The BceRS two-component regulatory system induces expression of the bacitracin transporter, BceAB, in

Department of Molecular Biology, School of Health Sciences, Kyorin University, 476 Miyashita, Hachiouji, Tokyo 192-0005, Japan.
Molecular Microbiology (Impact Factor: 5.03). 09/2003; 49(4):1135-44. DOI: 10.1046/j.1365-2958.2003.03653.x
Source: PubMed

ABSTRACT BceA and bceB encode a nucleotide-binding domain (NBD) and membrane-spanning domain (MSD) subunit, respectively, of an ATP-binding cassette (ABC) transporter in Bacillus subtilis. Disruption of these genes resulted in hypersensitivity to bacitracin, a peptide antibiotic that is non-ribosomally synthesized in some strains of Bacillus. Northern hybridization analyses showed that expression of the bceAB operon is induced by bacitracin present in the growth medium. The bceRS genes encoding a two-component regulatory system are located immediately upstream of bceAB. Deletion analyses of the bceAB promoter together with DNase I footprinting experiments revealed that a sensor kinase, BceS, responds to extracellular bacitracin either directly or indirectly and transmits a signal to a cognate response regulator, BceR. The regulator binds directly to the upstream region of the bceAB promoter and upregulates the expression of bceAB genes. The bcrC gene product is additionally involved in bacitracin resistance. The expression of bcrC is dependent on the ECF sigma factors, sigmaM and sigmaX, but not on the BceRS two-component system. In view of these results, possible roles of BceA, BceB and BcrC in bacitracin resistance of B. subtilis 168 are discussed.

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    • "For example, the BceAB system of Bacillus subtilis confers resistance to bacitracin. A 143-fold increased sensitivity in B. subtilis 168 BceAB-defective mutants has been reported (Ohki et al., 2003). Inactivation of the homologous system ABC 09 of L. casei BL23 resulted in an increased sensitivity to bacitracin (2-fold), nisin (1.7-fold), plectasin (2-fold) and subtilin (2.5-fold) relative to the wild-type strain Fig. 1. A. Structural and compositional diversity of antimicrobial peptides. "
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    ABSTRACT: The Firmicutes constitute a phylum of bacteria that can be found in a wide variety of habitats, from soil to the gastrointestinal tract of animals, where they have to thrive in complex communities. Competition in these communities usually involves the production of compounds such as antimicrobial peptides (AMPs) to eliminate competitor organisms. Animals and plants also produce AMPs to control their associated microbiota. In turn, defence mechanisms have evolved to prevent the action of these compounds. The close association of some Firmicutes with humans as prominent pathogens or commensal organisms has driven a considerable research effort on defence mechanisms used by these bacteria against antimicrobial compounds. This review focuses on the most recent advances on two well-characterized defence mechanisms against AMPs: the modification of the cell wall by D-alanylation and the role of peptide antibiotic-specific adenosine triphosphate-binding cassette transporters.
    Environmental Microbiology 01/2014; 16(5). DOI:10.1111/1462-2920.12400 · 6.24 Impact Factor
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    • "FEMS Microbiol Lett 320 (2011) 33–39 c 2011 Federation of European Microbiological Societies Published by Blackwell Publishing Ltd. All rights reserved located (Ohki et al., 2003; Rietkötter et al., 2008 "
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    ABSTRACT: Bacterial two-component systems (TCSs) have been demonstrated to be associated with not only the expression of virulence factors, but also the susceptibility to antibacterial agents. In Staphylococcus aureus, 16 types of TCSs have been identified. We previously found that the inactivation of one uncharacterized TCS (designated as BceRS, MW gene ID: MW2545-2544) resulted in an increase in susceptibility to bacitracin. In this study, we focused on this TCS and tried to identify the TCS-controlled factors affecting the susceptibility to bacitracin. We found that two ABC transporters were associated with the susceptibility to bacitracin. One transporter designated as BceAB (MW2543-2542) is downstream of this TCS, while another (formerly designated as VraDE: MW2620-2621) is separate from this TCS. Both transporters showed homology with several bacitracin-resistance factors in Gram-positive bacteria. Inactivation of each of these two transporters increased the susceptibility to bacitracin. Expressions of these transporters were significantly increased by the addition of bacitracin, while this induction was not observed in the TCS-inactivated mutant. These results indicate that this TCS senses bacitracin, and also positively regulates the expression of two ABC transporters.
    FEMS Microbiology Letters 07/2011; 320(1):33-9. DOI:10.1111/j.1574-6968.2011.02291.x · 2.72 Impact Factor
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    • "In this study we have identified a conserved imperfect palindrome (CTTTCAA NN T/CTGTAAG) in the promoter regions of the braDE and vraDE operons and through a genetic approach, combining deletions and point mutations within this sequence, shown that it is essential for bacitracin-dependent induction and activation by BraSR (Fig. 4). Although the sequence of this operator site is strikingly similar to that reported for BceR of S. mutans, strongly suggesting it is indeed the BraR binding site, it shares no similarities with the binding site for BceR of B. subtilis (Ohki et al., 2003; Ouyang et al., 2010). The position of the likely BraR binding site, approximately 60 bp upstream from the transcription initiation sites of the braDE and vraDE operons (Fig. 4A), suggests that BraR is probably a Class I transcription activator, interacting with the a subunit of RNA polymerase (Ishihama, 1993). "
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    ABSTRACT: Two-component systems (TCSs) are key regulatory pathways allowing bacteria to adapt their genetic expression to environmental changes. Bacitracin, a cyclic dodecylpeptide antibiotic, binds to undecaprenyl pyrophosphate, the lipid carrier for cell wall precursors, effectively inhibiting peptidoglycan biosynthesis. We have identified a novel and previously uncharacterized TCS in the major human pathogen Staphylococcus aureus that we show to be essential for bacitracin and nisin resistance: the BraS/BraR system (Bacitracin resistance associated; SA2417/SA2418). The braRS genes are located immediately upstream from genes encoding an ABC transporter, accordingly designated BraDE. We have shown that the BraSR/BraDE module is a key bacitracin and nisin resistance determinant in S. aureus. In the presence of low antibiotic concentrations, BraSR activate transcription of two operons encoding ABC transporters: braDE and vraDE. We identified a highly conserved imperfect palindromic sequence upstream from the braDE and vraDE promoter sequences, essential for their transcriptional activation by BraSR, suggesting it is the likely BraR binding site. We demonstrated that the two ABC transporters play distinct and original roles in antibiotic resistance: BraDE is involved in bacitracin sensing and signalling through BraSR, whereas VraDE acts specifically as a detoxification module and is sufficient to confer bacitracin and nisin resistance when produced on its own. We show that these processes require functional BraD and VraD nucleotide-binding domain proteins, and that the large extracellular loop of VraE confers its specificity in bacitracin resistance. This is the first example of a TCS associated with two ABC transporters playing separate roles in signal transduction and antibiotic resistance.
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