Phenotypic and genetic changes associated with the seesaw effect in MRSA strain N315 in a bioreactor model.

Objectives: Over the past decade, daptomycin treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections has led to the emergence of daptomycin nonsusceptible (DAP-NS) MRSA strains and a subsequent interest in combinatorial antibiotic therapies. We investigated the phenotypic and genetic changes associated with the seesaw effect, which describes the correlation between daptomycin resistance and increased β-lactam susceptibility in DAP-NS MRSA and the reverse phenomenon of DAP-NS strains acquiring renewed susceptibility to daptomycin after β-lactam exposure.

Methods: A continuous bioreactor model was used to study the effects of incremental doses of daptomycin followed by oxacillin on MRSA strain N315.