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  • Title: Mutations in cdsA and pgsA Correlate with Daptomycin Resistance in Streptococcus mitis and S. oralis.
    Author: Tran TT, Mishra NN, Seepersaud R, Diaz L, Rios R, Dinh AQ, Garcia-de-la-Maria C, Rybak MJ, Miro JM, Shelburne SA, Sullam PM, Bayer AS, Arias CA.
    Journal: Antimicrob Agents Chemother; 2019 Feb; 63(2):. PubMed ID: 30509945.
    Abstract:
    We investigated the ability of several recent clinical viridans group streptococci (VGS) bloodstream isolates (Streptococcus mitis/S. oralis subgroup) from daptomycin (DAP)-naive 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, i.e., CdsA (phosphatidate cytidylyltransferase) and 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 in isolates with PgsA versus CdsA substitutions.
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