Mutation in the Quinolone Resistance-Determining Region (QRDR) of the gyrA Gene in Ciprofloxacin-Resistant Staphylococcus aureus Quinolone Resistance-Determining Region (QRDR) of the gyrA Gene

Abstract

The emergence of fluoroquinolone-resistant Salmonella enterica serovar Typhi poses a serious public health challenge, particularly in developing countries where ciprofloxacin is commonly used for treatment. This study investigated mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene in ciprofloxacin-resistant S. typhi isolates obtained in Sokoto, Nigeria. Four previously identified ciprofloxacin-resistant clinical isolates were subjected to biochemical characterization, minimum inhibitory concentration (MIC) determination, polymerase chain reaction (PCR) amplification, and sequencing of the gyrA gene. MIC analysis revealed varying levels of resistance among the isolates, with values ranging from 2 µg/ml to 512 µg/ml. PCR amplification successfully detected the gyrA gene in all isolates, producing amplicons of approximately 318 base pairs. Sequencing analysis of the amplified gene showed 93% similarity with the reference sequence of Salmonella enterica serovar typhi strain CT18 from the NCBI database. A point mutation was identified at nucleotide position 249 within the QRDR, resulting in an amino acid substitution from Aspartate to Histidine. Structural analysis further indicated that this substitution occurs near the quinolone resistance-determining region, potentially affecting the interaction between DNA gyrase and ciprofloxacin. These findings suggest that mutations in the gyrA gene contribute to ciprofloxacin resistance in S. typhi isolates in Sokoto. Continuous surveillance and molecular characterization of resistant strains are essential to guide effective antimicrobial therapy and control the spread of resistant pathogens.