title: Native efflux pumps contribute resistance to antimicrobials of skin and the ability of Staphylococcus aureus to colonize skin.
abstract: BACKGROUND
  Staphylococcus aureus colonizes skin in the presence of antimicrobial fatty acids and polyamines. The chromosomally encoded Tet38 efflux transporter confers resistance to tetracycline and fitness in abscesses, but its natural substrates and those of the Nor quinolone efflux pumps are unknown.
  
  
  METHODS
  Susceptibility of tet38 and other pump mutants to and pump gene induction by fatty acids and polyamines were compared. Transport of fatty acids by Tet38 was determined in membrane vesicles. Survival on skin was tested in an adapted mouse skin infection model.
  
  
  RESULTS
  The tet38 expression caused a 5- to 8-fold increase in resistance to palmitoleic and undecanoic acids but not polyamines. Subinhibitory concentrations of these fatty acids induced 4-fold increases in tet38 transcripts and competitively inhibited transport of Hoechst 33 342 dye in Tet38 membrane vesicles. Colonization of skin in BALB/c mice was decreased 5-fold in a Δtet38 mutant, which was complemented by plasmid-encoded tet38. Although polyamine minimum inhibitory concentrations (MICs) decreased 4-fold in a norC::cat mutant and increased 8-fold with norC overexpression, spermidine did not induce expression of norC and other pump genes, and norC::cat exhibited wild-type colonization.
  
  
  CONCLUSIONS
  Antibacterial fatty acids may be natural substrates of Tet38, which contributes to resistance and the ability of S. aureus to colonize skin.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Que Chi
authors.initials: QC
authors.lastname: Truong-Bolduc
authors.forename: Regis A
authors.initials: RA
authors.lastname: Villet
authors.forename: Zoe A
authors.initials: ZA
authors.lastname: Estabrooks
authors.forename: David C
authors.initials: DC
authors.lastname: Hooper
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D005227:Fatty Acids / Q000493:pharmacokinetics / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D011073:Polyamines / Q000493:pharmacokinetics / Q000494:pharmacology; D012867:Skin / Q000737:chemistry / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013752:Tetracycline / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005227:Fatty Acids; D026901:Membrane Transport Proteins; D011073:Polyamines; D013752:Tetracycline
keywords: Fatty acid; NorC; S. aureus; Spermidine; Tet38; Tetracycline