Indole and 7-benzyloxyindole attenuate the virulence of Staphylococcus aureus
Indole and 7-benzyloxyindole attenuate the virulence of Staphylococcus aureus
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DOI：
10.1007/s00253-012-4674-z
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发表时间：
2013-05-01
影响因子：
5
通讯作者：
Lee, Jintae
中科院分区：
文献类型：
--
作者：
Lee, Jin-Hyung;Cho, Hyun Seob;Lee, Jintae
由于长期使用主要抑制细菌生长的抗生素，人类病原体很容易产生耐药性。与抗生素不同，抗毒化合物在不影响细胞活力的情况下减少细菌的毒力，因此，可能不会导致耐药性。金黄色葡萄球菌是院内感染的主要病原体，并产生多种毒力因子，如黄色类胡萝卜素葡萄黄质，可促进对活性氧（ROS）和宿主免疫系统的抵抗。为了寻找新的抗毒化合物，研究了动物肠道中存在的细菌信号吲哚和多种吲哚衍生物在减少金黄色葡萄球菌葡萄黄质产生和溶血活性方面的作用。吲哚或其衍生物7-苯氧吲哚（7BOI）使金黄色葡萄球菌变成无色，抑制其溶血能力，但不影响细菌生长。结果表明，在吲哚或7BOI存在的情况下，金黄色葡萄球菌更容易被过氧化氢（H2O2）和人全血杀死。此外，7BOI在一个容易被金黄色葡萄球菌感染和杀死的秀丽隐杆线虫体内模型中降低了金黄色葡萄球菌的毒力。转录分析表明，吲哚和7BOI均抑制了α -溶血素基因hla、肠毒素seb、蛋白酶基因splA和sspA等毒力基因的表达，并调节了重要的调控基因agrA和sarA的表达。这些发现表明吲哚衍生物是潜在的候选物，用于抗持久性金黄色葡萄球菌感染的抗毒策略。
Human pathogens can readily develop drug resistance due to the long-term use of antibiotics that mostly inhibit bacterial growth. Unlike antibiotics, antivirulence compounds diminish bacterial virulence without affecting cell viability and thus, may not lead to drug resistance. Staphylococcus aureus is a major agent of nosocomial infections and produces diverse virulence factors, such as the yellow carotenoid staphyloxanthin, which promotes resistance to reactive oxygen species (ROS) and the host immune system. To identify novel antivirulence compounds, bacterial signal indole present in animal gut and diverse indole derivatives were investigated with respect to reducing staphyloxanthin production and the hemolytic activity of S. aureus. Treatment with indole or its derivative 7-benzyloxyindole (7BOI) caused S. aureus to become colorless and inhibited its hemolytic ability without affecting bacterial growth. As a result, S. aureus was more easily killed by hydrogen peroxide (H2O2) and by human whole blood in the presence of indole or 7BOI. In addition, 7BOI attenuated S. aureus virulence in an in vivo model of nematode Caenorhabditis elegans, which is readily infected and killed by S. aureus. Transcriptional analyses showed that both indole and 7BOI repressed the expressions of several virulence genes such as alpha-hemolysin gene hla, enterotoxin seb, and the protease genes splA and sspA and modulated the expressions of the important regulatory genes agrA and sarA. These findings show that indole derivatives are potential candidates for use in antivirulence strategies against persistent S. aureus infection.