Inhibition of Pseudomonas aeruginosa Swarming Motility by 1-Naphthol and Other Bicyclic Compounds Bearing Hydroxyl Groups
Inhibition of Pseudomonas aeruginosa Swarming Motility by 1-Naphthol and Other Bicyclic Compounds Bearing Hydroxyl Groups
复制标题
DOI：
10.1128/aem.04220-14
复制
发表时间：
2015-04-01
影响因子：
4.4
通讯作者：
Nomura, Nobuhiko
中科院分区：
文献类型：
--
作者：
Oura, Hiromu;Tashiro, Yosuke;Nomura, Nobuhiko
许多细菌将双环化合物，如吲哚和萘，转化为氧化化合物，包括羟基吲哚和萘酚。铜绿假单胞菌是一种普遍存在的细菌，栖息在不同的环境中，对动物、植物和其他微生物显示出致病性，越来越多的证据表明，几种双环化合物改变了铜绿假单胞菌的毒力相关表型。在这里，我们发现，羟基吲哚（4-和5-羟基吲哚）和萘衍生物轴承羟基特异性抑制群集运动，但对其他运动，包括游泳和抽搐，在铜绿假单胞菌的影响很小。使用1-萘酚的进一步分析表明，这种作用也与临床分离的超温铜绿假单胞菌细胞有关。群集运动性与细胞从生物膜的分散有关，并且1-萘酚的加入维持生物膜生物量而没有细胞分散。我们发现，这种1-萘酚依赖性群集抑制是独立的变化的鼠李糖脂生产和细胞内水平的信号分子环二-GMP（c-di-GMP）。转录组分析显示，1-萘酚增加与多药外排相关的基因表达，并抑制与嗜氧性和绿脓菌螯铁蛋白，鞭毛和菌毛合成相关的基因表达。在本研究中，我们发现了几种带有羟基的双环化合物抑制铜绿假单胞菌的群集运动，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。
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.