The Impact of Substitutions at Positions 1 and 8 of Fluoroquinolones on the Activity Against Mutant DNA Gyrases of <i>Salmonella</i> Typhimurium

Suwanthada, Pondpan; Kongsoi, Siriporn; Miura, Nami; Belotindos, Lawrence P.; Piantham, Chayada; Toyting, Jirachaya; Akapelwa, Mwangala L.; Pachanon, Ruttana; Koide, Kentaro; Kim, Hyun; Thapa, Jeewan; Nakajima, Chie; Suzuki, Yasuhiko

doi:10.1089/mdr.2023.0014

Cited by 3 publications

(1 citation statement)

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“…DNA gyrase supercoiling assays were conducted to assess the inhibitory effects of FQs, particularly ciprofloxacin hydrochloride and moxifloxacin hydrochloride, with or without QnrB19. FQ-inhibiting DNA supercoiling assays were performed using GyrA, GyrB, and 54nM of QnrB19 to evaluate IC 50 s of FQs following protocols described in previous studies. ,, Briefly, DNA gyrase buffer containing 35 mM Tris-HCl pH 7.5, 24 mM KCl, 4 mM MgCl 2 , 2 mM DTT, 1.8 mM spermidine, 6.5% glycerol, and 0.1 mg/mL of BSA was mixed with 1 mM ATP, 1.5 nM relaxed pBR322 DNA, 18 nM DNA gyrase subunits, 54nM QnrB19, and varying concentrations of FQs. The concentrations of ciprofloxacin hydrochloride used against DNA gyrase carrying GyrA WT , GyrA S83F , and GyrA D87N ranged from 0.02 to 5.12, 0.08 to 20.48, and 0.16 to 40.96 mg/L, respectively.…”

Section: Methodsmentioning

confidence: 99%

Interplay between Amino Acid Substitution in GyrA and QnrB19: Elevating Fluoroquinolone Resistance in Salmonella Typhimurium

Suwanthada,

Kongsoi,

Jayaweera

et al. 2024

ACS Infect. Dis.

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Globally, there have been increasing reports of antimicrobial resistance in nontyphoidal Salmonella (NTS), which can develop into severe and potentially life-threatening diarrhea. This study focuses on the synergistic effects of DNA gyrase mutations and plasmid-mediated quinolone resistance (PMQR) genes, specifically qnrB19, on fluoroquinolone (FQ) resistance in Salmonella Typhimurium. By utilizing recombinant mutants, GyrA S83F and GyrA D87N , and QnrB19's, we discovered a significant increase in fluoroquinolones resistance when QnrB19 is present. Specifically, ciprofloxacin and moxifloxacin's inhibitory concentrations rose 10-and 8-fold, respectively. QnrB19 was found to enhance the resistance capacity of mutant DNA gyrases, leading to high-level FQ resistance. Additionally, we observed that the ratio of QnrB19 to DNA gyrase played a critical role in determining whether QnrB19 could protect DNA gyrase against FQ inhibition. Our findings underscore the critical need to understand these resistance mechanisms, as their coexistence enables bacteria to withstand therapeutic FQ levels, posing a significant challenge to treatment efficacy.

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Section: Methodsmentioning

confidence: 99%