Neisseria gonorrhoeae acquires mutations in analogous regions of gyrA and parC in fluoroquinolone‐resistant isolates

Molecular Microbiology - Tập 14 Số 2 - Trang 371-380 - 1994
Robert J. Belland1, Sandra G. Morrison2, C A Ison3, W M Huang4
1Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana 59840.
2Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana 59840, USA.
3Department of Medical Microbiology, Wright-Fleming Institute, St. Mary's Hospital Medical School, London W2 1PG, UK
4Department of Cellular, Viral, and Molecular Biology University of Utah Medical Center Salt Lake City, Utah 84132 USA

Tóm tắt

Summary Neisseria gonorrhoeae homologues of gyrA and parC have been identified using hybridization probes generated from conserved regions of diverse gyrA genes. These genes have been tentatively identified as gyrA and parC, based on predicted amino acid sequence homologies to known GyrA homologues from numerous bacterial species and to ParC from Escherichia coli and Salmonella typhimurium. The gyrA gene maps to a physical location distant from the gyrB locus on the gonococcal chromosome, which is similar to the situation found in E. coli. The parC gene is not closely linked (i.e. greater than 9 kb) to an identifiable parE gene in N. gonorrhoeae. The gonococcal GyrA is slightly larger than its E. coli homologue and contains several small insertions near the O‐terminus of the predicted open reading frame. A series of ciprofloxacin‐resistant mutants were selected by passage of N. gonorrhoeae on increasing concentrations of the antibiotic. Sequential passage resulted in the selection of isolates with minimum inhibitory concentrations approximately 10000‐fold higher than the parental strain. Mutations within gyrA resulted in low to moderate levels of resistance, while strains with high‐level resistance acquired analogous mutations in both gyrA and parC. Resistance mutations were readily transferred between N. gonorrhoeae strains by transformation. The frequencies of transformation, resulting in different levels of ciprofloxacin resistance, further support the notion that both gyrA and parC genes are invoived in the establishment of extreme levels of ciprofloxacin resistance.

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Molecular Microbiology

Tập 14 Số 2

371-380

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