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Computational identification of novel natural inhibitors against triple mutant DNA gyrase A in fluoroquinolone-resistant Typhimurium.

Biochem Biophys Rep

March 2025

Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India.

The rising resistance to fluoroquinolones in Typhimurium poses a significant global health challenge. This computational research addresses the pressing need for new therapeutic drugs by utilizing various computational tools to identify potential natural compounds that can inhibit the triple mutant DNA gyrase subunit A enzyme, which is crucial in fluoroquinolone resistance. Initially, the three-dimensional structure of the wild-type DNA gyrase A protein was modeled using homology modeling, and followed by mutagenesis to create the clinically relevant triple mutant (SER83PHE, ASP87GLY, ALA119SER) DNA gyrase A protein structure.

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The WHO has compiled a list of pathogens that urgently require new antibiotics in response to the rising reports of antibiotic resistance and a diminished supply of new antibiotics. At the top of this list is fluoroquinolone-resistant , fluoroquinolone-resistant spp. and vancomycin-resistant .

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Background: Pseudomonas aeruginosa is a significant opportunistic pathogen, especially in hospital-acquired infections, with plasmid-mediated fluoroquinolone resistance posing a major healthcare threat. This research aimed to isolate fluoroquinolone-resistant P. aeruginosa from patients at Aleppo University Hospital, assess the prevalence of fluoroquinolone resistance, confirm molecular identity, identify plasmid-associated resistance genes, and investigate virulence factors.

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Background: Nemonoxacin is a new quinolone with an antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Certain sequence types (STs) have been emerging in Taiwan, including fluoroquinolone-resistant ST8/USA300. It's an urgent need to determine nemonoxacin susceptibility against ST8/USA300 and other emerging lineages, if any.

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