Contribution of mutations in gyrA and parC genes to fluoroquinolone resistance of mutants of Streptococcus pneumoniae obtained in vivo and in vitro

167Citations
Citations of this article
26Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

We have analyzed by gene amplification and sequencing mutations in the quinolone resistance-determining regions of the gyrA, gyrB, and parC genes of fluoroquinolone-resistant Streptococcus pneumoniae mutants obtained during therapy or in vitro. Mutations leading to substitutions in ParC were detected in the two mutants obtained in vivo, BM4203-R (substitution of a histidine for an aspartate at position 84 [Asp-84→His]; Staphylococcus aureus coordinates) and BM4204-R (Ser-80→Phe), and in two mutants obtained in vitro (Ser-80→Tyr). An additional mutant obtained in vitro, BM4205-R3, displayed a higher level of fluoroquinolone resistance and had a mutation in gyrA leading to a Ser-84→Phe change. We could not detect any mutation in the three remaining mutants obtained in vitro. Total DNA from BM4203-R, BM4204-R, and BM4205-R3 was used to transform S. pneumoniae CP1000 by selection on fluoroquinolones. For the parc mutants, transformants with phenotypes indistinguishable from those of the donors were obtained at frequencies (5 x 10-3 to 8 x 10-3) compatible with monogenic transformation. By contrast, transformants were obtained at a low frequency (4 x 10-5), compatible with the transformation of two independent genes, for the gyrA mutant. Resistant transformants of CP 1000 were also obtained with an amplified fragment of parC from BM4203-R and BM4204-R but not with a gyrA fragment from BM4205-R3. All transformants had mutations identical to those in the donors. These data strongly suggest that Parc is the primary target for fluoroquinolones in S. pneumoniae and that BM4205-R3 is resistant to higher levels of the drugs following the acquisition of two mutations, including one in gyrA.

Cite

CITATION STYLE

APA

Tankovic, J., Perichon, B., Duval, J., & Courvalin, P. (1996). Contribution of mutations in gyrA and parC genes to fluoroquinolone resistance of mutants of Streptococcus pneumoniae obtained in vivo and in vitro. Antimicrobial Agents and Chemotherapy, 40(11), 2505–2510. https://doi.org/10.1128/aac.40.11.2505

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free