A
sitafloxacin regimen is highly effective on Mycoplasma genitalium
infections, including those caused by the mycoplasmas harboring mutant
topoisomerase IV with a
quinolone resistance-associated
amino acid change in ParC. In this study, we evaluated
sitafloxacin antimicrobial activities against M. genitalium, including the mycoplasmas with decreased susceptibilities to
quinolones, by determining minimum inhibitory concentrations (MICs) for the strain ATCC 33530 and its 3
ciprofloxacin-selected mutants, for which
ciprofloxacin MICs were 8-16 times higher than that for their parent strain. We also evaluated inhibitory activities against the target
enzymes of M. genitalium by determining concentrations required to inhibit 50% (IC50) of the supercoiling activity of the recombinant wild-type
DNA gyrase and the decatenating activities of the recombinant wild-type
topoisomerase IV and the 2 types of mutant
topoisomerase IV with a single
amino acid change in ParC.
Sitafloxacin MICs were 0.125 for the parent strain and 0.125-0.25 μg/ml for the mutants.
Sitafloxacin IC50s were 3.12 for the supercoiling activity of the wild-type
DNA gyrase and 2.98 μg/ml for the decatenating activity of the wild-type
topoisomerase IV. Its IC50s for the decatenating activity of the mutant
topoisomerase IV harboring an
amino acid change in ParC were 15.1 for Gly-81 → Cys and 7.92 μg/ml for Asp-87 → Tyr.
Sitafloxacin was highly active against
ciprofloxacin-selected mutants of M. genitalium and possessed intense inhibitory activities not only against wild-type
DNA gyrase and
topoisomerase IV but also against mutant
topoisomerase IV containing ParC with a
quinolone resistance-associated
amino acid change.
Sitafloxacin could be a promising agent for M. genitalium
infections.