CIPROFLOXACIN-RESISTANT HAEMOPHILUS-INFLUENZAE STRAINS POSSESS MUTATIONS IN ANALOGOUS POSITIONS OF GYRA AND PARC

The nucleotide sequences of the quinolone resistance-determining regio ns of the gyrA and parC genes from five ciprofloxacin-resistant strain s of Haemophilus influenzae (MICs, 2 to 32 mu g/ml) isolated from pati ents with cystic fibrosis and three ciprofloxacin-susceptible strains of H., influenzae (MICs, less than or equal to 0.1 mu g/ml) were deter mined. Four of the five resistant strains possessed at least one amino acid substitution in each of the GyrA and ParC fragments studied. The mutations identified in GyrA were a serine at residue 84 (Ser-84) to Leu or Tyr and Asp-88 to Asn or Tyr. ParC mutations were in positions exactly analogous to those identified in GyrA, namely, Ser-84 to Ile a nd Glu-88 to Lys. The Glu 88 to Lys ParC substitution was identified o nly in high-level ciprofloxacin-resistant strains. These mutations hav e been shown to be the origin of the observed resistance after transfo rmation into ciprofloxacin-susceptible H. influenzae isolates. These r esults suggest that H. influenzae isolates require at least one amino acid substitution in both GyrA and ParC in order to attain significant levels of resistance to quinolones.