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2-Hydroxymethyl-1-methyl-5-nitroimidazole, one siderophore inhibitor, occludes quorum sensing in Pseudomonas aeruginosa
Frontiers in Cellular and Infection Microbiology ( IF 4.6 ) Pub Date : 2022-09-08 , DOI: 10.3389/fcimb.2022.955952
Lujun Yin 1 , Wang Shen 1 , Jun-Sheng Liu 1 , Ai-Qun Jia 1, 2
Affiliation  

Siderophore is necessary for the survival of microorganisms and is interregulated with quorum sensing (QS) systems. It is related to growth, proliferation, virulence, and other bacterial social activities as a virulence factor. Thus, we speculated that the QS system could be occluded by inhibiting siderophore production. 2-Hydroxymethyl-1-methyl-5-nitroimidazole (HMMN), one siderophore inhibitor of Pseudomonas aeruginosa PAO1 (P. aeruginosa PAO1), was obtained by using the Chromeazurol S (CAS) method. We found that HMMN inhibited siderophore production and influenced the biological effects of QS regulation, including biofilm formation and pyocyanin production. HMMN (150 μg/ml) inhibited the siderophore production of P. aeruginosa PAO1 by 69.37%. In addition, HMMN could inhibit pyocyanin production and biofilm formation and erase the formed biofilm of P. aeruginosa PAO1. HMMN (150 μg/ml) inhibited the biofilm formation of P. aeruginosa PAO1 by 28.24%. The erasure rate of the formed biofilm reached 17.03%. Furthermore, HMMN (150 μg/ml) inhibited P. aeruginosa PAO1 pyocyanin production by 36.06%. Meanwhile, positive-control hordenine (500.0 μg/ml) reduced the biofilm formation and pyocyanin production of P. aeruginosa PAO1 by 14.42% and 34.35%, respectively. The erasure rate of hordenine to the formed biofilm is 11.05% at 500 μg/ml. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that HMMN downregulates not only siderophore-related genes but also QS-related genes, as well as hordenine. These results suggest that a siderophore inhibitor could be used as a QS inhibitor to occlude the QS system and reduce virulence.



中文翻译:

2-Hydroxymethyl-1-methyl-5-nitroimidazole,一种铁载体抑制剂,阻断铜绿假单胞菌的群体感应

铁载体是微生物生存所必需的,并与群体感应 (QS) 系统相互调节。它作为一种毒力因子与生长、增殖、毒力和其他细菌社会活动有关。因此,我们推测 QS 系统可以通过抑制铁载体的产生而被封闭。2-Hydroxymethyl-1-methyl-5-nitroimidazole (HMMN),一种铁载体抑制剂铜绿假单胞菌PAO1 (铜绿假单胞菌PAO1),通过使用 Chromeazurol S (CAS) 方法获得。我们发现 HMMN 抑制铁载体的产生并影响 QS 调节的生物学效应,包括生物膜的形成和绿脓素的产生。HMMN (150 μg/ml) 抑制铁载体的产生铜绿假单胞菌PAO1 下降 69.37%。此外,HMMN可以抑制绿脓素的产生和生物膜的形成,并消除已形成的生物膜。铜绿假单胞菌PAO1。HMMN (150 μg/ml) 抑制生物膜的形成铜绿假单胞菌PAO1 增加 28.24%。形成的生物膜的擦除率达到17.03%。此外,HMMN (150 μg/ml) 抑制铜绿假单胞菌PAO1 绿脓素产量增加 36.06%。同时,阳性对照大麦(500.0 μg/ml)减少了生物膜的形成和绿脓素的产生。铜绿假单胞菌PAO1 分别增加了 14.42% 和 34.35%。在 500 μg/ml 时,大麦对形成的生物膜的擦除率为 11.05%。定量实时聚合酶链反应 (qRT-PCR) 表明,HMMN 不仅下调铁载体相关基因,还下调 QS 相关基因以及大麦碱。这些结果表明铁载体抑制剂可用作QS抑制剂以封闭QS系统并降低毒力。

更新日期:2022-09-08
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