Mutations in cdsA and pgsA Correlate With Daptomycin Resistance in S. mitis/oralis [Mechanisms of Resistance]

We investigated the ability of several recent clinical viridans group streptococci (VGS) bloodstream isolates (S. mitis/oralis sub-group) from daptomycin (DAP)-naïve patients to develop DAP resistance in vitro. All strains rapidly developed high-level and stable DAP-resistance. Substitutions in two enzymes involved in the cardiolipin biosynthesis pathway were identified: CdsA (phosphatidate cytidylyltransferase) and/or PgsA (CDP-diacylglycerol-glycerol-3-phosphate-3-phosphatidyltransferase). These mutations were associated with complete disappearance of phosphatidylglycerol and cardiolipin from cell membranes. DAP interactions with the cell membrane differed between isolates with PgsA vs CdsA substitutions.

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