Oura Hiromu, Tashiro Yosuke, Toyofuku Masanori, Ueda Kousetsu, Kiyokawa Tatsunori, Ito Satoshi, Takahashi Yurika, Lee Seunguk, Nojiri Hideaki, Nakajima-Kambe Toshiaki, Uchiyama Hiroo, Futamata Hiroyuki, Nomura Nobuhiko
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Department of Applied Chemistry and Biochemical Engineering, Graduate School of Engineering, Shizuoka University, Hamamatsu, Shizuoka, Japan.
Appl Environ Microbiol. 2015 Apr;81(8):2808-18. doi: 10.1128/AEM.04220-14. Epub 2015 Feb 13.
Many bacteria convert bicyclic compounds, such as indole and naphthalene, to oxidized compounds, including hydroxyindoles and naphthols. Pseudomonas aeruginosa, a ubiquitous bacterium that inhabits diverse environments, shows pathogenicity against animals, plants, and other microorganisms, and increasing evidence has shown that several bicyclic compounds alter the virulence-related phenotypes of P. aeruginosa. Here, we revealed that hydroxyindoles (4- and 5-hydroxyindoles) and naphthalene derivatives bearing hydroxyl groups specifically inhibit swarming motility but have minor effects on other motilities, including swimming and twitching, in P. aeruginosa. Further analyses using 1-naphthol showed that this effect is also associated with clinically isolated hyperswarming P. aeruginosa cells. Swarming motility is associated with the dispersion of cells from biofilms, and the addition of 1-naphthol maintained biofilm biomass without cell dispersion. We showed that this 1-naphthol-dependent swarming inhibition is independent of changes of rhamnolipid production and the intracellular level of signaling molecule cyclic-di-GMP (c-di-GMP). Transcriptome analyses revealed that 1-naphthol increases gene expression associated with multidrug efflux and represses gene expression associated with aerotaxis and with pyochelin, flagellar, and pilus synthesis. In the present study, we showed that several bicyclic compounds bearing hydroxyl groups inhibit the swarming motility of P. aeruginosa, and these results provide new insight into the chemical structures that inhibit the specific phenotypes of P. aeruginosa.
许多细菌能将双环化合物,如吲哚和萘,转化为氧化产物,包括羟基吲哚和萘酚。铜绿假单胞菌是一种广泛存在于各种环境中的细菌,对动物、植物和其他微生物具有致病性,越来越多的证据表明,几种双环化合物会改变铜绿假单胞菌的毒力相关表型。在此,我们发现羟基吲哚(4-羟基吲哚和5-羟基吲哚)以及带有羟基的萘衍生物能特异性抑制铜绿假单胞菌的群体运动,但对其他运动,包括游泳运动和震颤运动的影响较小。使用1-萘酚的进一步分析表明,这种效应也与临床分离的超群体运动型铜绿假单胞菌细胞有关。群体运动与生物膜中细胞的分散有关,添加1-萘酚可维持生物膜生物量而不导致细胞分散。我们表明,这种依赖1-萘酚的群体运动抑制与鼠李糖脂产量的变化以及信号分子环二鸟苷(c-di-GMP)的细胞内水平无关。转录组分析显示,1-萘酚增加了与多药外排相关的基因表达,并抑制了与趋氧性以及绿脓菌素、鞭毛和菌毛合成相关的基因表达。在本研究中,我们表明几种带有羟基的双环化合物可抑制铜绿假单胞菌的群体运动,这些结果为抑制铜绿假单胞菌特定表型的化学结构提供了新的见解。