Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical University, Changhuai Road 287, Bengbu, Anhui Province 233030, China.
Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Changhuai Road 287, Bengbu, Anhui Province 233030, China.
J Appl Microbiol. 2024 May 1;135(5). doi: 10.1093/jambio/lxae077.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections poses a significant threat to human health, necessitating urgent development of new antimicrobial agents. Silver nanoparticles (AgNPs), which are among the most widely used engineered nanomaterials, have been extensively studied. However, the impact of AgNPs on CRKP and the potential for drug resistance development remain inadequately explored.
In this study, broth dilution method was used to determine the minimum inhibitory concentration (MIC) was determined using the broth dilution method. Results indicated MIC values of 93.1 ± 193.3 µg ml-1 for AgNPs, 2.3 ± 5.1 µg ml-1 for AgNO3, and 25.1 ± 48.3 µg ml-1 for imipenem (IMI). The combined inhibitory effect of AgNPs and IMI on CRKP was assessed using the checkerboard method. Moreover, after 6-20 generations of continuous culture, the MIC value of AgNPs increased 2-fold. Compared to IMI, resistance of Kl. pneumoniae to AgNPs developed more slowly, with a higher fold increase in MIC observed after 20 generations. Whole-genome sequencing revealed four nonsynonymous single nucleotide polymorphism mutations in CRKP after 20 generations of AgNP treatment.
We have demonstrated that AgNPs significantly inhibit CRKP isolates and enhance the antibacterial activity of imipenem against Kl. pneumoniae. Although the development of AgNP resistance is gradual, continued efforts are necessary for monitoring and studying the mechanisms of AgNP resistance.
耐碳青霉烯类肺炎克雷伯菌（CRKP）感染对人类健康构成重大威胁，因此迫切需要开发新的抗菌药物。银纳米粒子（AgNPs）作为应用最广泛的工程纳米材料之一，已得到广泛研究。然而，AgNPs 对 CRKP 的影响以及产生耐药性的潜力仍未得到充分探索。
本研究采用肉汤稀释法测定最小抑菌浓度（MIC）。结果表明，AgNPs 的 MIC 值为 93.1±193.3µg ml-1，AgNO3 的 MIC 值为 2.3±5.1µg ml-1，亚胺培南（IMI）的 MIC 值为 25.1±48.3µg ml-1。采用棋盘法评估 AgNPs 与 IMI 联合对 CRKP 的抑制作用。此外，经过 6-20 代连续培养后，AgNPs 的 MIC 值增加了 2 倍。与 IMI 相比，肺炎克雷伯菌对 AgNPs 的耐药性发展较慢，在 20 代后观察到 MIC 值的倍数增加更高。全基因组测序显示，经过 20 代 AgNP 处理后，CRKP 中有 4 个非同义单核苷酸突变。
我们证明了 AgNPs 可显著抑制 CRKP 分离株，并增强亚胺培南对肺炎克雷伯菌的抗菌活性。尽管 AgNP 耐药性的发展是渐进的，但仍需持续监测和研究 AgNP 耐药机制。
