Strain-specific adaptations of streptococcus mitis-oralis to serial in vitro passage in daptomycin (DAP): genotypic and phenotypic characteristics



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Antibiotics, 2079-6382, Vol. 9, Nro. 8, 2020. p. 1-10

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Multidisciplinary Digital Publishing Institute (MDPI)

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Abstract:Viridans group streptococci (VGS), especially theStreptococcus mitis-oralissubgroup,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 theserialin vitropassage ofS. mitis-oralisstrains in sublethal daptomycin (DAP) resulted in rapid,high-level and stable DAP-resistance (DAP-R), which is accompanied by distinct changes in severalgenotypic and phenotypic signatures: (1) the disappearance of two key membrane phospholipids,phosphatidylglycerol (PG) and cardiolipin (CL); (2) increased membrane fluidity; (3) increased positivesurface 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 metricsfollowingin vitroserial DAP passages of a separate well-characterizedS. mitis-oralisbloodstreamisolate (SF100). Although some metrics seen in prior DAP post-passage strains were recapitulated withSF100 (e.g.,pgsASNPs, 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 notabsent, CL, with enhancement in phosphatidic acid (PA) content; (3) an unusual pattern of CLlocalization; (4) significantly decreased positive surface charge; (5) no difference in DAP accumulation;and (6) nocdsASNPs. Thus,S. mitis-oralisstrains are not “pre-programmed” phenotypically and/orgenotypically to adapt in an identical manner during the evolution of the DAP-R.

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Daptomycin resistance, Streptococcus mitis-oralis