Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens.
Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens.
复制标题
DOI：
10.3390/ijms232113088
复制
发表时间：
2022-10-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
细菌对抗生素产生耐药性是一个日益严重的公共卫生问题，随着生物膜的形成，这一问题会变得更加严重。群体感应（QS）协调细菌毒力并控制生物膜的形成。针对细菌毒力是克服抗生素耐药性增加的有前途的方法。在之前的一项详细的计算机研究中，假设阿替洛尔是一种有希望的候选药物，筛选了 22 种 β-肾上腺素受体阻滞剂的抗 QS 活性。本研究旨在评估β-肾上腺素受体阻滞剂阿替洛尔对革兰氏阴性菌粘质沙雷氏菌、铜绿假单胞菌和奇异变形杆菌的抗QS、抗生物膜和抗毒力活性。进行了一项计算机研究，以评估阿替洛尔与粘质沙门氏菌 SmaR QS 受体、铜绿假单胞菌 QscR QS 受体和奇异变形杆菌 MrpH 粘附素的结合亲和力。在体外和体内评价阿替洛尔对测试菌株的抗毒力活性。目前的发现表明阿替洛尔具有与 QS 蛋白竞争的相当大的能力，并显着下调 QS 和毒力编码基因的表达。阿替洛尔显示出显着减少测试的细菌生物膜形成、毒力酶产生和运动性。此外，阿替洛尔显着降低了细菌杀死和保护小鼠的能力。总之，阿替洛尔对粘质沙门氏菌、铜绿假单胞菌和奇异变形杆菌具有潜在的抗 QS 和抗毒力活性，可用作治疗侵袭性细菌感染的佐剂。
The development of bacterial resistance to antibiotics is an increasing public health issue that worsens with the formation of biofilms. Quorum sensing (QS) orchestrates the bacterial virulence and controls the formation of biofilm. Targeting bacterial virulence is promising approach to overcome the resistance increment to antibiotics. In a previous detailed in silico study, the anti-QS activities of twenty-two β-adrenoreceptor blockers were screened supposing atenolol as a promising candidate. The current study aims to evaluate the anti-QS, anti-biofilm and anti-virulence activities of the β-adrenoreceptor blocker atenolol against Gram-negative bacteria Serratia marcescens, Pseudomonas aeruginosa, and Proteus mirabilis. An in silico study was conducted to evaluate the binding affinity of atenolol to S. marcescens SmaR QS receptor, P. aeruginosa QscR QS receptor, and P. mirabilis MrpH adhesin. The atenolol anti-virulence activity was evaluated against the tested strains in vitro and in vivo. The present finding shows considerable ability of atenolol to compete with QS proteins and significantly downregulated the expression of QS- and virulence-encoding genes. Atenolol showed significant reduction in the tested bacterial biofilm formation, virulence enzyme production, and motility. Furthermore, atenolol significantly diminished the bacterial capacity for killing and protected mice. In conclusion, atenolol has potential anti-QS and anti-virulence activities against S. marcescens, P. aeruginosa, and P. mirabilis and can be used as an adjuvant in treatment of aggressive bacterial infections.
登录
查看更多内容
DOI：
10.3390/molecules27030671
发表时间：
2022-01-20
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Almalki AJ;Ibrahim TS;Taher ES;Mohamed MFA;Youns M;Hegazy WAH;Al-Mahmoudy AMM
通讯作者：
Al-Mahmoudy AMM
影响因子：
--
作者：
Diggle, Stephen P.;Matthijs, Sandra;Williams, Paul
通讯作者：
Williams, Paul
影响因子：
6.4
作者：
Abisado RG;Benomar S;Klaus JR;Dandekar AA;Chandler JR
通讯作者：
Chandler JR
影响因子：
4.8
作者：
Bottomley, Matthew J.;Muraglia, Ester;Carfi, Andrea
通讯作者：
Carfi, Andrea
影响因子：
5.2
作者：
García-Contreras R
通讯作者：
García-Contreras R