Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA.
Microb Biotechnol. 2009 Jan;2(1):75-90. doi: 10.1111/j.1751-7915.2008.00061.x. Epub 2008 Oct 14.
Indole is an extracellular biofilm signal for Escherichia coli, and many bacterial oxygenases readily convert indole to various oxidized compounds including 7-hydroxyindole (7HI). Here we investigate the impact of indole and 7HI on Pseudomonas aeruginosa PAO1 virulence and quorum sensing (QS)-regulated phenotypes; this strain does not synthesize these compounds but degrades them rapidly. Indole and 7HI both altered extensively gene expression in a manner opposite that of acylhomoserine lactones; the most repressed genes encode the mexGHI-opmD multidrug efflux pump and genes involved in the synthesis of QS-regulated virulence factors including pyocyanin (phz operon), 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) signal (pqs operon), pyochelin (pch operon) and pyoverdine (pvd operon). Corroborating these microarray results, indole and 7HI decreased production of pyocyanin, rhamnolipid, PQS and pyoverdine and enhanced antibiotic resistance. In addition, indole affected the utilization of carbon, nitrogen and phosphorus, and 7HI abolished swarming motility. Furthermore, 7HI reduced pulmonary colonization of P. aeruginosa in guinea pigs and increased clearance in lungs. Hence, indole-related compounds have potential as a novel antivirulence approach for the recalcitrant pathogen P. aeruginosa.
吲哚是大肠杆菌的一种细胞外生物膜信号分子，许多细菌加氧酶容易将吲哚转化为各种氧化化合物，包括 7-羟基吲哚（7HI）。在这里，我们研究了吲哚和 7HI 对铜绿假单胞菌 PAO1 毒力和群体感应（QS）调节表型的影响；该菌株本身不能合成这些化合物，但能迅速将其降解。吲哚和 7HI 都以与酰高丝氨酸内酯相反的方式广泛改变基因表达；受抑制最严重的基因编码 mexGHI-opmD 多药外排泵以及与 QS 调节毒力因子合成有关的基因，包括绿脓菌素（phz 操纵子）、2-庚基-3-羟基-4(1H)-喹啉（PQS）信号（pqs 操纵子）、吡咯烷酮（pch 操纵子）和吡咯烷（pvd 操纵子）。这些微阵列结果得到了证实，吲哚和 7HI 降低了绿脓菌素、鼠李糖脂、PQS 和吡咯烷的产生，并增强了抗生素抗性。此外，吲哚还影响碳、氮和磷的利用，而 7HI 则消除了群体运动性。此外，7HI 减少了豚鼠肺部铜绿假单胞菌的定植，并增加了肺部的清除率。因此，吲哚相关化合物有可能成为一种针对铜绿假单胞菌这种顽固病原体的新型抗毒力方法。
