Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafr El Sheikh University, Kafr El Sheikh, 33516, Egypt.
Curr Microbiol. 2020 Jun;77(6):1051-1060. doi: 10.1007/s00284-020-01909-4. Epub 2020 Feb 4.
Pseudomonas aeruginosa coordinates the secretion of virulence factors through quorum sensing. Quorum sensing inhibitors can attenuate the pathogenesis of bacteria and help the immune system to eradicate them without targeting the bacterial growth. This study aimed to explore the anti-quorum sensing and anti-virulence activities of sitagliptin against P. aeruginosa PAO1 strain. Sub-inhibitory concentration of sitagliptin significantly inhibited the virulence factors pyocyanin, hemolysin, protease and elastase in addition to blocking swimming, swarming and twitching motilities and biofilm formation. In silico analysis showed that sitagliptin interacted with LasR receptors by hydrogen bonding and hydrophobic interaction, mainly with the amino acids leucine present at positions 40 and 125, tyrosine at position 56, serine at position 129, tryptophan at position 60, alanine at position 50 and phenyl alanine at position 101. qRT-PCR confirmed the anti-quorum sensing activity by reducing the expression level of QS genes lasI, lasR, rhlI, rhlR, pqsA and pqsR. In conclusion, sitagliptin is a novel anti-quorum sensing agent that can be used for treating P. aeruginosa infections.
铜绿假单胞菌通过群体感应协调毒力因子的分泌。群体感应抑制剂可以减弱细菌的发病机制，帮助免疫系统在不针对细菌生长的情况下消灭它们。本研究旨在探索西他列汀对铜绿假单胞菌 PAO1 株的抗群体感应和抗毒力活性。亚抑制浓度的西他列汀显著抑制了包括绿脓菌素、溶血素、蛋白酶和弹性蛋白酶在内的毒力因子，同时还阻止了游泳、群集和扭动运动以及生物膜形成。计算机分析表明，西他列汀通过氢键和疏水相互作用与 LasR 受体相互作用，主要与位于位置 40 和 125 的亮氨酸、位置 56 的酪氨酸、位置 129 的丝氨酸、位置 60 的色氨酸、位置 50 的丙氨酸和位置 101 的苯丙氨酸相互作用。qRT-PCR 证实了通过降低 QS 基因 lasI、lasR、rhlI、rhlR、pqsA 和 pqsR 的表达水平来实现抗群体感应活性。总之，西他列汀是一种新型的抗群体感应剂，可用于治疗铜绿假单胞菌感染。
