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Sodium New Houttuyfonate Affects Transcriptome and Virulence Factors of Pseudomonas aeruginosa Controlled by Quorum Sensing.

ABSTRACT: As a major opportunistic pathogen, Pseudomonas aeruginosa can produce various virulence factors and form biofilms. These processes are controlled by the quorum sensing (QS) system. Sodium new houttuyfonate (SNH) is an adduct of houttuyfonate, the main component of the common Chinese medicine plant Houttuynia cordata, which has antibacterial and anti-inflammatory effects. We evaluated the effect of SNH on P. aeruginosa biofilms, virulence factors, and transcription. Transcriptome analysis showed that the key rhlI and pqsA genes of the P. aeruginosa QS system were down-regulated after SNH treatment. SNH reduces proteases and pyocyanin production and inhibits biofilm formation by regulating the P. aeruginosa QS system. SNH also changes the expression of genes related to virulence factors and biofilms (lasA, lasB, lecA, phzM, pqsA, and pilG). These results suggested that the mechanism of SNH against P. aeruginosa by affecting the expression of biofilm and virulence factors controlled by quorum sensing.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC7566558 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Sodium New Houttuyfonate Affects Transcriptome and Virulence Factors of Pseudomonas aeruginosa Controlled by Quorum Sensing.

Zhao Yeye Y Mei Longfei L Si Yuanqing Y Wu Jiadi J Shao Jing J Wang Tianming T Yan Guiming G Wang Changzhong C Wu Daqiang D

Frontiers in pharmacology 20201002

As a major opportunistic pathogen, Pseudomonas aeruginosa can produce various virulence factors and form biofilms. These processes are controlled by the quorum sensing (QS) system. Sodium new houttuyfonate (SNH) is an adduct of houttuyfonate, the main component of the common Chinese medicine plant Houttuynia cordata, which has antibacterial and anti-inflammatory effects. We evaluated the effect of SNH on P. aeruginosa biofilms, virulence factors, and transcription. Transcriptome an ...[more]

PMID: 33123010

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Project description:In the opportunistic pathogen Pseudomonas aeruginosa, quorum sensing (QS) via acyl-homoserine lactone (AHL) signals coordinates virulence gene expression. AHL signals must reach a critical threshold before enough is bound by cognate regulators LasR and RhlR to drive transcription of target genes. In addition, three anti-activator proteins, QteE, QscR, and QslA, sequester QS regulators to increase the threshold for induction and delay expression of QS target genes. It remains unclear how multiple anti-activators work together to achieve the quorum threshold. Here, we employed a combination of mutational, kinetic, phenotypic, and transcriptomic analysis to examine regulatory effects and interactions of the three distinct anti-activators. We observed combinatorial, additive effects on QS gene expression. As measured by reporter gene fusion, individual deletion of each anti-activator gene increased lasB expression and QS-controlled virulence factor production. Deletion of qslA in combination with the deletion of any other anti-activator gene resulted in the greatest increase and earliest activation of lasB gene expression. Western analysis revealed that relative increases in soluble LasR in anti-activator mutants correlate with increased lasB expression and QS-controlled virulence factor production. RNA-seq of the previously uncharacterized QslA and QteE regulons revealed overlapping, yet distinct groups of differentially expressed genes. Simultaneous inactivation of qteE and qslA had the largest effect on gene expression with 999 genes induced and 798 genes repressed in the double mutant vs. wild-type. We found that LasR and RhlR-activated QS genes formed a subset of the genes induced in the qteE, qslA, and double mutant. The activation of almost all of these QS genes was advanced from stationary phase to log phase in the qteE qslA double mutant. Taken together, our results identify additive effects of anti-activation on QS gene expression, likely via LasR and RhlR, but do not rule out QS-independent effects.

Dataset Information

Sodium New Houttuyfonate Affects Transcriptome and Virulence Factors of Pseudomonas aeruginosa Controlled by Quorum Sensing.

Publications

Sodium New Houttuyfonate Affects Transcriptome and Virulence Factors of <i>Pseudomonas aeruginosa</i> Controlled by Quorum Sensing.

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