title: Characterization of a regulatory network of peptide antibiotic detoxification modules in Lactobacillus casei BL23.
abstract: Two-component systems (TCS) are major signal transduction pathways that allow bacteria to detect and respond to environmental and intracellular changes. A group of TCS has been shown to be involved in the response against antimicrobial peptides (AMPs). These TCS are characterized by the possession of intramembrane-sensing histidine kinases, and they are usually associated with ABC transporters of the peptide-7 exporter family (Pep7E). Lactobacillus casei BL23 encodes two TCS belonging to this group (TCS09 and TCS12) that are located next to two ABC transporters (ABC09 and ABC12), as well as a third Pep7E ABC transporter not genetically associated with any TCS (orphan ABC). This study addressed the involvement of modules TCS09/ABC09 and TCS12/ABC12 in AMP resistance. Results showed that both systems contribute to L. casei resistance to AMPs, and that each TCS constitutes a functional unit with its corresponding ABC transporter. Analysis of transcriptional levels showed that module 09 is required for the induction of ABC09 expression in response to nisin. In contrast, module 12 controls a wider regulon that encompasses the orphan ABC, the dlt operon (d-alanylation of teichoid acids), and the mprF gene (l-lysinylation of phospholipids), thereby controlling properties of the cell envelope. Furthermore, the characterization of a dltA mutant showed that Dlt plays a major role in AMP resistance in L. casei. This is the first report on the regulation of the response of L. casei to AMPs, giving insight into its ability to adapt to the challenging environments that it encounters as a probiotic microorganism.
authors: Departamento de Biotecnología, Consejo Superior de Investigaciones Científicas, Paterna, Valencia, Spain.
authors: Ainhoa
authors: A
authors: Revilla-Guarinos
authors: Susanne
authors: S
authors: Gebhard
authors: Cristina
authors: C
authors: Alcántara
authors: Anna
authors: A
authors: Staron
authors: Thorsten
authors: T
authors: Mascher
authors: Manuel
authors: M
authors: Zúñiga
mesh_terms: D000222:Adaptation, Physiological; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001414:Bacitracin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D016384:Consensus Sequence; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D058685:Genetic Pleiotropy; D016680:Genome, Bacterial; D007780:Lacticaseibacillus casei / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009561:Nisin / Q000494:pharmacology; D009876:Operon; D011401:Promoter Regions, Genetic; D018085:Regulon; D013045:Species Specificity; D014158:Transcription, Genetic
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D001414:Bacitracin; D009561:Nisin