Investigation of Nalidixic Acid Resistance Mechanism in Salmonella enterica Using Molecular Simulation Techniques

Abstract

The emergence of nalidixic acid-resistant strains of Salmonella typhimurium remains to be a major public health problem. In particular, the substitution of Asn in place of Asp at the 87 loci in the GyrA of S. typhimurium was experimentally stated for nalidixic acid resistance. However, the data on the possible mechanism of nalidixic acid resistance are limited. In this study, I-Mutant2.0 and DUET program were employed to explore the impact of mutation on the stability of GyrA protein. Subsequently, molecular simulation techniques were employed to provide detailed information on the nalidixic acid-resistant associates with the D87N mutation in the GyrA of S. typhimurium. The binding free energy data depicts that nalidixic acid forms stable complex only with native-type GyrA than mutant (D87N) type GyrA protein. Moreover, our results theoretically suggest that hydrogen bonding formed by the Arg91 is certainly responsible for the GyrA of S. typhimurium drug selectivity. It is hoped that these evidences are immensely important for the development of new antibiotic and to overcome the nalidixic acid resistance in the near future.

<i>Salmonella enterica</i> species isolated from local foodstuff and patients suffering from foodborne illness: Surveillance, antimicrobial resistance and molecular detection

“…The most common serovars transferred from animals to humans are Salmonella Enteritidis and Salmonella Typhimurium. Typhoid fever, paratyphoid fever, food poisoning and gastroenteritis are all disorders caused by Salmonella [43]. The 16S rRNA gene sequence is considered an important approach toward identification of bacterial genus, species, and sub-species, and was used in this study as a confirmatory detection test.…”

“…According to the researchers, antibiotic resistance in Salmonella spp. is mostly caused by mutations within the quinolone resistance-determining regions (QRDRs) of the target enzymes DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) [54].…”

Identification of NS2B-NS3 Protease Inhibitors for Therapeutic Application in ZIKV Infection: A Pharmacophore-Based High-Throughput Virtual Screening and MD Simulations Approaches

“…Efficacious drug discoveries necessitate intricated, expensive, and time-intensive processes. The e-pharmacophore-based high-throughput virtual screening holds the promising potential to identify clinically effective drugs at the cost of minimum time and expense [ 11 , 12 , 13 ]. The afore mentioned approach has precedence over other drug repurposing strategies as reported for several discoveries of specific inhibitors for the potential control of viral infections [ 14 , 15 ].…”

Investigations into the electronic properties of lorlatinib, an anti‐cancerous drug using DFT, wavefunction analysis and MD simulations

“…MD methods, for example, were employed to investigate the mechanism of nalidixic acid resistance and to determine the reason of oseltamivir resistance. [ 10,11 ] Lorlatinib is a third generation, ATP‐competitive small molecule tyrosine kinase inhibitor which shows success in clinical studies in lung cancer patients. [ 12 ] Lorlatinib is a macrocyclic molecule that has a new chemical structure that allows it to penetrate cells and block efflux.…”