Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo, Japan.
Department of Bacteriology II, National Institute of Infectious Diseases, Musashimurayama, Japan.
Microbiol Spectr. 2024 Oct 3;12(10):e0432223. doi: 10.1128/spectrum.04322-23. Epub 2024 Aug 20.
Quinolone-resistant have been increasing worldwide. Quinolones exert their antibacterial activity by inhibiting DNA gyrase, but most of the isolates acquire quinolone resistance via an amino acid substitution in the A subunit of DNA gyrase. WQ-3810 is a quinolone antibiotic that has been reported to have high potency even to DNA gyrase with amino acid substitutions in several bacterial species; however, there was no information on . Hence, this study aimed to evaluate the activity of WQ-3810 to inhibit wild-type/mutant DNA gyrases of and the bacterial growth for accessing the potency for the treatment of quinolone-resistant infection. The inhibitory activity of WQ-3810 was assessed and compared with ciprofloxacin and nalidixic acid by calculating the half maximal inhibitory concentration (IC) against wild-type/mutant DNA gyrases. Next, the minimum inhibitory concentration (MIC) of WQ-3810 and five other quinolones was determined for including quinolone-resistant strains with amino acid substitutions in GyrA. Furthermore, the interaction between WQ-3810 and wild-type/mutant DNA gyrase was speculated using docking simulations. The IC of WQ-3810 against wild-type DNA gyrase was 1.03 µg/mL and not different from that of ciprofloxacin. However, those of WQ-3810 against mutant DNA gyrases were much lower than ciprofloxacin. The MICs of WQ-3810 ranged <0.016-0.031 µg/mL and were the lowest against both quinolone-susceptible and quinolone-resistant strains among the examined quinolones. The results obtained by the docking simulation agreed well with this observation. WQ-3810 seems to be a promising antimicrobial agent for the infections caused by quinolone-resistant .
WQ-3810, a relatively new quinolone antibiotic, demonstrates exceptional antibacterial properties against certain pathogens in previous studies. However, its efficacy against quinolone-resistant was not previously reported. The prevalence of quinolone-resistant as a cause of foodborne illnesses is increasing, prompting this investigation into the effectiveness of WQ-3810 as a countermeasure. This study revealed high inhibitory activity of WQ-3810 against both wild-type and mutant DNA gyrases of . WQ-3810 was equally efficacious as ciprofloxacin against wild-type DNA gyrases but showed superior effectiveness against mutant DNA gyrases. WQ-3810 also demonstrated the lowest minimum inhibitory concentrations, highlighting its enhanced potency against both susceptible and resistant strains of . This observation was well supported by the results of the in silico analysis. Consequently, WQ-3810 exhibits a higher level of bactericidal activity compared to existing quinolones in combating both susceptible and resistant isolates.
喹诺酮类耐药性已在全球范围内增加。喹诺酮类通过抑制 DNA 回旋酶发挥其抗菌活性，但大多数分离株通过 DNA 回旋酶 A 亚单位的氨基酸取代获得喹诺酮耐药性。WQ-3810 是一种喹诺酮类抗生素，据报道，即使在几种细菌物种中 DNA 回旋酶发生氨基酸取代，它也具有很高的效力;然而，对于 ，没有信息。因此，本研究旨在评估 WQ-3810 抑制 野生型/突变 DNA 回旋酶的活性和细菌生长，以评估其治疗喹诺酮类耐药 感染的潜力。通过计算对野生型/突变 DNA 回旋酶的半最大抑制浓度 (IC) 来评估和比较 WQ-3810 与环丙沙星和萘啶酸的抑制活性。接下来，确定 WQ-3810 和其他五种喹诺酮类药物的最小抑菌浓度 (MIC) ，包括 GyrA 中氨基酸取代的喹诺酮类耐药株。此外，使用对接模拟推测 WQ-3810 与野生型/突变 DNA 回旋酶的相互作用。WQ-3810 对野生型 DNA 回旋酶的 IC 为 1.03 µg/mL，与环丙沙星无差异。然而，WQ-3810 对突变 DNA 回旋酶的 IC 要低得多。WQ-3810 的 MIC 范围为 <0.016-0.031 µg/mL，在研究的喹诺酮类药物中，对所有测试的喹诺酮类敏感和耐药菌株均为最低。对接模拟的结果与这一观察结果非常吻合。WQ-3810 似乎是一种有前途的治疗喹诺酮类耐药 感染的抗菌药物。
在之前的研究中，一种相对较新的喹诺酮类抗生素 WQ-3810 对某些病原体表现出了极好的抗菌特性。然而，它对喹诺酮类耐药 的疗效以前没有报道过。由于食源性疾病的原因，喹诺酮类耐药 的流行率正在上升，这促使人们对 WQ-3810 作为一种对策的有效性进行了调查。本研究表明，WQ-3810 对 的野生型和突变型 DNA 回旋酶均具有高抑制活性。WQ-3810 对野生型 DNA 回旋酶的疗效与环丙沙星相当，但对突变型 DNA 回旋酶的疗效更好。WQ-3810 还表现出最低的最小抑菌浓度，突出了其对敏感和耐药菌株的增强效力。这一观察结果得到了计算机分析结果的很好支持。因此，与现有喹诺酮类药物相比，WQ-3810 对 敏感和耐药株均具有更高的杀菌活性。
