MUTATIONS RESPONSIBLE FOR REDUCED SUSCEPTIBILITY TO 4-QUINOLONES IN CLINICAL ISOLATES OF MULTIRESISTANT SALMONELLA-TYPHI IN INDIA

Twelve isolates of Salmonella typhi isolated in Vellore, India had red uced susceptibility to 4-quinolones (MIG of ciprofloxacin 0.256 mg/L). One isolate was isolated in 1992 but the remaining 11 were isolated i n 1994. The section of the gyrA gene from codons 24 to 185, which incl udes the ''Quinolone Resistance Determining Region'', was amplified by the polymerase chain reaction and, after separating the amplified str ands, the DNA was sequenced directly. In the one isolate from 1992, no alterations were seen in this region of gyrA, compared with the cipro floxacin-sensitive isolates and presumably decreased 4-quinolone susce ptibility resulted from reduced permeability of the cell outer membran e or another mechanism. In nine isolates from 1994, a substitution of phenylalanine for serine at position 83 of GyrA correlated with the de crease in 4-quinolone susceptibility. In the remaining two isolates, t he novel substitution of aspartate to tyrosine at position 87 was foun d; in one isolate this substitution was coupled with another substitut ion at position 83 but in the other it was not.