Beta‐lactam Antibiotic Potentiation in MRSA Using Small Molecule Adjuvants

Abstract

Methicillin‐resistant Staphylococcus aureus (MRSA) is a major public health concern, as it has developed resistance to our existing arsenal of antibiotics. These bacteria also form robust biofilms that are evident in chronic infections. MRSA expresses a master regulator of both antibiotic resistance and biofilm formation. This protein, Stk1, is a eukaryotic‐like serine/threonine kinase. We have identified novel small molecule inhibitors of Stk1 which combat both antibiotic resistance and biofilm formation. We hypothesized that if cultures were treated with an inhibitor of Stk1 as an adjuvant, then changes in resistance genes would be observed. In order to determine if the adjuvant, the antibiotic oxacillin, and/or cotreatment changed mRNA levels in MRSA, total RNA was purified and RT‐qPCR was used to measure changes in gene expression in key genes such as blaI, blaZ, mecI, mecA and pbp2. We observed differential gene expression that helps explain at the transcript level why treatment of MRSA with an adjuvant is effective at potentiating beta‐lactam antibiotics.Support or Funding InformationResearch reported in this presentation was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number R15GM134503. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.