Fitness and competitive growth advantage of new gentamicin-susceptible MRSA clones spreading in French hospitals

Abstract

Since 1991, new epidemic methicillin-resistant Staphylococcus aureus (MRSA) strains characterized by the unexpected reappearance of heterogeneous phenotypic expression of resistance to methicillin and by susceptibility to gentamicin and various other antibiotics (GS-MRSA) have been reported in France. GS-MRSA strains have progressively replaced MRSA clones expressing homogeneous resistance to methicillin and resistance to gentamicin (GR-MRSA). In this study, we investigated the physiological characteristics of these new clones. In particular, we evaluated and compared the maximal growth rate and the deduced generation times (related to fitness of strains) of the major French epidemic MRSA clones. The population studied consisted of 79 isolates including (i) GR-MRSA that comprised six different types on the basis of PFGE; (ii) GS-MRSA the majority of which clustered into two PFGE types, A1 (usually resistant to erythromycin) and B (usually susceptible to erythromycin); (iii) methicillin-susceptible S. aureus (MSSA). GS-MRSA-A1 and MSSA strains were shown to have a significant fitness benefit (about 20%) with shorter generation times (θ = 23.7 ± 0.1 and 22.9 ± 0.05 min, respectively) than GR-MRSA and GS-MRSA-B strains (θ = 30.3 ± 0.2 and 32.5 ± 0.5 min, respectively). These data suggest that a link exists between genetic patterns, resistance profiles and physiological properties. In vitro competitive experiments indicated that GS-MRSA- A1 strains were able to rapidly outgrow GR-MRSA strains. The growth advantage observed should be taken into account in understanding the spread of some new clones of MRSA.