Heterogeneous oxacillin-resistant phenotypes and production of PBP2A by oxacillin-susceptible/mecA-positive MRSA strains from Africa

J Antimicrob Chemother. 2016 Oct;71(10):2804-9. doi: 10.1093/jac/dkw209. Epub 2016 Jun 7.

Abstract

Objectives: Recent surveillance of MRSA colonizing patients and healthcare workers in two African countries (Angola and São Tomé and Príncipe) reported the frequent recovery of oxacillin-susceptible MRSA (OS-MRSA): Staphylococcus aureus strains that gave positive results with the mecA DNA probe, but had low oxacillin MIC values characteristic of susceptible S. aureus. This apparent dissociation of the drug-resistant phenotype from mecA-the primary genetic determinant of resistance-prompted us to perform a more detailed analysis on nine of the African OS-MRSA strains.

Methods: Oxacillin MIC values were determined by Etest and population analysis profiles with and without induction of the stringent stress response by mupirocin. Biochemical profiling using SDS-PAGE followed by western blotting was used for the detection of PBP2A protein produced.

Results: Cultures of the African MRSA strains (ST88-IVa and ST8-V) showed heterogeneous oxacillin resistance in which the majority of cells exhibited low oxacillin MICs (≤0.75 mg/L), but highly resistant subpopulations were also present with oxacillin MIC values up to several hundred mg/L and with frequencies of 10(-4) to 10(-6). The same strains after induction of the stringent stress response by mupirocin 'converted' the heterogeneous phenotypes into a more homogeneous and higher level resistance. After induction by oxacillin and mupirocin, each of the nine African OS-MRSA strains produced PBP2A-the protein product of mecA.

Conclusions: The resistant phenotype of OS-MRSA resembles the phenotypes of historically early MRSA clones. The nature of genetic determinants responsible for the heterogeneous phenotypes of OS-MRSA remains to be determined.

Publication types

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

MeSH terms

  • Africa / epidemiology
  • Angola / epidemiology
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / biosynthesis*
  • Bacterial Proteins / genetics
  • Drug Resistance, Multiple, Bacterial / genetics
  • Electrophoresis, Polyacrylamide Gel
  • Epidemiological Monitoring
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification*
  • Methicillin-Resistant Staphylococcus aureus / metabolism
  • Microbial Sensitivity Tests
  • Oxacillin / pharmacology*
  • Penicillin-Binding Proteins / biosynthesis*
  • Penicillin-Binding Proteins / genetics
  • Phenotype
  • Staphylococcal Infections / epidemiology
  • Staphylococcal Infections / microbiology
  • beta-Lactam Resistance / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Penicillin-Binding Proteins
  • mecA protein, Staphylococcus aureus
  • Oxacillin