Effect of WQ-3334 on Campylobacter jejuni carrying a DNA gyrase with dominant amino acid substitutions conferring quinolone resistance

Miura-Ajima, Nami; Suwanthada, Pondpan; Kongsoi, Siriporn; Kim, Hyun; Pachanon, Ruttana; Koide, Kentaro; Mori, Shigetarou; Thapa, Jeewan; Nakajima, Chie; Suzuki, Yasuhiko

doi:10.1016/j.jiac.2024.04.002

Cited by 1 publication

(2 citation statements)

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“…Furthermore, it has been observed that IC 50 values tend to be higher than MICs. 32,33 The IC 50 is determined from in vitro tests that access the direct interactions among DNA gyrase, the examined drugs, and QnrB19. In live bacterial cells, factors such as drug accumulation and permeability are crucial for demonstrating inhibitory activity, leading to a high concentration of the drugs inside the cell.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Although IC 50 values cannot be directly translated to minimum inhibitory concentrations (MICs), previous studies , have demonstrated a positive correlation between these values either in NTS or other bacteria. Furthermore, it has been observed that IC 50 values tend to be higher than MICs. , The IC 50 is determined from in vitro tests that access the direct interactions among DNA gyrase, the examined drugs, and QnrB19. In live bacterial cells, factors such as drug accumulation and permeability are crucial for demonstrating inhibitory activity, leading to a high concentration of the drugs inside the cell .…”

Section: Discussionmentioning

confidence: 99%

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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: ■ Discussionmentioning

confidence: 99%