Mutations in cdsA and pgsA Correlate with Daptomycin Resistance in Streptococcus mitis and S. oralis

Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01531-18. doi: 10.1128/AAC.01531-18. Print 2019 Feb.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Cardiolipins / metabolism
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Daptomycin / pharmacology*
  • Drug Resistance, Bacterial / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Nucleotidyltransferases / genetics*
  • Phosphatidylglycerols / metabolism
  • Streptococcus mitis / drug effects
  • Streptococcus mitis / genetics*
  • Streptococcus mitis / isolation & purification
  • Streptococcus oralis / drug effects
  • Streptococcus oralis / genetics*
  • Streptococcus oralis / isolation & purification
  • Transferases (Other Substituted Phosphate Groups) / genetics*

Substances

  • Anti-Bacterial Agents
  • Cardiolipins
  • Phosphatidylglycerols
  • Nucleotidyltransferases
  • phosphatidate cytidylyltransferase
  • Transferases (Other Substituted Phosphate Groups)
  • CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase
  • Daptomycin