ABC transporters of antimicrobial peptides in Firmicutes bacteria – phylogeny, function and regulation

Antimicrobial peptides (AMPs) are a group of antibiotics that mainly target the cell wall of Gram-positive bacteria. Resistance is achieved by a variety of mechanisms including target alterations, changes in the cell's surface charge, expression of immunity peptides or by dedicated ABC transporters. The latter often provide the greatest level of protection. Apart from resistance, ABC transporters are also required for the export of peptides during biosynthesis. In this review the different AMP transporters identified to date in Firmicutes bacteria were classified into five distinct groups based on their domain architecture, two groups with a role in biosynthesis, and three involved in resistance. Comparison of the available information for each group regarding function, transport mechanism and gene regulation revealed distinguishing characteristics as well as common traits. For example, a strong correlation between transporter group and mode of gene regulation was observed, with three different types of two-component systems as well as XRE family transcriptional regulators commonly associated with individual transporter groups. Furthermore, the presented summary of the state-of-the-art on AMP transport in Firmicutes bacteria, discussed in the context of transporter phylogeny, provides insights into the mechanisms of substrate translocation and how this may result in resistance against compounds that bind extracellular targets.