Journal of Antimicrobial Chemotherapy (1996) 37, 891-900
© 1996 The British Society for Antimicrobial Chemotherapy
research-article |
Mutations responsible for reduced susceptibility to 4-quinolones in clinical isolates of multi-resistant Salmonella typhi in India
aDepartment of Medical Microbiology, The Medical School, University of Edinburgh Teviot Place, Edinburgh EH8 9AG, UK bDepartment of Medical Microbiology and Virology, Christian Medical College and Hospital Ida Scudder Road, Post Box No. 3, Vellore-632 004, India
Received 31 May 1995; returned 15 August 1995; accepted 15 December 1995
*Corresponding author
Twelve isolates of Salmonella typhi isolated in Vellore, India had reduced susceptibility to 4-quinolones (MIC of ciprofloxacin 0.256 mg/L). One isolate was isolated in 1992 but the remaining 11 were isolated in 1994. The section of the gyrA gene from codons 24 to 185, which includes the "Quinolone Resistance Determining Region", was amplified by the polymerase chain reaction and, after separating the amplified strands, the DNA was sequenced directly. In the one isolate from 1992, no alterations were seen in this region of gyrA, compared with the ciprofloxacin-sensitive isolates and presumably decreased 4-quinolone susceptibility resulted from reduced permeability of the cell outer membrane or another mechanism. In nine isolates from 1994, a substitution of phenylalanine for serine at position 83 of GyrA correlated with the decrease in 4-quinolone susceptibility. In the remaining two isolates, the novel substitution of aspartate to tyrosine at position 87 was found; in one isolate this substitution was coupled with another substitution at position 83 but in the other it was not.
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