Wangkheimayum Jayalaxmi, Banerjee Tuhina, Baishya Somorita, Sharma Swati, Choudhury Manabendra Dutta, Laskar Monjur Ahmed, Bhattacharjee Amitabha
Department of Microbiology, Assam University Silchar, India.
Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Germs. 2024 Jun 30;14(2):136-148. doi: 10.18683/germs.2024.1426. eCollection 2024 Jun.
The rise in antimicrobial resistance among bacterial pathogens is a global concern, and anti-virulence therapy may be an alternative strategy to address the issue. Multidrug resistant (MDR) hypervirulent (HvKp) is known to be associated with healthcare associated infections. These are often challenging to treat and here anti-virulence therapy may be a treatment option. The study of anti-virulence compounds against HvKp by in-silico prediction, in-vitro experiments and in-vivo assay enables to determine which anti-virulence compounds are suitable for an alternative approach MDR HvKp.
Modeling of the proteins, ligand binding and molecular docking were performed targeting different hypervirulence genes viz., , and, by in-silico analysis using different bioinformatics tool and software. Minimum inhibitory concentration (MIC) was determined for six anti-virulence compounds; curcumin, eugenol, reserpine, linoleic acid, ε-anethole, and α-thujone by standard protocol. Quantitative real-time PCR was performed selecting two isolates harboring and genes. larva killing assay was used for in-vivo experiment.
In-silico analysis observed that linoleic acid could be the best fit in comparison with the other compounds. None of the anti-virulence compounds showed any inhibitory activity and upon transcriptional expression analysis of the hypervirulence genes; was marginally increased for both the isolates when linoleic acid exposure was given.
In-vivo study revealed that linoleic acid and reserpine showed anti-virulence activity.
细菌病原体对抗菌药物耐药性的增加是一个全球关注的问题，抗毒力疗法可能是解决这一问题的替代策略。已知多重耐药（MDR）高毒力肺炎克雷伯菌（HvKp）与医院感染相关。这些感染通常难以治疗，而抗毒力疗法可能是一种治疗选择。通过计算机预测、体外实验和体内试验研究针对HvKp的抗毒力化合物，能够确定哪些抗毒力化合物适用于MDR HvKp的替代方法。
使用不同的生物信息学工具和软件，通过计算机分析对不同的高毒力基因，即、和进行蛋白质建模、配体结合和分子对接。按照标准方案测定六种抗毒力化合物（姜黄素、丁香酚、利血平、亚油酸、ε-茴芹脑和α-侧柏酮）的最低抑菌浓度（MIC）。选择携带和基因的两个分离株进行定量实时PCR。幼虫杀伤试验用于体内实验。
计算机分析观察到，与其他化合物相比，亚油酸可能是最合适的。抗毒力化合物均未显示出任何抑制活性，并且在对高毒力基因进行转录表达分析时；给予亚油酸处理后，两个分离株的该基因表达均略有增加。
体内研究表明，亚油酸和利血平具有抗毒力活性。
