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Plasmid-mediated resistance to thrombin-induced platelet microbicidal protein in staphylococci: role of the qacA

L I Kupferwasser1, R A Skurray, M H Brown

  • 1Division of Adult Infectious Diseases, St. John's Cardiovascular Research Center, Harbor-UCLA Medical Center, Torrance, California 90509, USA. kupferwasser@hotmail.com

Antimicrobial Agents and Chemotherapy
|October 3, 1999
PubMed

Insights

The staphylococcal multidrug resistance gene qacA confers resistance to thrombin-induced platelet microbicidal protein 1 (tPMP-1). This finding reveals a novel mechanism for Staphylococcus aureus survival against this important antimicrobial peptide.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Thrombin-induced platelet microbicidal protein 1 (tPMP-1) is a cationic peptide crucial for innate immunity.
  • Staphylococcus aureus strains exhibiting in vitro resistance to tPMP-1 show enhanced survival in infections.
  • The precise mechanisms underlying S. aureus resistance to tPMP-1 remain incompletely understood.

Purpose of the Study:

  • To investigate whether the staphylococcal multidrug resistance gene qacA mediates resistance to the cationic antimicrobial peptide tPMP-1.
  • To elucidate the role of the qacA efflux pump in conferring resistance to tPMP-1.

Main Methods:

  • Introduction of staphylococcal plasmids encoding qacA into susceptible S. aureus strains.
  • Deletion analysis of the qacA gene region on the S. aureus multiresistance plasmid pSK1.
  • Assessment of tPMP-1 resistance levels in qacA-bearing and control strains.
  • Evaluation of cross-resistance to other cationic antimicrobial peptides.

Main Results:

  • Staphylococcal plasmids carrying the qacA gene conferred significant resistance to tPMP-1 in susceptible S. aureus.
  • Abolition of tPMP-1 resistance was observed when the qacA gene region was deleted from the pSK1 plasmid.
  • Resistance was peptide concentration-dependent and inoculum-independent.
  • No cross-resistance was observed to other structurally distinct cationic antimicrobial peptides.

Conclusions:

  • The staphylococcal multidrug resistance gene qacA is responsible for mediating in vitro resistance to the cationic antimicrobial peptide tPMP-1.
  • The qacA efflux pump plays a key role in the survival of S. aureus against tPMP-1.
  • This study identifies a novel function of the qacA gene in antimicrobial peptide resistance.

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