A New Highly Conserved Antibiotic Sensing/Resistance Pathway in Firmicutes Involves an ABC Transporter Interplaying with a Signal Transduction System

Signal transduction systems and ABC transporters often contribute jointly to adaptive bacterial responses to environmental changes. In Bacillus subtilis, three such pairs are involved in responses to antibiotics: BceRSAB, YvcPQRS and YxdJKLM. They are characterized by a histidine kinase belonging to the intramembrane sensing kinase family and by a translocator possessing an unusually large extracytoplasmic loop. It was established here using a phylogenomic approach that systems of this kind are specific but widespread in Firmicutes, where they originated. The present phylogenetic analyses brought to light a highly dynamic evolutionary history involving numerous horizontal gene transfers, duplications and lost events, leading to a great variety of Bce-like repertories in members of this bacterial phylum. Based on these phylogenetic analyses, it was proposed to subdivide the Bce-like modules into six well-defined subfamilies. Functional studies were performed on members of subfamily IV comprising BceRSAB from B. subtilis, the expression of which was found to require the signal transduction system as well as the ABC transporter itself. The present results suggest, for the members of this subfamily, the occurrence of interactions between one component of each partner, the kinase and the corresponding translocator. At functional and/or structural levels, bacitracin dependent expression of bceAB and bacitracin resistance processes require the presence of the BceB translocator loop. Some other members of subfamily IV were also found to participate in bacitracin resistance processes. Taken together our study suggests that this regulatory mechanism might constitute an important common antibiotic resistance mechanism in Firmicutes. [Supplemental material is available online at http://www.genome.org.

Combined systems approaches reveal highly plastic responses to antimicrobial peptide challenge in Escherichia coli

Obtaining an in-depth understanding of the arms races between peptides comprising the innate immune response and bacterial pathogens is of fundamental interest and will inform the development of new antibacterial therapeutics. We investigated whether a whole organism view of antimicrobial peptide (AMP) challenge on Escherichia coli would provide a suitably sophisticated bacterial perspective on AMP mechanism of action. Selecting structurally and physically related AMPs but with expected differences in bactericidal strategy, we monitored changes in bacterial metabolomes, morphological features and gene expression following AMP challenge at sub-lethal concentrations. For each technique, the vast majority of changes were specific to each AMP, with such a plastic response indicating E. coli is highly capable of discriminating between specific antibiotic challenges. Analysis of the ontological profiles generated from the transcriptomic analyses suggests this approach can accurately predict the antibacterial mode of action, providing a fresh, novel perspective for previous functional and biophysical studies

Antimicrobial peptides produced by bacteria: The bacteriocins

Bacteriocins are the subset of antimicrobial peptides (AMPs) produced by bacteria. They are small amphipathic peptides that interact with bacterial membranes leading to cell death. Most of the best known are produced by lactic acid bacteria used as food fermentation starters, because of their potential use as food preservatives. Bacteriocins are divided into two groups: lantibiotics that present posttranslational condensation rings and unmodified peptides. The first are subdivided into elongated versus globular lantibiotics, while four subgroups are recognized among unmodified bacteriocins. The genetic organization is in clusters that may reside into plasmids or transposons, formed by the structural gene, the export and immunity determinants, the quorum sensing governing production and any modification genes. Bacteriocins are active at extremely low concentrations (nM range) due to a dual mode of action: (a) binding to the membrane phospholipids and (b) specific recognition of surface components, both of which collaborate in pore formation. Development of resistance to bacteriocins is very infrequent due to the presence of two targets and is usually due to unspecific modifications of the cell envelope. Bacteriocins are used as food preservatives, either after total or partial purification or as extracts of producing bacteria. In situ production is also used, with the advantage of producing early lysis of the starter bacteria and ripening acceleration of the fermented product. They may also form part of hurdle technologies and be incorporated into packaging systems to allow extended liberation. Medical and veterinary applications are in their infancy but good results have been obtained against infection by Gram-positive bacteria and Helicobacter pylori.Peer reviewe