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Reducing the virulence of Pseudomonas aeruginosa by using multiple quorum-quenching enzymes.

ABSTRACT: The emergence of multidrug-resistant Pseudomonas aeruginosa in healthcare settings poses a tremendous challenge to traditional antibiotic therapy. Pseudomonas aeruginosa utilizes quorum sensing (QS) to coordinate the production of virulence factors and the formation of drug-resistant biofilms. QS is mediated by signal compounds produced by P. aeruginosa as well as signal molecules produced by other non-pseudomonad bacteria. A potential strategy to prevent bacterial pathogenicity is utilizing enzymes to interfere with QS. Here, we used AidC, a quorum-quenching (QQ) enzyme from Chryseobacterium sp. strain StRB126 that can effectively hydrolyze N-(3-oxododecanoyl) homoserine lactone (3OC12-HSL) and N-butanoyl-homoserine lactone (C4-HSL), the major signal molecules synthesized by P. aeruginosa. The exogenous addition of AidC to P. aeruginosa wild-type strain PAO1 cultures significantly reduced the total protease and elastase activities and the production of pyocyanin. In addition, the application of AidC resulted in thin and sparse biofilm formation. Later, we used a metagenomic-derived QQ enzyme, QQ-2, in combination with AidC to attenuate PAO1 virulence when the presence of a non-pseudomonad signal compound, autoinducer-2, aggravated it. These findings suggest that using a combined antimicrobial approach may lead to a more efficacious therapeutic intervention against P. aeruginosa PAO1 infection, as its behavior is modulated in the presence of intraspecies and interspecies signal compounds.

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In this work, the potential of dual enzymes was investigated to interfere with quorum sensing as a novel concept for reducing the virulence of P. aeruginosa, which is influenced by both intra species and interspecies communication.

SUBMITTER: Khatun MA

PROVIDER: S-EPMC10536470 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Reducing the virulence of Pseudomonas aeruginosa by using multiple quorum-quenching enzymes.

Khatun Mst Afroza MA Hoque Md Anarul MA Koffas Mattheos M Feng Yan Y

Journal of industrial microbiology & biotechnology 20230201 1

The emergence of multidrug-resistant Pseudomonas aeruginosa in healthcare settings poses a tremendous challenge to traditional antibiotic therapy. Pseudomonas aeruginosa utilizes quorum sensing (QS) to coordinate the production of virulence factors and the formation of drug-resistant biofilms. QS is mediated by signal compounds produced by P. aeruginosa as well as signal molecules produced by other non-pseudomonad bacteria. A potential strategy to prevent bacterial pathogenicity is utilizing enz ...[more]

PMID: 37738438

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Project description:Pseudomonas aeruginosa is the predominant pathogen in pulmonary infections associated with cystic fibrosis. Quorum sensing (QS) systems regulate the production of virulence factors and play an important role in the establishment of successful P. aeruginosa infections. Inhibition of the QS system (termed quorum quenching) renders the bacteria avirulent thus serving as an alternative approach in the development of novel antibiotics. Quorum quenching in Gram negative bacteria can be achieved by preventing the accumulation of N-acyl homoserine lactone (AHL) signaling molecule via enzymatic degradation. Previous work by us has shown that PvdQ acylase hydrolyzes AHL signaling molecules irreversibly, thereby inhibiting QS in P. aeruginosa in vitro and in a Caenorhabditis elegans model of P. aeruginosa infection. The aim of the present study is to assess the therapeutic efficacy of intranasally instilled PvdQ acylase in a mouse model of pulmonary P. aeruginosa infection. First, we evaluated the deposition pattern of intranasally administered fluorochrome-tagged PvdQ (PvdQ-VT) in mice at different stages of pulmonary infection by in vivo imaging studies. Following intranasal instillation, PvdQ-VT could be traced in all lung lobes with 42 ± 7.5% of the delivered dose being deposited at 0 h post-bacterial-infection, and 34 ± 5.2% at 72 h post bacterial-infection. We then treated mice with PvdQ during lethal P. aeruginosa pulmonary infection and that resulted in a 5-fold reduction of lung bacterial load and a prolonged survival of the infected animals with the median survival time of 57 hin comparison to 42 h for the PBS-treated group. In a sublethal P. aeruginosa pulmonary infection, PvdQ treatment resulted in less lung inflammation as well as decrease of CXCL2 and TNF-α levels at 24 h post-bacterial-infection by 15 and 20%, respectively. In conclusion, our study has shown therapeutic efficacy of PvdQ acylase as a quorum quenching agent during P. aeruginosa infection.

Dataset Information

Reducing the virulence of Pseudomonas aeruginosa by using multiple quorum-quenching enzymes.

One-sentence summary

Publications

Reducing the virulence of Pseudomonas aeruginosa by using multiple quorum-quenching enzymes.

Similar Datasets

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