Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics.
Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics.
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含色氨酸的抗菌肽会损害多重耐药铜绿假单胞菌的群体感应和生物膜发育，并与抗生素表现出协同作用
DOI：
10.3389/fmicb.2021.611009
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发表时间：
2021
影响因子：
5.2
通讯作者：
Jiang F
中科院分区：
文献类型：
--
作者：
Shang D;Han X;Du W;Kou Z;Jiang F
铜绿假单胞菌使用群体感应(QS)来控制毒力、生物被膜的形成和抗生素外排泵的表达。针对QS系统和生物膜形成的有效小分子的开发代表了一种新的有吸引力的策略。本研究探讨了一系列含Trp的多肽对多重耐药铜绿假单胞菌QS调控的毒力和生物膜发育的影响，以及它们与三类传统化学抗生素的协同抗菌活性。结果表明，低浓度的色氨酸多肽通过下调菌株MRPA0108中LAS和RHL系统的基因表达，减少了QS调节毒力因子的产生。生物膜的形成受到浓度依赖的抑制，这与通过下调PELA、藻D和PSLA转录而抑制胞外多糖的产生有关。这些变化与假单胞菌毒力因子的胞外产生和集群运动的变化有关。此外，低浓度的色氨酸多肽与抗生素头孢他啶和哌拉西林联合使用提供了协同作用。值得注意的是，L11W和L12W与头孢他啶和哌拉西林的协同作用最强。机制研究表明，含有色氨酸的多肽，特别是L12W，显著降低β-内酰胺酶活性和外排泵基因oprM、mexx和mexA的表达，从而减少抗生素从MRPA0108细胞的外排，从而提高这些抗生素对MRPA0108的抗菌活性。
Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence, biofilm formation and antibiotic efflux pump expression. The development of effective small molecules targeting the QS system and biofilm formation represents a novel attractive strategy. In this present study, the effects of a series of Trp-containing peptides on the QS-regulated virulence and biofilm development of multidrug-resistant P. aeruginosa, as well as their synergistic antibacterial activity with three classes of traditional chemical antibiotics were investigated. The results showed that Trp-containing peptides at low concentrations reduced the production of QS-regulated virulence factors by downregulating the gene expression of both the las and rhl systems in the strain MRPA0108. Biofilm formation was inhibited in a concentration-dependent manner, which was associated with extracellular polysaccharide production inhibition by downregulating pelA, algD, and pslA transcription. These changes correlated with alterations in the extracellular production of pseudomonal virulence factors and swarming motility. In addition, the combination of Trp-containing peptides at low concentration with the antibiotics ceftazidime and piperacillin provided synergistic effects. Notably, L11W and L12W showed the highest synergy with ceftazidime and piperacillin. A mechanistic study demonstrated that the Trp-containing peptides, especially L12W, significantly decreased β-lactamase activity and expression of efflux pump genes OprM, MexX, and MexA, resulting in a reduction in antibiotic efflux from MRPA0108 cells and thus increasing the antibacterial activity of these antibiotics against MRPA0108.
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影响因子：
3.9
作者：
Chernysh S;Gordya N;Tulin D;Yakovlev A
通讯作者：
Yakovlev A
影响因子：
4.9
作者：
den Hollander, JG;Mouton, JW;Verbrugh, HA
通讯作者：
Verbrugh, HA
影响因子：
4.2
作者：
Fothergill JL;Panagea S;Hart CA;Walshaw MJ;Pitt TL;Winstanley C
通讯作者：
Winstanley C
影响因子：
17.1
作者：
de Breij, Anna;Riool, Martijn;Nibbering, Peter H.
通讯作者：
Nibbering, Peter H.
两种色氨酸取代的阳离子抗菌肽与脂质双层的抗菌特性和相互作用
影响因子：
3.3
作者：
Bi, Xiaonan;Wang, Che;Shang, Dejing
通讯作者：
Shang, Dejing