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

Truc T. Tran, Nagendra N. Mishra, Ravin Seepersaud, Lorena Diaz, Rafael Rios, An Q. Dinh, Cristina Garcia-de-la-Maria, Michael J. Rybak, Jose M. Miro, Samuel A. Shelburne, Paul M. Sullam, Arnold S. Bayer, Cesar A. Arias

Research output: Contribution to journalArticle

1 Citation (Scopus)

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-3phosphatidyltransferase). 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.

Original languageEnglish (US)
Article numbere01531-18
JournalAntimicrobial Agents and Chemotherapy
Volume63
Issue number2
DOIs
StatePublished - Feb 2019

Fingerprint

Streptococcus mitis
Daptomycin
phosphatidate cytidylyltransferase
Mutation
Cardiolipins
Cytidine Diphosphate Diglycerides
Cell Membrane
Viridans Streptococci
Phosphatidylglycerols
Enzymes

Keywords

  • CdsA
  • Daptomycin resistance
  • PgsA
  • Streptococcus mitis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Tran, T. T., Mishra, N. N., Seepersaud, R., Diaz, L., Rios, R., Dinh, A. Q., ... Arias, C. A. (2019). Mutations in cdsA and pgsA Correlate with Daptomycin Resistance in Streptococcus mitis and S. Oralis. Antimicrobial Agents and Chemotherapy, 63(2), [e01531-18]. https://doi.org/10.1128/AAC.01531-18

Mutations in cdsA and pgsA Correlate with Daptomycin Resistance in Streptococcus mitis and S. Oralis. / Tran, Truc T.; Mishra, Nagendra N.; Seepersaud, Ravin; Diaz, Lorena; Rios, Rafael; Dinh, An Q.; Garcia-de-la-Maria, Cristina; Rybak, Michael J.; Miro, Jose M.; Shelburne, Samuel A.; Sullam, Paul M.; Bayer, Arnold S.; Arias, Cesar A.

In: Antimicrobial Agents and Chemotherapy, Vol. 63, No. 2, e01531-18, 02.2019.

Research output: Contribution to journalArticle

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 2019, 'Mutations in cdsA and pgsA Correlate with Daptomycin Resistance in Streptococcus mitis and S. Oralis', Antimicrobial Agents and Chemotherapy, vol. 63, no. 2, e01531-18. https://doi.org/10.1128/AAC.01531-18
Tran, Truc T. ; Mishra, Nagendra N. ; Seepersaud, Ravin ; Diaz, Lorena ; Rios, Rafael ; Dinh, An Q. ; Garcia-de-la-Maria, Cristina ; Rybak, Michael J. ; Miro, Jose M. ; Shelburne, Samuel A. ; Sullam, Paul M. ; Bayer, Arnold S. ; Arias, Cesar A. / Mutations in cdsA and pgsA Correlate with Daptomycin Resistance in Streptococcus mitis and S. Oralis. In: Antimicrobial Agents and Chemotherapy. 2019 ; Vol. 63, No. 2.
@article{a7c37a17187e4810a7a7728087320444,
title = "Mutations in cdsA and pgsA Correlate with Daptomycin Resistance in Streptococcus mitis and S. Oralis",
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-3phosphatidyltransferase). 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, Daptomycin resistance, PgsA, Streptococcus mitis",
author = "Tran, {Truc T.} and Mishra, {Nagendra N.} and Ravin Seepersaud and Lorena Diaz and Rafael Rios and Dinh, {An Q.} and Cristina Garcia-de-la-Maria and Rybak, {Michael J.} and Miro, {Jose M.} and Shelburne, {Samuel A.} and Sullam, {Paul M.} and Bayer, {Arnold S.} and Arias, {Cesar A.}",
year = "2019",
month = "2",
doi = "10.1128/AAC.01531-18",
language = "English (US)",
volume = "63",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "2",

}

TY - JOUR

T1 - Mutations in cdsA and pgsA Correlate with Daptomycin Resistance in Streptococcus mitis and S. Oralis

AU - Tran, Truc T.

AU - Mishra, Nagendra N.

AU - Seepersaud, Ravin

AU - Diaz, Lorena

AU - Rios, Rafael

AU - Dinh, An Q.

AU - Garcia-de-la-Maria, Cristina

AU - Rybak, Michael J.

AU - Miro, Jose M.

AU - Shelburne, Samuel A.

AU - Sullam, Paul M.

AU - Bayer, Arnold S.

AU - Arias, Cesar A.

PY - 2019/2

Y1 - 2019/2

N2 - 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-3phosphatidyltransferase). 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.

AB - 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-3phosphatidyltransferase). 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.

KW - CdsA

KW - Daptomycin resistance

KW - PgsA

KW - Streptococcus mitis

UR - http://www.scopus.com/inward/record.url?scp=85060797527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060797527&partnerID=8YFLogxK

U2 - 10.1128/AAC.01531-18

DO - 10.1128/AAC.01531-18

M3 - Article

C2 - 30509945

AN - SCOPUS:85060797527

VL - 63

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 2

M1 - e01531-18

ER -