期刊
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
卷 85, 期 8, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AEM.00105-19
关键词
AHL; BDSF; Burkholderia cenocepacia; quorum sensing; virulence
资金
- Guangdong Natural Science Funds for Distinguished Young Scholars [2014A030306015]
- National Key Project for Basic Research of China [2015CB150600]
- National Natural Science Foundation of China [31571969]
Quorum sensing (QS) signals are widely used by bacterial pathogens to control biological functions and virulence in response to changes in cell population densities. Burkholderia cenocepacia employs a molecular mechanism in which the cis-2-dodecenoic acid (named Burkholderia diffusible signal factor [BDSF]) QS system regulates N-acyl homoserine lactone (AHL) signal production and virulence by modulating intracellular levels of cyclic diguanosine monophosphate (c-di-GMP). Thus, inhibition of BDSF signaling may offer a non-antibiotic-based therapeutic strategy against BDSF-regulated bacterial infections. In this study, we report the synthesis of small-molecule mimics of the BDSF signal and evaluate their ability to inhibit BDSF QS signaling in B. cenocepacia. A novel structural analogue of BDSF, 14-Me-C-16:Delta(2)(cis-14-methylpentadec-2-enoic acid), was observed to inhibit BDSF production and impair BDSF-regulated phenotypes in B. cenocepacia, including motility, biofilm formation, and virulence, while it did not inhibit the growth rate of this pathogen. 14-Me-C-16:Delta(2) also reduced AHL signal production. Genetic and biochemical analyses showed that 14-Me-C-16:Delta(2) inhibited the production of the BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Notably, 14-Me-C-16:Delta(2) attenuated BDSF-regulated phenotypes in various Burkholderia species. These findings suggest that 14-Me-C-16:Delta(2) could potentially be developed as a new therapeutic agent against pathogenic Burkholderia species by interfering with their QS signaling. IMPORTANCE Burkholderia cenocepacia is an important opportunistic pathogen which can cause life-threatening infections in susceptible individuals, particularly in cystic fibrosis and immunocompromised patients. It usually employs two types of quorum sensing (QS) systems, including the cis-2-dodecenoic acid (BDSF) system and N-acyl homoserine lactone (AHL) system, to regulate virulence. In this study, we have designed and identified an unsaturated fatty acid compound (cis-14-methylpentadec-2-enoic acid [14-Me-C-16:Delta 2]) that is capable of interfering with B. cenocepacia QS signaling and virulence. We demonstrate that 14-Me-C-16:Delta 2 reduced BDSF and AHL signal production in B. cenocepacia. It also impaired QS-regulated phenotypes in various Burkholderia species. These results suggest that 14-Me-C-16:Delta 2 could interfere with QS signaling in many Burkholderia species and might be developed as a new antibacterial agent.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据