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Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics
Viridans group streptococci (VGS), especially the Streptococcus mitis-oralis subgroup, are pivotal pathogens in a variety of invasive endovascular infections, including “toxic shock” in neutropenic cancer patients and infective endocarditis (IE). Previously, we showed that the serial in vitro passag...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460094/ https://www.ncbi.nlm.nih.gov/pubmed/32824132 http://dx.doi.org/10.3390/antibiotics9080520 |
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author | Mishra, Nagendra N. Tran, Truc T. Arias, Cesar A. Seepersaud, Ravin Sullam, Paul M. Bayer, Arnold S. |
author_facet | Mishra, Nagendra N. Tran, Truc T. Arias, Cesar A. Seepersaud, Ravin Sullam, Paul M. Bayer, Arnold S. |
author_sort | Mishra, Nagendra N. |
collection | PubMed |
description | Viridans group streptococci (VGS), especially the Streptococcus mitis-oralis subgroup, are pivotal pathogens in a variety of invasive endovascular infections, including “toxic shock” in neutropenic cancer patients and infective endocarditis (IE). Previously, we showed that the serial in vitro passage of S. mitis-oralis strains in sublethal daptomycin (DAP) resulted in rapid, high-level and stable DAP-resistance (DAP-R), which is accompanied by distinct changes in several genotypic and phenotypic signatures: (1) the disappearance of two key membrane phospholipids, phosphatidylglycerol (PG) and cardiolipin (CL); (2) increased membrane fluidity; (3) increased positive surface charge; (4) single nucleotide polymorphisms (SNPs) in two loci involved in CL biosynthesis (pgsA; cdsA); and (5) DAP hyperaccumulation. The current study examined these same metrics following in vitro serial DAP passages of a separate well-characterized S. mitis-oralis bloodstream isolate (SF100). Although some metrics seen in prior DAP post-passage strains were recapitulated with SF100 (e.g., pgsA SNPs, enhanced membrane fluidity), we observed the following major differences (comparing the parental versus post-passage variant): (1) no change in PG content; (2) reduced, but not absent, CL, with enhancement in phosphatidic acid (PA) content; (3) an unusual pattern of CL localization; (4) significantly decreased positive surface charge; (5) no difference in DAP accumulation; and (6) no cdsA SNPs. Thus, S. mitis-oralis strains are not “pre-programmed” phenotypically and/or genotypically to adapt in an identical manner during the evolution of the DAP-R. |
format | Online Article Text |
id | pubmed-7460094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74600942020-09-02 Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics Mishra, Nagendra N. Tran, Truc T. Arias, Cesar A. Seepersaud, Ravin Sullam, Paul M. Bayer, Arnold S. Antibiotics (Basel) Article Viridans group streptococci (VGS), especially the Streptococcus mitis-oralis subgroup, are pivotal pathogens in a variety of invasive endovascular infections, including “toxic shock” in neutropenic cancer patients and infective endocarditis (IE). Previously, we showed that the serial in vitro passage of S. mitis-oralis strains in sublethal daptomycin (DAP) resulted in rapid, high-level and stable DAP-resistance (DAP-R), which is accompanied by distinct changes in several genotypic and phenotypic signatures: (1) the disappearance of two key membrane phospholipids, phosphatidylglycerol (PG) and cardiolipin (CL); (2) increased membrane fluidity; (3) increased positive surface charge; (4) single nucleotide polymorphisms (SNPs) in two loci involved in CL biosynthesis (pgsA; cdsA); and (5) DAP hyperaccumulation. The current study examined these same metrics following in vitro serial DAP passages of a separate well-characterized S. mitis-oralis bloodstream isolate (SF100). Although some metrics seen in prior DAP post-passage strains were recapitulated with SF100 (e.g., pgsA SNPs, enhanced membrane fluidity), we observed the following major differences (comparing the parental versus post-passage variant): (1) no change in PG content; (2) reduced, but not absent, CL, with enhancement in phosphatidic acid (PA) content; (3) an unusual pattern of CL localization; (4) significantly decreased positive surface charge; (5) no difference in DAP accumulation; and (6) no cdsA SNPs. Thus, S. mitis-oralis strains are not “pre-programmed” phenotypically and/or genotypically to adapt in an identical manner during the evolution of the DAP-R. MDPI 2020-08-15 /pmc/articles/PMC7460094/ /pubmed/32824132 http://dx.doi.org/10.3390/antibiotics9080520 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mishra, Nagendra N. Tran, Truc T. Arias, Cesar A. Seepersaud, Ravin Sullam, Paul M. Bayer, Arnold S. Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics |
title | Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics |
title_full | Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics |
title_fullStr | Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics |
title_full_unstemmed | Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics |
title_short | Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics |
title_sort | strain-specific adaptations of streptococcus mitis-oralis to serial in vitro passage in daptomycin (dap): genotypic and phenotypic characteristics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460094/ https://www.ncbi.nlm.nih.gov/pubmed/32824132 http://dx.doi.org/10.3390/antibiotics9080520 |
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