Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafr El Sheikh, Egypt.
J Appl Microbiol. 2022 Oct;133(4):2182-2197. doi: 10.1111/jam.15609. Epub 2022 May 15.
Quorum sensing (QS) inhibition is a promising strategy to suppress bacterial virulence and control infection caused by Gram-negative and Gram-positive bacteria. This study explores the QS inhibiting activity of the non-steroidal anti-inflammatory drugs (NSAIDs) in Acinetobacter baumannii.
Ketoprofen, piroxicam and indomethacin revealed QS inhibition via elimination of violacein production of the reporter strain Chromobacterium violaceum ATCC 12472 without affecting bacterial growth. The minimal inhibitory concentration (MIC) of ketoprofen, piroxicam and indomethacin was determined against A. baumannii strains ATCC 17978, ATCC 19606, A1, A11 and A27 by the microbroth dilution method. The MICs of ketoprofen against tested isolates were 0.7-6.25 mg ml , piroxicam MICs were 1.25-2.5 mg ml , and indomethacin MICs were 3.12-12.5 mg ml . Those compounds significantly inhibited QS-associated virulence factors such as biofilm formation, and surface motility, as well as, significantly increased bacterial tolerance to oxidative stress without affecting bacterial growth. On the molecular level, the three compounds significantly inhibited the transcription of QS regulatory genes abaI/abaR and biofilm-regulated genes cusD and pgaB. Molecular docking analysis revealed the potent binding affinity of the three compounds with AbaI via hydrogen and/or hydrophobic bonds.
These results indicate that NSAIDs, ketoprofen, piroxicam and indomethacin, could be potential inhibitors of the QS and could suppress the QS-related virulence factors of A. baumannii.
Ketoprofen, piroxicam and indomethacin could provide promising implications and strategies for combating the virulence and pathogenesis of A. baumannii.
群体感应（QS）抑制是抑制革兰氏阴性和革兰氏阳性细菌毒力并控制感染的一种有前途的策略。本研究探讨了非甾体抗炎药（NSAIDs）对鲍曼不动杆菌的 QS 抑制活性。
酮洛芬、吡罗昔康和吲哚美辛通过消除报告菌株荧光假单胞菌 ATCC 12472 的紫质产生来显示 QS 抑制作用，而不影响细菌生长。采用微量稀释法测定酮洛芬、吡罗昔康和吲哚美辛对鲍曼不动杆菌 ATCC 17978、ATCC 19606、A1、A11 和 A27 菌株的最小抑菌浓度（MIC）。酮洛芬对测试分离株的 MIC 为 0.7-6.25mg/ml，吡罗昔康的 MIC 为 1.25-2.5mg/ml，吲哚美辛的 MIC 为 3.12-12.5mg/ml。这些化合物显著抑制了 QS 相关的毒力因子，如生物膜形成和表面运动，并显著提高了细菌对氧化应激的耐受性，而不影响细菌生长。在分子水平上，这三种化合物显著抑制了 QS 调节基因 abaI/abaR 和生物膜调节基因 cusD 和 pgaB 的转录。分子对接分析表明，这三种化合物通过氢键和/或疏水键与 AbaI 具有很强的结合亲和力。
这些结果表明，NSAIDs，酮洛芬、吡罗昔康和吲哚美辛可能是 QS 的潜在抑制剂，并可能抑制鲍曼不动杆菌的 QS 相关毒力因子。
酮洛芬、吡罗昔康和吲哚美辛可能为对抗鲍曼不动杆菌的毒力和发病机制提供有前景的启示和策略。
