Arami Negin, Tajani Amineh Sadat, Hashemi Maryam, Rezaei Tahoura, Ghodsi Razieh, Soheili Vahid, Bazzaz Bibi Sedigheh Fazly
Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Mol Biol Rep. 2025 Jan 30;52(1):175. doi: 10.1007/s11033-025-10270-3.
Pseudomonas aeruginosa's inherent and adapted resistance makes this pathogen a serious problem for antimicrobial treatments. Furthermore, its biofilm formation ability is the most critical armor against antimicrobial therapy, and the virulence factors, on the other hand, contribute to fatal infection and other recalcitrant phenotypic characteristics. These capabilities are harmonized through cell-cell communication called Quorum Sensing (QS), which results in gene expression regulation via three major interconnected circuits: las, rhl, and pqs system. Pqs circuit specificity in P. aeruginosa made this system an attractive target for antipseudomonal therapy. The current study focuses on novel chalcone derivatives that attenuate P. aeruginosa's pathogenicity by inhibiting the QS system. Chalcones are included in the flavonoid class of phenolic compounds. This family forms one of the greatest groups of bioactive natural products.
The chalcone derivatives's potential activity against the QS system was evaluated through biofilm inhibition, decreased virulence factors production, and gene expression.
Among all the tested compounds, 5H and NMe chalcone derivatives reduced biofilm formation by 60.9% and 78.9%, respectively, and virulence factors production, including pyocyanin (decreased by 5H 30.9% and NMe2 30.7%) and pyoverdine (decreased by 5H 47.1% and NMe2 56.9%) and the QS gene expression (LasR, RhlR, and PqsR) more effectively than other derivatives.
These chalcone compounds can be used as a supplement besides antimicrobial chemotherapy to attenuate pseudomonas pathogenicity.
铜绿假单胞菌的固有耐药性和适应性耐药使其成为抗菌治疗中的一个严重问题。此外，其生物膜形成能力是对抗菌治疗最关键的防护，而毒力因子则导致致命感染和其他顽固的表型特征。这些能力通过称为群体感应（QS）的细胞间通讯得以协调，这导致通过三个主要相互连接的回路对基因表达进行调控：las、rhl和pqs系统。铜绿假单胞菌中pqs回路的特异性使该系统成为抗铜绿假单胞菌治疗的一个有吸引力的靶点。当前的研究聚焦于通过抑制QS系统来减弱铜绿假单胞菌致病性的新型查尔酮衍生物。查尔酮属于酚类化合物中的黄酮类。这个家族构成了最大的生物活性天然产物群体之一。
通过生物膜抑制、毒力因子产生减少和基因表达来评估查尔酮衍生物对QS系统的潜在活性。
在所有测试的化合物中，5H和NMe查尔酮衍生物分别使生物膜形成减少了60.9%和78.9%，并比其他衍生物更有效地减少了毒力因子的产生，包括绿脓菌素（5H减少30.9%，NMe2减少30.7%）和绿脓杆菌素（5H减少47.1%，NMe2减少56.9%）以及QS基因表达（LasR、RhlR和PqsR）。
这些查尔酮化合物除抗菌化疗外可作为一种补充剂来减弱假单胞菌的致病性。
