Quorum-quenching acylase reduces the virulence of Pseudomonas aeruginosa in a Caenorhabditis elegans infection model.
The Pseudomonas aeruginosa PAO1 gene pvdQ encodes an acyl-homoserine lactone (AHL) acylase capable of degrading N-(3-oxododecanoyl)-L-homoserine lactone by cleaving the AHL amide. PvdQ has been proven to function as a quorum quencher in vitro in a number of phenotypic assays. To address the question of whether PvdQ also shows quorum-quenching properties in vivo, an infection model based on the nematode Caenorhabditis elegans was explored. In a fast-acting paralysis assay, strain PAO1(pMEpvdQ), which overproduces PvdQ, was shown to be less virulent than the wild-type strain. More than 75% of the nematodes exposed to PAO1(pMEpvdQ) survived and continued to grow when using this strain as a food source. Interestingly, in a slow-killing assay monitoring the survival of the nematodes throughout a 4-day course, strain PAO1-Delta pvdQ was shown to be more virulent than the wild-type strain, confirming the role of PvdQ as a virulence-reducing agent. It was observed that larval stage 1 (L1) to L3-stage larvae benefit much more from protection by PvdQ than L4 worms. Finally, purified PvdQ protein was added to C. elegans worms infected with wild-type PAO1, and this resulted in reduced pathogenicity and increased the life span of the nematodes. From our observations we can conclude that PvdQ might be a strong candidate for antibacterial therapy against Pseudomonas infections.
Papaioannou
Evelina
E
Department of Pharmaceutical Biology, University of Groningen, 9713AV Groningen, The Netherlands.
Wahjudi
Mariana
M
Nadal-Jimenez
Pol
P
Koch
Gudrun
G
Setroikromo
Rita
R
Quax
Wim J
WJ
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000032:analysis; D054742:Acyl-Butyrolactones / Q000378:metabolism*; D000581:Amidohydrolases / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000382:microbiology*; D004195:Disease Models, Animal; D006714:Homoserine / Q000031:analogs & derivatives / Q000032:analysis; D006856:Hydrogen Cyanide / Q000633:toxicity; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000472:pathogenicity; D053038:Quorum Sensing; D014774:Virulence
D054742:Acyl-Butyrolactones; C109860:N-(3-oxododecanoyl)homoserine lactone; D006856:Hydrogen Cyanide; D006714:Homoserine; D000581:Amidohydrolases; C019665:amidase; D015107:4-Butyrolactone