Mutations responsible for reduced susceptibility to 4-quinolones in clinical isolates of multi-resistant Salmonella typhi in India

• Published in: Journal of antimicrobial chemotherapy Vol. 37; no. 5; pp. 891 - 900
• Main Authors: Brown, J. C., Shanahan, P. M. A., Jesudason, M. V., Thomson, C. J., Amyes, S. G. B.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.1996
• Subjects: Amino Acid Sequence; Bacteriology; Base Sequence; Biological and medical sciences; Ciprofloxacin - pharmacology; DNA Gyrase; DNA Topoisomerases, Type II - drug effects; DNA Topoisomerases, Type II - genetics; Drug Resistance, Microbial - genetics; Fundamental and applied biological sciences. Psychology; Genetics; Humans; India; Microbial Sensitivity Tests; Microbiology; Molecular Sequence Data; Mutation; Nalidixic Acid - pharmacology; Ofloxacin - pharmacology; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Quinolones - pharmacology; Salmonella typhi; Salmonella typhi - drug effects; Asia; India; Resistance; Antibiotic; Fluoroquinolone derivative; Salmonella typhi; Bacteria; Mutation; Antibacterial agent; Genome; Mechanism of action; Enterobacteriaceae
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/37.5.891

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.