Small Colony Mutants of Staphylococcus aureus Allow Selection of Gyrase-Mediated Resistance to Dual-Target Fluoroquinolones

XIAO SU, PAN; PENELOPE HAMLYN,; TALENS VISCONTI, RAQUEL; FABIANA L. ALOVERO Ó F. L. ALOVERO; RUBEN HILARIO, MANZO; L MARK, FISHER

AMER SOC MICROBIOLOGY

Año: 2002 vol. 46 p. 2498 - 2498

luoroquinolones acting equally through DNA gyrase and topoisomerase IV in vivo are considered desirable in requiring two target mutations for emergence of resistant bacteria. To investigate this idea, we have studied the response of Staphylococcus aureus RN4220 to stepwise challenge with sparfloxacin,a known dual-target agent, and with NSFQ-105, a more potent sulfanilyl fluoroquinolone that behaves similarly. First-step mutants were obtained with both drugs but only at the MIC. These mutants exhibited distinctive small-colony phenotypes and two- to fourfold increases in MICs of NSFQ-105, sparfloxacin, and ciprofloxacin . No changes were detected in the quinolone resistance-determining regions of gyrA, grlA , or grlB gene. Quinolone-induced small-colony mutants shared the delayed coagulase response but not the requirement for menadione, or thymidine characteristic of small-colony variants, a subpopulation of S.aureus that is often defective in electron transport. Second-step mutants s