Repercussions on Quinolone Resemblance in Enterotoxigenic E. coli gyrA Mutants: Molecular Dynamics Simulations and Residue Interaction Network Analysis

Abstract

Regarding foreign travel, particularly to impoverished nations, travelers' diarrhea (TD) is one of the most significant global health challenges. The most common infection causing TD is enterotoxigenic Escherichia coli (ETEC). TD is extremely incapacitating, yet it also has a self-limiting effect. For TD patients, ciprofloxacin is one of the common quinolone medications. Finding new medications is urgently needed, though, due to the alarmingly high levels of antibiotic resistance. GyrA, which is only found in prokaryotes and is crucial for bacterial viability, is the pharmacological target of ciprofloxacin. Reduction in affinity for quinolones is explained by increasing quinolone resistance in vivo, which is linked to several mutations in the gyrA region that determines quinolone resistance. To gain insight into the molecular processes that underlie the drug resistance mechanism, we provide here, for the first time as far as we are aware, the structural and dynamic impacts of ETEC gyrA mutations on ciprofloxacin affinity relative to the wild-type protein. According to our simulations, mutations drastically change the global dominant motion pattern and the gyrA residue interaction network in the key domains peculiar to the N-terminal regions of gyrA. To treat drug-resistant bacterial illnesses, like TDs, this work offers crucial information for developing more effective anti-bacterial medicines with high ligand efficacy. Key words: Escherichia coli, ciprofloxacin, gyrA gene, MD simulations, mutation