PvdQ Quorum Quenching Acylase Attenuates Pseudomonas aeruginosa Virulence in a Mouse Model of Pulmonary Infection

Frontiers in Cellular and Infection Microbiology
Putri D UtariWim J Quax

Abstract

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 4...Continue Reading

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Citations

Jan 14, 2020·Applied Microbiology and Biotechnology·E PaluchK Jermakow
Aug 5, 2020·Expert Review of Anti-infective Therapy·Rakesh Sikdar, Mikael Elias
Aug 18, 2020·FEMS Microbiology Reviews·Astra Heywood, Iain L Lamont
Nov 19, 2019·Frontiers in Microbiology·Paweł Krzyżek
Jun 2, 2020·Frontiers in Cellular and Infection Microbiology·Allison L Welp, Jennifer M Bomberger
Nov 21, 2020·International Journal of Molecular Sciences·Minh Tam Tran ThiBernd H A Rehm
Feb 20, 2021·Canadian Journal of Microbiology·Celine Stoica, Georgina Cox

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Methods Mentioned

BETA
biosensors
gel filtration
biosensor
bronchoalveolar
lavage
Fluorescence
bronchoalveolar lavage
ELISA

Software Mentioned

[UNK]
SPSS
Living Image®
Graphpad Prism

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