Fluoroquinolone resistance mutations in the parC, parE, and gyrA genes of clinical isolates of viridans group streptococci - PubMed (original) (raw)

Fluoroquinolone resistance mutations in the parC, parE, and gyrA genes of clinical isolates of viridans group streptococci

I González et al. Antimicrob Agents Chemother. 1998 Nov.

Abstract

The nucleotide sequences of the quinolone resistance-determining regions (QRDRs) of the parC and gyrA genes from seven ciprofloxacin-resistant (Cpr) isolates of viridans group streptococci (two high-level Cpr Streptococcus oralis and five low-level Cpr Streptococcus mitis isolates) were determined and compared with those obtained from susceptible isolates. The nucleotide sequences of the QRDRs of the parE and gyrB genes from the five low-level Cpr S. mitis isolates and from the NCTC 12261 type strain were also analyzed. Four of these low-level Cpr isolates had changes affecting the subunits of DNA topoisomerase IV: three in Ser-79 (to Phe or Ile) of ParC and one in ParE at a position not previously described to be involved in quinolone resistance (Pro-424). One isolate did not show any mutation. The two high-level Cpr S. oralis isolates showed mutations affecting equivalent residue positions of ParC and GyrA, namely, Ser-79 to Phe and Ser-81 to Phe or Tyr, respectively. The parC mutations were able to transform Streptococcus pneumoniae to ciprofloxacin resistance, while the gyrA mutations transformed S. pneumoniae only when mutations in parC were present. These results suggest that DNA topoisomerase IV is a primary target of ciprofloxacin in viridans group streptococci, DNA gyrase being a secondary target.

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Figures

FIG. 1

FIG. 1

Comparison of the nucleotide sequences of a region of parC containing the QRDRs from S. pneumoniae R6 (SPN R6) and various strains of S. oralis (SOR) and S. mitis (SMI). R1(3180C) is M22 transformed to the first level of ciprofloxacin resistance by use of the parC50-152 PCR product from strain 3180. Nucleotides and amino acids (italics) are numbered by taking the first parC nucleotide as nt 1 and the first ParC residue as number 1. The strand corresponding to the mRNA is shown. Only nucleotides different from those of S. pneumoniae R6 are indicated; dashes indicate nucleotide identity. Sense mutations and the corresponding amino acid changes are shown in bold. The deduced amino acid sequence of S. pneumoniae R6 is shown at the bottom, together with the amino acid changes observed in the indicated strains (in parentheses).

FIG. 2

FIG. 2

Comparison of the nucleotide sequences of a region of gyrA containing the QRDRs from S. pneumoniae R6 (SPN R6) and various strains of S. oralis (SOR) and S. mitis (SMI). R2(3429C/3180A) and R2(3429C/3870A) are R13429C (25) transformed to the second level of ciprofloxacin resistance by use of the gyrA46-172 PCR products from strains 3180 and 3870, respectively. Nucleotides and amino acids (italics) are numbered by taking the first gyrA nucleotide as nt 1 and the first GyrA residue as number 1. Symbols are as defined in the legend to Fig. 1.

FIG. 3

FIG. 3

Comparison of the nucleotide sequences of regions of parE (A) and gyrB (B) containing the QRDRs from S. pneumoniae R6 (SPN R6) and various strains of S. mitis (SMI). Nucleotides and amino acids (italics) are numbered by taking the first parE or gyrB nucleotide as nt 1 and the first ParE or GyrB residue as number 1. Symbols are as defined in the legend to Fig. 1.

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References

    1. Alcaide F, Carratala J, Liñares J, Gudiol F, Martín R. In vitro activities of eight macrolide antibiotics and RP-59500 (quinupristin-dalfopristin) against viridans group streptococci isolated from blood of neutropenic cancer patients. Antimicrob Agents Chemother. 1996;40:2117–2120. - PMC - PubMed
    1. Alcaide F, Liñares J, Pallarés R, Carratala J, Benítez M A, Gudiol F, Martín R. In vitro activity of 22 β-lactam antibiotics against penicillin-resistant and penicillin-susceptible viridans group streptococci isolated from blood. Antimicrob Agents Chemother. 1995;39:2243–2247. - PMC - PubMed
    1. Balas D, Férnandez-Moreira E, de la Campa A G. Molecular characterization of the gene encoding the DNA gyrase A subunit of Streptococcus pneumoniae. J Bacteriol. 1998;180:2854–2861. - PMC - PubMed
    1. Belland R, Morrison S, Ison C, Huang W. Neisseria gonorrhoeae acquires mutations in analogous regions of gyrA and parC in fluoroquinolone-resistant isolates. Mol Microbiol. 1994;14:371–380. - PubMed
    1. Bochud P Y, Eggiman P H, Calandra T H, Van Melle G, Saghafi L, Francioli P. Bacteremia due to viridans streptococcus in neutropenic patients with cancer: clinical spectrum and risk factors. Clin Infect Dis. 1994;18:25–31. - PubMed

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