Identification of Regions Important for Resistance and Signalling within the Antimicrobial Peptide Transporter BceAB of Bacillus subtilis

F. Kallenberg, S. Dintner, R. Schmitz, S. Gebhard

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Abstract

In the low-G+C-content Gram-positive bacteria, resistance to antimicrobial peptides is often mediated by so-called resistance modules. These consist of a two-component system and an ATP-binding cassette transporter and are characterized by an unusual mode of signal transduction where the transporter acts as a sensor of antimicrobial peptides, because the histidine kinase alone cannot detect the substrates directly. Thus, the transporters fulfill a dual function as sensors and detoxification systems to confer resistance, but the mechanistic details of these processes are unknown. The paradigm and best-understood example for this is the BceRS-BceAB module of Bacillus subtilis, which mediates resistance to bacitracin, mersacidin, and actagardine. Using a random mutagenesis approach, we here show that mutations that affect specific functions of the transporter BceAB are primarily found in the C-terminal region of the permease, BceB, particularly in the eighth transmembrane helix. Further, we show that while signaling and resistance are functionally interconnected, several mutations could be identified that strongly affected one activity of the transporter but had only minor effects on the other. Thus, a partial genetic separation of the two properties could be achieved by single amino acid replacements, providing first insights into the signaling mechanism of these unusual modules.
Original languageEnglish
Pages (from-to)3287-3297
JournalJournal of Bacteriology
Volume195
Issue number14
DOIs
Publication statusPublished - 15 Jul 2013

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Bacillus subtilis
Bacitracin
Peptides
Mutation
ATP-Binding Cassette Transporters
Membrane Transport Proteins
Base Composition
Gram-Positive Bacteria
Mutagenesis
Signal Transduction
Amino Acids
peptide permease
mersacidin
gardimycin
Histidine Kinase

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Identification of Regions Important for Resistance and Signalling within the Antimicrobial Peptide Transporter BceAB of Bacillus subtilis. / Kallenberg, F.; Dintner, S.; Schmitz, R.; Gebhard, S.

In: Journal of Bacteriology, Vol. 195, No. 14, 15.07.2013, p. 3287-3297.

Research output: Contribution to journalArticle

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