Nazik Hasan, Sass Gabriele, Williams Paul, Déziel Eric, Stevens David A
Infectious Diseases Research Laboratory, California Institute for Medical Research, San Jose, CA 95128, USA.
Biodiscovery Institute and School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
J Fungi (Basel). 2021 Apr 28;7(5):343. doi: 10.3390/jof7050343.
The Pseudomonas quinolone signal (PQS) is an important quorum-sensing molecule for that regulates virulence factors, chelates iron, and is an important factor in interactions with eukaryotes, including fungi and mammalian hosts. It was previously shown to inhibit or boost , depending on the milieu iron concentration. We studied several molecular modifications of the PQS molecule, and their effects on biofilm metabolism and growth in vitro, and the effects of iron supplementation. We found that most molecules inhibited at concentrations similar to that of PQS, but with relatively flat dose-responses, and all were less potent than PQS. The inhibition was reversible by iron, suggesting interference with fungal iron metabolism. Stimulation of was not noted. We conclude that the critical -inhibiting moeities of the PQS molecule were partially, but not completely, interfered with by molecular modifications at several sites on the PQS molecule. The mechanism, as with PQS, appears to relate to fungal iron metabolism.
铜绿假单胞菌喹诺酮信号(PQS)是一种重要的群体感应分子,可调节毒力因子、螯合铁,并且是与包括真菌和哺乳动物宿主在内的真核生物相互作用的重要因素。先前已表明,根据环境铁浓度,它可抑制或促进[具体内容缺失]。我们研究了PQS分子的几种分子修饰及其对[具体内容缺失]生物膜代谢和体外生长的影响,以及铁补充的影响。我们发现,大多数分子在与PQS相似的浓度下抑制[具体内容缺失],但剂量反应相对平缓,并且所有分子的效力均低于PQS。这种抑制作用可被铁逆转,表明其干扰了真菌的铁代谢。未观察到对[具体内容缺失]的刺激作用。我们得出结论,PQS分子的关键[具体内容缺失]抑制部分被PQS分子上几个位点的分子修饰部分但未完全干扰。与PQS一样,其机制似乎与真菌铁代谢有关。