Profiling the effect of nafcillin on HA-MRSA D592 using bacteriological and physiological media

Abstract

Staphylococcus aureus is a leading human pathogen associated with both hospital-acquired and community-acquired infections. The bacterium has steadily gained resistance to {beta}-lactams and other important first-line antibiotics culminating in its categorization as an urgent threat by the U.S. Centers for Disease Control and Prevention. Observations of a varying response to antimicrobial exposure as a function of media type has revealed that clinical susceptibility testing performed in standard bacteriological media might not adequately represent pharmacological responses in the patient. Such observations have encouraged research designed to identify media types that more closely mimic the in vivo environment. In this study, we examine the response of a hospital-acquired USA100 lineage methicillin-resistant, vancomycin-intermediate S. aureus (MRSA/VISA) strain (D592) to nafcillin in a bacteriological compared to a more physiological tissue culture-based medium. We performed multi-dimensional analysis including growth and bacterial cytological profiling, RNA sequencing, and exo-metabolomics measurements (both HPLC and LC/MS) to shed light on the media-dependent activity of the commonly prescribed {beta}-lactam antibiotic nafcillin. O_TBL View this table: org.highwire.dtl.DTLVardef@85b95borg.highwire.dtl.DTLVardef@14c1504org.highwire.dtl.DTLVardef@1f7e976org.highwire.dtl.DTLVardef@100598dorg.highwire.dtl.DTLVardef@1f770e9_HPS_FORMAT_FIGEXP M_TBL C_TBL