Structural and Biochemical Analysis of E. coli ABC Transporters Implicated in Antimicrobial Peptide Resistance.

Cationic antimicrobial peptides (CAMPs) are a key component of the innate immune system of many organisms, including humans. They target invading pathogens in a variety of ways often integrating into, and permeabilising, bacterial cell membranes and causing cell death. In response, bacteria have developed a variety of CAMP resistance mechanisms, including those based on ATP-binding cassette (ABC) transporters such as Sap and Yej, which are the subject of studies described herein. ABC importers use an extracellular substrate binding protein (SBP) to recognise substrates and deliver them to a cognate membrane complex for uptake into the cell. A primary aim of this study was to unravel the structural basis of CAMP binding by the SBPs, SapA and YejA. CAMPs are larger than conventional peptides handled by ABC transporters and usually contain secondary structure.