title: Cell envelope stress response in cell wall-deficient L-forms of Bacillus subtilis.
abstract: L-forms are cell wall-deficient bacteria that can grow and proliferate in osmotically stabilizing media. Recently, a strain of the Gram-positive model bacterium Bacillus subtilis was constructed that allowed controlled switching between rod-shaped wild-type cells and corresponding L-forms. Both states can be stably maintained under suitable culture conditions. Because of the absence of a cell wall, L-forms are known to be insensitive to β-lactam antibiotics, but reports on the susceptibility of L-forms to other antibiotics that interfere with membrane-anchored steps of cell wall biosynthesis are sparse, conflicting, and strongly influenced by strain background and method of L-form generation. Here we investigated the response of B. subtilis to the presence of cell envelope antibiotics, with regard to both antibiotic resistance and the induction of the known LiaRS- and BceRS-dependent cell envelope stress biosensors. Our results show that B. subtilis L-forms are resistant to antibiotics that interfere with the bactoprenol cycle, such as bacitracin, vancomycin, and mersacidin, but are hypersensitive to nisin and daptomycin, which both affect membrane integrity. Moreover, we established a lacZ-based reporter gene assay for L-forms and provide evidence that LiaRS senses its inducers indirectly (damage sensing), while the Bce module detects its inducers directly (drug sensing).
authors.affiliation: Department Biology I, Ludwig-Maximilians-University Munich, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Wolf
authors.forename: Patricia
authors.initials: P
authors.lastname: Domínguez-Cuevas
authors.forename: Richard A
authors.initials: RA
authors.lastname: Daniel
authors.forename: Thorsten
authors.initials: T
authors.lastname: Mascher
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D001414:Bacitracin / Q000494:pharmacology; D001430:Bacteriocins / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000502:physiology; D017576:Daptomycin / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D007740:L Forms / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007763:Lac Operon; D008563:Membrane Lipids / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000235:genetics; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C490532:LiaRS protein, Bacillus subtilis; D008563:Membrane Lipids; D010455:Peptides; C069959:mersacidin; D001414:Bacitracin; D014640:Vancomycin; D017576:Daptomycin