Khayat Maan T, Ibrahim Tarek S, Darwish Khaled M, Khayyat Ahdab N, Alharbi Majed, Khafagy El-Sayed, Ali Mohamed A M, Hegazy Wael A H, Abbas Hisham A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
Microorganisms. 2022 Dec 12;10(12):2455. doi: 10.3390/microorganisms10122455.
Bacteria communicate with each other using quorum sensing (QS) which works in an inducer/receptor manner. QS plays the main role in orchestrating diverse bacterial virulence factors. is one of the most clinically important bacterial pathogens that can cause infection in almost all body tissues. Besides its efficient capability to develop resistance to different antibiotics, acquires a huge arsenal of virulence factors that are controlled mainly by QS. Challenging QS with FDA-approved drugs and natural products was proposed as a promising approach to mitigate bacterial virulence enabling the host immunity to complete the eradication of bacterial infection. The present study aims to evaluate the dipeptidase inhibitor-4 inhibitor hypoglycemic linagliptin anti-QS and anti-virulence activities against in vitro, in vivo, and in silico. The current results revealed the significant ability to diminish the production of protease and pyocyanin, motility, and biofilm formation in . Furthermore, the histopathological examination of liver and kidney tissues of mice injected with linagliptin-treated bacteria showed an obvious reduction of pathogenesis. Linagliptin downregulation to QS-encoding genes, besides the virtual ability to interact with QS receptors, indicates its anti-QS activities. In conclusion, linagliptin is a promising anti-virulence and anti-QS candidate that can be used solely or in combination with traditional antimicrobial agents in the treatment of aggressive infections.
细菌通过群体感应（QS）相互交流，群体感应以诱导物/受体的方式起作用。群体感应在协调多种细菌毒力因子方面起主要作用。[细菌名称]是临床上最重要的细菌病原体之一，几乎可在人体所有组织中引发感染。除了对不同抗生素具有高效的耐药能力外，[细菌名称]还拥有大量主要由群体感应控制的毒力因子。有人提出，使用美国食品药品监督管理局（FDA）批准的药物和天然产物来挑战群体感应，是一种有前景的减轻细菌毒力的方法，可使宿主免疫系统彻底根除细菌感染。本研究旨在评估二肽基肽酶-4抑制剂降糖药利那格列汀在体外、体内和计算机模拟实验中对[细菌名称]的抗群体感应及抗毒力活性。目前的结果显示，利那格列汀具有显著降低[细菌名称]蛋白酶和绿脓菌素的产生、运动性及生物膜形成的能力。此外，对注射了经利那格列汀处理的细菌的小鼠肝脏和肾脏组织进行的组织病理学检查显示，发病机制明显减轻。利那格列汀对群体感应编码基因的下调作用，以及其与群体感应受体相互作用的虚拟能力，表明了其抗群体感应活性。总之，利那格列汀是一种有前景的抗毒力和抗群体感应候选药物，可单独使用或与传统抗菌药物联合用于治疗[细菌名称]的侵袭性感染。
