Streptococcus mitis and S. oralis Lack a Requirement for CdsA, the Enzyme Required for Synthesis of Major Membrane Phospholipids in Bacteria

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dc.contributor.ORCID0000-0002-7343-9271 (Palmer, KL)en_US
dc.contributor.authorAdams, Hannah M.en_US
dc.contributor.authorJoyce, Luke R.en_US
dc.contributor.authorGuan, Ziqiangen_US
dc.contributor.authorAkins, Ronda L.en_US
dc.contributor.authorPalmer, Kelli L.en_US
dc.contributor.utdAuthorAdams, Hannah M.en_US
dc.contributor.utdAuthorJoyce, Luke R.en_US
dc.contributor.utdAuthorAkins, Ronda L.en_US
dc.contributor.utdAuthorPalmer, Kelli L.en_US
dc.date.accessioned2018-06-01T16:33:11Z
dc.date.available2018-06-01T16:33:11Z
dc.date.created2017-02-21en_US
dc.date.issued2018-06-01
dc.descriptionIncludes supplementary materialen_US
dc.description.abstractSynthesis and integrity of the cytoplasmic membrane are fundamental to cellular life. Experimental evolution studies have hinted at unique physiology in the Gram-positive bacteria Streptococcus mitis and S. oralis. These organisms commonly cause bacteremia and infectious endocarditis (IE) but are rarely investigated in mechanistic studies of physiology and evolution. Unlike in other Gram-positive pathogens, high-level (MIC ≥ 256 mu g/ml) daptomycin resistance rapidly emerges in S. mitis and S. oralis after a single drug exposure. In this study, we found that inactivating mutations in cdsA are associated with high-level daptomycin resistance in S. mitis and S. oralis IE isolates. This is surprising given that cdsA is an essential gene for life in commonly studied model organisms. CdsA is the enzyme responsible for the synthesis of CDP-diacylglycerol, a key intermediate for the biosynthesis of all major phospholipids in prokaryotes and most anionic phospholipids in eukaryotes. Lipidomic analysis by liquid chromatography-mass spectrometry (LC-MS) showed that daptomycin-resistant strains have an accumulation of phosphatidic acid and completely lack phosphatidylglycerol and cardiolipin, two major anionic phospholipids in wild-type strains, confirming the loss of function of CdsA in the daptomycin-resistant strains. To our knowledge, these daptomycin-resistant streptococci represent the first model organisms whose viability is CdsA independent. The distinct membrane compositions resulting from the inactivation of cdsA not only provide novel insights into the mechanisms of daptomycin resistance but also offer unique opportunities to study the physiological functions of major anionic phospholipids in bacteria.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.identifier.bibliographicCitationAdams, Hannah M., Luke R. Joyce, Ziqiang Guan, Ronda L. Akins, et al. 2017. "Streptococcus mitis and S. oralis lack a requirement for CdsA, the enzyme required for synthesis of major membrane phospholipids in bacteria." Antimicrobial Agents and Chemotherapy 61(5), doi:10.1128/AAC.02552-16en_US
dc.identifier.issn0066-4804en_US
dc.identifier.issue5en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/5820
dc.identifier.volume61en_US
dc.language.isoenen_US
dc.publisherAmer Soc Microbiologyen_US
dc.relation.urihttp://dx.doi.org/10.1128/AAC.02552-16
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2017 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceAntimicrobial Agents and Chemotherapy
dc.subjectViridans Streptococcien_US
dc.subjectStaphylococcus aureusen_US
dc.subjectPhosphatidate cytidylyltransferaseen_US
dc.subjectEscherichia colien_US
dc.subjectIn Vitro Techniquesen_US
dc.subjectPhosphatidic Acidsen_US
dc.subjectMicrobial Sensitivity Testsen_US
dc.subjectCardiolipin Synthetaseen_US
dc.subjectMicrobiologyen_US
dc.subjectDaptomycinen_US
dc.subjectStreptococcusen_US
dc.titleStreptococcus mitis and S. oralis Lack a Requirement for CdsA, the Enzyme Required for Synthesis of Major Membrane Phospholipids in Bacteriaen_US
dc.type.genrearticleen_US

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