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

• DOI: 10.1093/jac/dkw209
• Publication Date: 2016-06-09T00:08:46Z
• Authors: Marilyn Chung; Choon Keun Kim; Teresa Conceição; Marta Aires-De-Sousa; Hermínia De Lenca...; Alexander Tomasz
• Keywords: Methicillin-Resistant Staphylococcus aureus; 0301 basic medicine; Microbial Sensitivity Tests; Staphylococcal Infections; beta-Lactam Resistance; Anti-Bacterial Agents; 3. Good health; 03 medical and health sciences; Phenotype; Angola; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Africa; Epidemiological Monitoring; Humans; Penicillin-Binding Proteins; Electrophoresis, Polyacrylamide Gel; Oxacillin

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.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.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.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.