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

doi:10.1128/AAC.01531-18

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

Houston Methodist

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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 language	English (US)
Article number	e01531-18
Journal	Antimicrobial Agents and Chemotherapy
Volume	63
Issue number	2
DOIs	https://doi.org/10.1128/AAC.01531-18
State	Published - Feb 2019

Keywords

CdsA
Daptomycin resistance
PgsA
Streptococcus mitis

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

Divisions

Infectious Disease

Access to Document

10.1128/AAC.01531-18

Cite this

Tran, T. T., Mishra, N. N., Seepersaud, R., Diaz, L., Rios, R., Dinh, A. Q., Garcia-de-la-Maria, C., Rybak, M. J., Miro, J. M., Shelburne, S. A., Sullam, P. M., Bayer, A. S., & 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), Article e01531-18. https://doi.org/10.1128/AAC.01531-18

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

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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.\}",

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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.

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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

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

Abstract

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