Native efflux pumps contribute resistance to antimicrobials of skin and the ability of Staphylococcus aureus to colonize skin

J Infect Dis. 2014 May 1;209(9):1485-93. doi: 10.1093/infdis/jit660. Epub 2013 Nov 26.


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.

Conclusion: Antibacterial fatty acids may be natural substrates of Tet38, which contributes to resistance and the ability of S. aureus to colonize skin.

Keywords: Fatty acid; NorC; S. aureus; Spermidine; Tet38; Tetracycline.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drug Resistance, Bacterial
  • Fatty Acids / pharmacokinetics
  • Fatty Acids / pharmacology
  • Gene Expression Regulation, Bacterial
  • Male
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Polyamines / pharmacokinetics
  • Polyamines / pharmacology
  • Skin / chemistry
  • Skin / microbiology
  • Staphylococcal Skin Infections / microbiology*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / metabolism*
  • Tetracycline / pharmacokinetics
  • Tetracycline / pharmacology


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Fatty Acids
  • Membrane Transport Proteins
  • Polyamines
  • Tetracycline