TY  - JOUR
AB  - The opportunistic pathogen Pseudomonas aeruginosa employs quorum sensing to govern the production of many virulence factors. Interference with quorum sensing signaling has therefore been put forward as an attractive approach to disarm this pathogen. Here, we analyzed the quorum quenching properties of natural and engineered (2-alkyl-)3-hydroxy-4(1H)-quinolone 2,4-dioxygenases (HQDs) that inactivate the P. aeruginosa signal molecule PQS (Pseudomonas quinolone signal; 2-heptyl-3-hydroxy-4(1H)-quinolone). When added exogenously to P. aeruginosa cultures, all HQDs tested significantly reduced the levels of PQS and other alkylquinolone-type secondary metabolites deriving from the biosynthetic pathway, such as the respiratory inhibitor 2-heptyl-4-hydroxyquinoline N-oxide. HQDs from Nocardia farcinica and Streptomyces bingchenggensis, which combine low KM values for PQS with thermal stability and resilience in the presence of P. aeruginosa exoproducts, respectively, attenuated production of the virulence factors pyocyanin and pyoverdine. A delay in mortality was observed when Galleria mellonella larvae were infected with P. aeruginosa suspensions treated with the S. bingchenggensis HQD or with inhibitors of alkylquinolone biosynthesis. Our data indicate that quenching of PQS signaling has potential as an anti-virulence strategy; however, an efficient anti-virulence therapy against P. aeruginosa likely requires a combination of agents addressing multiple targets.
AU  - Arranz San Martín, Alba
AU  - Vogel, Jan
AU  - Wullich, Sandra C.
AU  - Quax, Wim J.
AU  - Fetzner, Susanne
DA  - 2022-01-21
KW  - dioxygenase
KW  - Galleria mellonella
KW  - Pseudomonas aeruginosa
KW  - Pseudomonas quinolone signal
KW  - quorum quenching
KW  - virulence
LA  - eng
N1  - Biomolecules 12 (2022) 2, 170, 1-12
N1  - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
N1  - Förderer: European Commission / Projektnummer: 722390
N1  - Funding organisation: European Commission / Project number: 722390
N1  - Förderer: European Commission / Projektnummer: 713482
N1  - Funding organisation: European Commission / Project number: 713482
PY  - 2022-01-21
TI  - Enzyme-Mediated Quenching of the Pseudomonas Quinolone Signal (PQS): A Comparison between Naturally Occurring and Engineered PQS-Cleaving Dioxygenases
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-64099408460
Y2  - 2024-11-22T06:49:54
ER  -