Bibliographic Details
Title: |
Strain-Specific Adaptations of Streptococcus mitis-oralis to Serial In Vitro Passage in Daptomycin (DAP): Genotypic and Phenotypic Characteristics |
Authors: |
Nagendra N. Mishra, Truc T. Tran, Cesar A. Arias, Ravin Seepersaud, Paul M. Sullam, Arnold S. Bayer |
Source: |
Antibiotics, Vol 9, Iss 8, p 520 (2020) |
Publisher Information: |
MDPI AG, 2020. |
Publication Year: |
2020 |
Collection: |
LCC:Therapeutics. Pharmacology |
Subject Terms: |
Streptococcus mitis-oralis, daptomycin resistance, Therapeutics. Pharmacology, RM1-950 |
More Details: |
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. |
Document Type: |
article |
File Description: |
electronic resource |
Language: |
English |
ISSN: |
2079-6382 |
Relation: |
https://www.mdpi.com/2079-6382/9/8/520; https://doaj.org/toc/2079-6382 |
DOI: |
10.3390/antibiotics9080520 |
Access URL: |
https://doaj.org/article/1f1e2931e6924dde9f18c87453c56496 |
Accession Number: |
edsdoj.1f1e2931e6924dde9f18c87453c56496 |
Database: |
Directory of Open Access Journals |