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Cell Envelope Stress Response in Cell Wall-Deficient L-Forms of Bacillus subtilis

Lookup NU author(s): Dr Patricia Dominguez Cuevas, Dr Richard DanielORCiD


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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 beta-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).

Publication metadata

Author(s): Wolf D, Dominguez-Cuevas P, Daniel RA, Mascher T

Publication type: Article

Publication status: Published

Journal: Antimicrobial Agents and Chemotherapy

Year: 2012

Volume: 56

Issue: 11

Pages: 5907-5915

Print publication date: 01/11/2012

ISSN (print): 0066-4804

ISSN (electronic): 1098-6596

Publisher: American Society for Microbiology


DOI: 10.1128/AAC.00770-12


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Funder referenceFunder name
Marie Curie Intra-European Fellowship
Marie Curie Short Term Fellowship
UK Biotechnology and Biological Sciences Research Council grant
MA2873/1-3DFG grant