title: Structural Insights into the Fluoroquinolone Resistance Mechanism of Shigella flexneri DNA Gyrase and Topoisomerase IV.
abstract: Traveler's diarrhea (TD) is an important public health concern that can result from a variety of intestinal pathogens, including bacteria, parasites, and virus. A number of antibiotics are being used to cure TD, but due to widespread use of these antibiotics, the pathogens are becoming resistant to them. In this work, we performed docking studies of DNA gyraseA (GyrA) and topoisomerase IV (ParC) of Shigella flexneri and their mutants with two different fluoroquinolones, ciprofloxacin and norfloxacin, to understand their resistance mechanism at the structural level. S. flexneri strains with mutations at serine 83 to leucine and aspartic acid 87 to glutamate or asparagine of GyrA and that of serine 80 to isoleucine in ParC have decreased susceptibility to fluoroquinolones. This analysis revealed that interaction of ciprofloxacin/norfloxacin with all the mutants was weaker than the interaction of ciprofloxacin/norfloxacin with the wild type. This study highlights the importance of aspartic acid and serine in GyrA and that of serine in ParC, forming bonds with ciprofloxacin/norfloxacin, which may play a crucial role in antibiotic resistance. This work corelates very well with the experimental outcomes and gives a good explanation for fluoroquinolone resistance in S. flexneri.
authors: Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology , Waknaghat, Solan, India .
authors: Tamanna
authors: Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology , Waknaghat, Solan, India .
authors: Jayashree
authors: J
authors: Ramana
mesh_terms: D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001224:Aspartic Acid / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002939:Ciprofloxacin / Q000737:chemistry* / Q000494:pharmacology; D027081:DNA Gyrase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015870:Gene Expression; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D009154:Mutation; D009643:Norfloxacin / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D012763:Shigella flexneri / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D013816:Thermodynamics
chemical_list: D000900:Anti-Bacterial Agents; D001224:Aspartic Acid; D012694:Serine; D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D009643:Norfloxacin