Molecular genetic analysis of a locus required for resistance to antimicrobial peptides in Salmonella typhimurium.

Abstract

The innate immunity of vertebrates and invertebrates to microbial infection is mediated in part by small cationic peptides with antimicrobial activity. Successful pathogens have evolved mechanisms to withstand the antibiotic activity of these molecules. We have isolated a set of genes from Salmonella typhimurium which are required for virulence and resistance to the antimicrobial peptides melittin and protamine. Sequence analysis of a 5.7 kb segment from the wild‐type plasmid conferring resistance to protamine contained five open reading frames: sapA, sapB, sapC, sapD and sapF, organized in an operon structure and transcribed as a 5.3 kb mRNA. SapD and SapF exhibited similarity with the ‘ATP binding cassette’ family of transporters including the bacterial Opp and SpoOK, involved in the uptake of oligopeptides; the yeast STE6, necessary for the export of a peptide pheromone; and the mammalian mdr, which mediates resistance to chemotherapeutic agents in cancer cells. SapA showed identity with other periplasmic solute binding proteins involved in peptide transport. The SapABCDF system constitutes a novel transporter for enteric bacteria and the first one harboring a periplasmic component with a role in virulence.

Capsular Antigen Fraction 1 and Pla Modulate the Susceptibility of Yersinia pestis to Pulmonary Antimicrobial Peptides Such as Cathelicidin

“…An alternative explanation for the in vivo resistance of Y. pestis to CAMPs might be the activation of novel bacterial resistance genes (5,41). Oligopeptide transporters have been shown to be involved in bacterial resistance to CAMPs in Enterobacteriaceae and other gram-negative bacteria (39,44). It is thought that these transporters "inactivate" the membrane-active CAMPs by directing them to the bacterial cytoplasm, where they are inactivated by proteases.…”

Bacterial peptide transporters: Messengers of nutrition to virulence

“…63, 64 The probable mechanism behind this kind of resistance is that the antimicrobial peptides are transported inside cytoplasm, away from their targets and exposed to digestion inside the cytoplasm. The YejABEF operon also plays role in the virulence of S. Typhimurium in mouse model.…”

Peptides and ATP binding cassette peptide transporters

“…This operon consists of five open reading frames: sapA, sapB, sapC, sapD and sapF, and the system exhibits similarity with the ABC transporter superfamily. The substrate binding protein SapA has highest identity with receptor proteins involved in peptide transport [39]. The role of the sap operon in virulence has recently been questioned, because E. coli with an increased K + uptake capacity are less sensitive to protamine irrespective of whether a function Sap system is present.…”