title: Proteomic response of Bacillus subtilis to lantibiotics reflects differences in interaction with the cytoplasmic membrane.
abstract: Mersacidin, gallidermin, and nisin are lantibiotics, antimicrobial peptides containing lanthionine. They show potent antibacterial activity. All three interfere with cell wall biosynthesis by binding lipid II, but they display different levels of interaction with the cytoplasmic membrane. On one end of the spectrum, mersacidin interferes with cell wall biosynthesis by binding lipid II without integrating into bacterial membranes. On the other end of the spectrum, nisin readily integrates into membranes, where it forms large pores. It destroys the membrane potential and causes leakage of nutrients and ions. Gallidermin, in an intermediate position, also readily integrates into membranes. However, pore formation occurs only in some bacteria and depends on membrane composition. In this study, we investigated the impact of nisin, gallidermin, and mersacidin on cell wall integrity, membrane pore formation, and membrane depolarization in Bacillus subtilis. The impact of the lantibiotics on the cell envelope was correlated to the proteomic response they elicit in B. subtilis. By drawing on a proteomic response library, including other envelope-targeting antibiotics such as bacitracin, vancomycin, gramicidin S, or valinomycin, YtrE could be identified as the most reliable marker protein for interfering with membrane-bound steps of cell wall biosynthesis. NadE and PspA were identified as markers for antibiotics interacting with the cytoplasmic membrane.
authors.affiliation: Biology of Microorganisms, Ruhr University Bochum, Bochum, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Wenzel
authors.forename: Bastian
authors.initials: B
authors.lastname: Kohl
authors.forename: Daniela
authors.initials: D
authors.lastname: Münch
authors.forename: Nadja
authors.initials: N
authors.lastname: Raatschen
authors.forename: H Bauke
authors.initials: HB
authors.lastname: Albada
authors.forename: Leendert
authors.initials: L
authors.lastname: Hamoen
authors.forename: Nils
authors.initials: N
authors.lastname: Metzler-Nolte
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Sahl
authors.forename: Julia E
authors.initials: JE
authors.lastname: Bandow
mesh_terms: D001412:Bacillus subtilis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D001430:Bacteriocins / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D008564:Membrane Potentials / Q000187:drug effects; D009561:Nisin / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D020543:Proteome / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001430:Bacteriocins; D015415:Biomarkers; D010455:Peptides; D020543:Proteome; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; C057656:gallidermin; C069959:mersacidin; D009561:Nisin; C102526:nisin A; D011188:Potassium