State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, China.
Microb Biotechnol. 2021 Mar;14(2):677-691. doi: 10.1111/1751-7915.13729. Epub 2020 Dec 30.
Diallyl sulfide (DAS) and diallyl disulfide (DADS), two constituents of garlic, can inhibit quorum sensing (QS) systems of Pseudomonas aeruginosa. However, the differences in the mechanism of QS inhibition between DAS and DADS, and the functional chemical groups of these sulfides that contribute in QS inhibition have not been elucidated yet. We assumed that the sulfide group might play a key role in QS inhibition. To prove this hypothesis and to clarify these unsolved problems, in this study, we synthesized diallyl ether (DAE), and compared and investigated the effects of DAS and DAE on the growth and production of virulence factors, including Pseudomonas quinolone signal (PQS), elastase and pyocyanin, of P. aeruginosa PAO1. Transcriptome analysis and qRT-PCR were used to compare and analyse the differentially expressed genes between the different treatment groups (DAS, DAE and control). The results indicated that DAS did not affect the growth dynamics of P. aeruginosa PAO1; however, DAS inhibited transcription of most of the QS system genes, including lasR, rhlI/rhlR and pqsABCDE/pqsR; thus, biosynthesis of the signal molecules C -HSL (encoded by rhlI) and PQS (encoded by pqsABCDE) was inhibited. Furthermore, DAS inhibited the transcription of virulence genes regulated by the QS systems, including rhlABC, lasA, lasB, lecA and phzAB, phzDEFG, phzM and phzS that encode for rhamnolipid, exoprotease, elastase, lectin and pyocyanin biosynthesis respectively. DAS also enhanced the expression of the key genes involved in the biosynthesis of three B vitamins: folate, thiamine and riboflavin. In conclusion, DAS suppressed the production of some virulence factors toxic to the host and enhanced the production of some nutrition factors beneficial to the host. These actions of DAS may be due to its thioether group. These findings would be significant for development of an effective drug to control the virulence and pathogenesis of the opportunistic pathogen P. aeruginosa.
二烯丙基二硫醚（DAS）和二烯丙基三硫醚（DADS）是大蒜的两种成分，可抑制铜绿假单胞菌的群体感应（QS）系统。然而，DAS 和 DADS 抑制 QS 系统的机制以及这些硫化物中参与 QS 抑制的功能化学基团尚未阐明。我们假设硫醚基团可能在 QS 抑制中发挥关键作用。为了证明这一假设并阐明这些未解决的问题，在这项研究中，我们合成了二烯丙基醚（DAE），并比较和研究了 DAS 和 DAE 对铜绿假单胞菌 PAO1 的生长和毒力因子（包括绿脓菌素信号（PQS）、弹性蛋白酶和吡咯喹啉）产生的影响。通过转录组分析和 qRT-PCR 比较和分析了不同处理组（DAS、DAE 和对照组）之间差异表达的基因。结果表明，DAS 不影响铜绿假单胞菌 PAO1 的生长动态；然而，DAS 抑制了大多数 QS 系统基因的转录，包括 lasR、rhlI/rhlR 和 pqsABCDE/pqsR；因此，信号分子 C-HSL（由 rhlI 编码）和 PQS（由 pqsABCDE 编码）的生物合成受到抑制。此外，DAS 抑制了受 QS 系统调控的毒力基因的转录，包括编码 rhamnolipid、外蛋白酶、弹性蛋白酶、凝集素和吡咯喹啉生物合成的 rhlABC、lasA、lasB、lecA 和 phzAB、phzDEFG、phzM 和 phzS 基因。DAS 还增强了参与三种 B 族维生素（叶酸、硫胺素和核黄素）生物合成的关键基因的表达。总之，DAS 抑制了一些对宿主有毒的毒力因子的产生，并增强了一些对宿主有益的营养因子的产生。DAS 的这些作用可能归因于其硫醚基团。这些发现对于开发有效药物控制机会性病原体铜绿假单胞菌的毒力和发病机制具有重要意义。
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