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Contributions of the σ W , σ M and σ X regulons to the lantibiotic resistome of B acillus subtilis
Author(s) -
Kingston Anthony W.,
Liao Xiaojie,
Helmann John D.
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12380
Subject(s) - lantibiotics , lipid ii , nisin , teichoic acid , biology , bacillus subtilis , operon , bacteriocin , biochemistry , lipoteichoic acid , cell envelope , lanthionine , peptidoglycan , regulon , lactococcus lactis , flippase , cell wall , microbiology and biotechnology , peptide , bacteria , escherichia coli , membrane , phospholipid , gene , staphylococcus aureus , lactic acid , genetics , antimicrobial , phosphatidylserine
Summary In B acillus subtilis , the extracytoplasmic function ( ECF ) σ factors σ M , σ W and σ X all contribute to resistance against lantibiotics. Nisin, a model lantibiotic, has a dual mode of action: it inhibits cell wall synthesis by binding lipid II , and this complex also forms pores in the cytoplasmic membrane. These activities can be separated in a nisin hinge‐region variant ( N 20 P M 21 P ) that binds lipid II , but no longer permeabilizes membranes. The major contribution of σ M to nisin resistance is expression of ltaSa , encoding a stress‐activated lipoteichoic acid synthase, and σ X functions primarily by activation of the dlt operon controlling d ‐alanylation of teichoic acids. Together, σ M and σ X regulate cell envelope structure to decrease access of nisin to its lipid II target. In contrast, σ W is principally involved in protection against membrane permeabilization as it provides little protection against the nisin hinge region variant. σ W contributes to nisin resistance by regulation of a signal peptide peptidase ( SppA ), phage shock proteins ( PspA and YvlC , a PspC homologue) and tellurite resistance related proteins ( YceGHI ). These defensive mechanisms are also effective against other lantibiotics such as mersacidin, gallidermin and subtilin and comprise an important subset of the intrinsic antibiotic resistome of B . subtilis .