TY - JOUR
T1 - Strain-specific adaptations of streptococcus mitis-oralis to serial in vitro passage in daptomycin (DAP)
T2 - Genotypic and phenotypic characteristics
AU - Mishra, Nagendra N.
AU - Tran, Truc T.
AU - Arias, Cesar A.
AU - Seepersaud, Ravin
AU - Sullam, Paul M.
AU - Bayer, Arnold S.
N1 - Funding Information:
Funding: Cubist Pharmaceuticals (21272-01) and The Lundquist Institute-Harbor UCLA Intramural Research Grant 531604-01-01 to N.N.M.; National Institutes of Health (1R01130056-01 to A.S.B.; NIAID K24 AI121296, R01 AI134637 and R01 AI148342 to C.A.A.; K08 AI113317 to T.T.T., and R01 AI41513 to P.M.S.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - Daptomycin resistance
KW - Streptococcus mitis-oralis
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U2 - 10.3390/antibiotics9080520
DO - 10.3390/antibiotics9080520
M3 - Article
AN - SCOPUS:85089704919
VL - 9
SP - 1
EP - 10
JO - Antibiotics
JF - Antibiotics
SN - 2079-6382
IS - 8
M1 - 520
ER -