Dataset Information

6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition.

ABSTRACT: Pseudomonas aeruginosa is a well-known pathogenic bacterium that forms biofilms and produces virulence factors via quorum sensing (QS). Interfering with normal QS interactions between signal molecules and their cognate receptors is a developing strategy for attenuating its virulence. Here we tested the hypothesis that 6-gingerol, a pungent oil of fresh ginger, reduces biofilm formation and virulence by antagonistically binding to P. aeruginosa QS receptors. In silico studies demonstrated molecular binding occurs between 6-gingerol and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Experimentally 6-gingerol reduced biofilm formation, several virulence factors (e.g., exoprotease, rhamnolipid, and pyocyanin), and mice mortality. Further transcriptome analyses demonstrated that 6-gingerol successfully repressed QS-induced genes, specifically those related to the production of virulence factors. These results strongly support our hypothesis and offer insight into the molecular mechanism that caused QS gene repression.

SUBMITTER: Kim HS

PROVIDER: S-EPMC4345325 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition.

Kim Han-Shin HS Lee Sang-Hoon SH Byun Youngjoo Y Park Hee-Deung HD

Scientific reports 20150302

Pseudomonas aeruginosa is a well-known pathogenic bacterium that forms biofilms and produces virulence factors via quorum sensing (QS). Interfering with normal QS interactions between signal molecules and their cognate receptors is a developing strategy for attenuating its virulence. Here we tested the hypothesis that 6-gingerol, a pungent oil of fresh ginger, reduces biofilm formation and virulence by antagonistically binding to P. aeruginosa QS receptors. In silico studies demonstrated molecul ...[more]

PMID: 25728862

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Project description:With the rising development of bacterial resistance the search for new medical treatments beyond conventional antimicrobials has become a key aim of public health research. Possible innovative strategies include the inhibition of bacterial virulence. However, consideration must be given to the evolutionary and environmental consequences of such new interventions. Virulence and cooperative social behaviour of the bacterium Pseudomonas aeruginosa rely on the quorum-sensing (QS) controlled production of extracellular products (public goods). Hence QS is an attractive target for anti-virulence interventions. During colonization, non-cooperating (and hence less virulent) P. aeruginosa QS-mutants, benefiting from public goods provided by wild type isolates, naturally increase in frequency providing a relative protection from invasive infection. We hypothesized that inhibition of QS-mediated gene expression removes this growth advantage and selection of less virulent QS-mutants, and maintains the predominance of more virulent QS-wild type bacteria. We addressed this possibility in a placebo-controlled trial investigating the anti-QS properties of azithromycin, a macrolide antibiotic devoid of bactericidal activity on P. aeruginosa, but interfering with QS, in intubated patients colonized by P. aeruginosa. In the absence of azithromycin, non-cooperating (and hence less virulent) lasR (QS)-mutants increased in frequency over time. Azithromycin significantly reduced QS-gene expression measured directly in tracheal aspirates. Concomitantly the advantage of lasR-mutants was lost and virulent wild-type isolates predominated during azithromycin treatment. We confirmed these results in vitro with fitness and invasion experiments. Azithromycin reduced growth rate of the wild-type, but not of the lasR-mutant. Furthermore, the lasR-mutant efficiently invaded wild-type populations in the absence, but not in the presence of azithromycin. These in vivo and in vitro results demonstrate that anti-virulence interventions based on QS-blockade diminish natural selection towards reduced virulence and therefore may increase the prevalence of more virulent genotypes in the Hospital environment. More generally, the impact of intervention on the evolution of virulence of pathogenic bacteria should be assessed.

Dataset Information

6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition.

Publications

6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition.

Similar Datasets

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