title: A Salmonella protein that is required for resistance to antimicrobial peptides and transport of potassium.
abstract: The ability of invading pathogens to proliferate within host tissues requires the capacity to resist the killing effects of a wide variety of host defense molecules. sap mutants of the facultative intracellular parasite Salmonella typhimurium exhibit hypersensitivity to antimicrobial peptides, cannot survive within macrophages in vitro and are attenuated for mouse virulence in vivo. We conducted a molecular genetic analysis of the sapG locus and showed that it encodes a product that is 99% identical to the NAD+ binding protein TrkA, a component of a low-affinity K+ uptake system in Escherichia coli. SapG exhibits similarity with other E. coli proteins implicated in K+ transport including KefC, a glutathione-regulated efflux protein, and Kch, a putative transporter similar to eukaryotic K+ channel proteins, sapG mutants were killed by the antimicrobial peptide protamine in the presence of both high and low K+, indicating that protamine hypersensitivity is not due to K+ starvation. Strains with mutations in sapG and either sapJ or the sapABCDF operon were as susceptible as sapG single mutants, suggesting that the proteins encoded by these loci participate in the same resistance pathway. SapG may modulate the activities of SapABCDF and SapJ to mediate the transport of peptides and potassium.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110.
authors.forename: C
authors.initials: C
authors.lastname: Parra-Lopez
authors.forename: R
authors.initials: R
authors.lastname: Lin
authors.forename: A
authors.initials: A
authors.lastname: Aspedon
authors.forename: E A
authors.initials: EA
authors.lastname: Groisman
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial / Q000235:genetics; D008555:Melitten / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D011479:Protamines / Q000494:pharmacology; D020917:Receptor, trkA; D011994:Recombinant Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D010455:Peptides; D011479:Protamines; D011994:Recombinant Proteins; D009243:NAD; D008555:Melitten; D020917:Receptor, trkA; D011188:Potassium