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细菌毒力的控制:哌唑嗪抗毒力活性对……的评估

Controlling of Bacterial Virulence: Evaluation of Anti-Virulence Activities of Prazosin against .

作者信息

Elfaky Mahmoud A, Thabit Abrar K, Eljaaly Khalid, Zawawi Ayat, Abdelkhalek Ahmed S, Almalki Ahmad J, Ibrahim Tarek S, Hegazy Wael A H

机构信息

Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Centre for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Antibiotics (Basel). 2022 Nov 9;11(11):1585. doi: 10.3390/antibiotics11111585.

Abstract

is a Gram-negative orofecal transmitted pathogen that causes a wide diversity of local and systemic illnesses. utilizes several interplayed systems to regulate its invasion and pathogenesis: namely, quorum sensing (QS) and type three secretion system (T3SS). In addition, could sense the adrenergic hormones in the surroundings that enhance its virulence. The current study aimed to evaluate the ability of α-adrenoreceptor antagonist prazosin to mitigate the virulence of serovar Typhimurium. The prazosin effect on biofilm formation and the expression of , , , and T3SS-type II encoding genes was evaluated. Furthermore, the prazosin intracellular replication inside macrophage and anti-virulence activity was evaluated in vivo against . . The current finding showed a marked prazosin ability to compete on SdiA and QseC and downregulate their encoding genes. Prazosin significantly downregulated the virulence factors encoding genes and diminished the biofilm formation, intracellular replication inside macrophages, and in vivo protected mice. To sum up, prazosin showed significant inhibitory activities against QS, T3SS, and bacterial espionage, which documents its considered anti-virulence activities.

摘要

是一种革兰氏阴性经口粪传播病原体,可引发多种局部和全身性疾病。利用多种相互作用的系统来调节其侵袭和发病机制:即群体感应(QS)和三型分泌系统(T3SS)。此外,能感知周围环境中的肾上腺素能激素,增强其毒力。当前研究旨在评估α-肾上腺素能受体拮抗剂哌唑嗪减轻鼠伤寒血清型毒力的能力。评估了哌唑嗪对生物膜形成以及、、和T3SS-II型编码基因表达的影响。此外,还在体内评估了哌唑嗪在巨噬细胞内的复制情况以及对的抗毒力活性。当前研究结果显示,哌唑嗪具有显著能力与SdiA和QseC竞争并下调其编码基因。哌唑嗪显著下调毒力因子编码基因,减少生物膜形成,降低巨噬细胞内的细胞内复制,并在体内保护小鼠。总之,哌唑嗪对QS、T3SS和细菌间谍活动显示出显著抑制活性,证明了其公认的抗毒力活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f14b/9686722/5bd4f8d81a82/antibiotics-11-01585-g001.jpg

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