毒力
绿脓素
铜绿假单胞菌
群体感应
微生物学
分泌物
生物膜
群集运动
三型分泌系统
紫红色杆菌
生物
细菌
效应器
毒力因子
致病菌
假单胞菌
生物化学
基因
遗传学
作者
Naybi Muñoz‐Cazares,Israel Castillo‐Juárez,Rodolfo García‐Contreras,Víctor Alberto Castro-Torres,Miguel Díaz-Guerrero,José S. Rodríguez‐Zavala,Héctor Quezada,Bertha González‐Pedrajo,Mariano Martínez‐Vázquez
出处
期刊:Biomedicines
[MDPI AG]
日期:2022-07-31
卷期号:10 (8): 1847-1847
被引量:3
标识
DOI:10.3390/biomedicines10081847
摘要
Quorum sensing (QS) and type III secretion systems (T3SSs) are among the most attractive anti-virulence targets for combating multidrug-resistant pathogenic bacteria. Some halogenated furanones reduce QS-associated virulence, but their role in T3SS inhibition remains unclear. This study aimed to assess the inhibition of these two systems on Pseudomonas aeruginosa virulence. The halogenated furanones (Z)-4-bromo-5-(bromomethylene)-2(5H) (C-30) and 5-(dibromomethylene)-2(5H) (named hereafter GBr) were synthesized, and their ability to inhibit the secretion of type III exoenzymes and QS-controlled virulence factors was analyzed in P. aeruginosa PA14 and two clinical isolates. Furthermore, their ability to prevent bacterial establishment was determined in a murine cutaneous abscess model. The GBr furanone reduced pyocyanin production, biofilm formation, and swarming motility in the same manner or more effectively than C-30. Moreover, both furanones inhibited the secretion of ExoS, ExoT, or ExoU effectors in all tested strains. The administration of GBr (25 and 50 µM) to CD1 mice infected with the PA14 strain significantly decreased necrosis formation in the inoculation zone and the systemic spread of bacteria more efficiently than C-30 (50 µM). Molecular docking analysis suggested that the gem position of bromine in GBr increases its affinity for the active site of the QS LasR regulator. Overall, our findings showed that the GBr furanone displayed efficient multi-target properties that may favor the development of more effective anti-virulence therapies.
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