huan
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D013294:Lactococcus lactis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009561:Nisin / Q000378:metabolism* / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021382:Protein Sorting Signals
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D021382:Protein Sorting Signals; D009561:Nisin; D010447:Peptide Hydrolases