Microbiology and Immunology Department, Faculty of Pharmacy, Zagazig University, Zagazig City, Egypt.
Microbiology and Immunology Department, Faculty of Pharmacy, Port Said University, Port Said City, Egypt.
BMC Microbiol. 2023 Aug 22;23(1):229. doi: 10.1186/s12866-023-02969-9.
The emergence of multidrug-resistant Klebsiella pneumoniae in hospitals represents a serious threat to public health. Infections caused by Klebsiella pneumoniae are widespread in healthcare institutions, mainly pneumonia, bloodstream infections, and infections affecting neonates in intensive care units; so, it is necessary to combat this pathogen with new strategies. Targeting virulence factors necessary to induce host damage and disease is a new paradigm for antimicrobial therapy with several potential benefits that could lead to decreased resistance.
The influence of metformin, N-acetylcysteine, and secnidazole on Klebsiella pneumoniae virulence factors production was tested. The production of Klebsiella pneumoniae virulence factors such as biofilm formation, urease, proteases, hemolysins, and tolerance to oxidative stress was evaluated phenotypically using sub-inhibitory concentration (1/8 MIC) of metformin, N-acetylcysteine, and secnidazole. For more confirmation, qRT-PCR was used to assess the relative expression level of rmpA, wcaG, fimH-1, mrkD, ureA, and khe genes regulating virulence factors production.
Metformin, N-acetylcysteine, and secnidazole were all found to have a powerful inhibitory effect on the production of virulence factors phenotypically. Our results showed a significant reduction in the expression level of rmpA, wcaG, fimH-1, mrkD, ureA, and khe genes. Furthermore, the tested drugs were investigated in vivo to inform their ability to protect mice against Klebsiella pneumoniae pathogenesis.
Metformin, N-acetylcysteine, and secnidazole inhibited the virulence of Klebsiella pneumoniae. Besides combating resistant Klebsiella pneumoniae, the tested drugs could also serve as an adjuvant to traditional antibiotics.
医院中出现的多药耐药型肺炎克雷伯菌对公共健康构成了严重威胁。肺炎克雷伯菌引起的感染在医疗机构中广泛存在，主要为肺炎、血流感染和重症监护病房中新生儿的感染；因此，有必要用新的策略来对抗这种病原体。针对导致宿主损伤和疾病的毒力因子是抗菌治疗的一个新范例，具有减少耐药性等潜在益处。
测试了二甲双胍、N-乙酰半胱氨酸和塞克硝唑对肺炎克雷伯菌毒力因子产生的影响。使用亚抑菌浓度（1/8 MIC）的二甲双胍、N-乙酰半胱氨酸和塞克硝唑，通过表型评估肺炎克雷伯菌毒力因子（如生物膜形成、脲酶、蛋白酶、溶血素和耐氧化应激）的产生。为了更充分的确认，使用 qRT-PCR 评估了调节毒力因子产生的 rmpA、wcaG、fimH-1、mrkD、ureA 和 khe 基因的相对表达水平。
二甲双胍、N-乙酰半胱氨酸和塞克硝唑均对毒力因子的产生具有强大的抑制作用。我们的结果显示 rmpA、wcaG、fimH-1、mrkD、ureA 和 khe 基因的表达水平显著降低。此外，还在体内研究了测试药物，以了解它们保护小鼠免受肺炎克雷伯菌发病机制的能力。
二甲双胍、N-乙酰半胱氨酸和塞克硝唑抑制了肺炎克雷伯菌的毒力。除了对抗耐药性肺炎克雷伯菌外，这些测试药物还可以作为传统抗生素的辅助药物。
