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.
Keywords:
CdsA; PgsA; Streptococcus mitis; daptomycin resistance.
Copyright © 2019 American Society for Microbiology.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / pharmacology*
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Cardiolipins / metabolism
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Cell Membrane / genetics
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Cell Membrane / metabolism
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Daptomycin / pharmacology*
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Drug Resistance, Bacterial / genetics
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Humans
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Microbial Sensitivity Tests
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Nucleotidyltransferases / genetics*
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Phosphatidylglycerols / metabolism
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Streptococcus mitis / drug effects
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Streptococcus mitis / genetics*
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Streptococcus mitis / isolation & purification
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Streptococcus oralis / drug effects
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Streptococcus oralis / genetics*
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Streptococcus oralis / isolation & purification
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Transferases (Other Substituted Phosphate Groups) / genetics*
Substances
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Anti-Bacterial Agents
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Cardiolipins
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Phosphatidylglycerols
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Nucleotidyltransferases
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phosphatidate cytidylyltransferase
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Transferases (Other Substituted Phosphate Groups)
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CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase
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Daptomycin