A Novel Metagenomic Short-Chain Dehydrogenase/Reductase Attenuates Pseudomonas aeruginosa Biofilm Formation and Virulence on Caenorhabditis elegans

Bijtenhoorn, P., Mayerhofer, H., Muller-Dieckmann, J., Utpatel, C., Schipper, C., Hornung, C., Szesny, M., Grond, S., Thurmer, A., Brzuszkiewicz, E., Daniel, R., Dierking, K., Schulenburg, H. and Streit, W. R. (2011) A Novel Metagenomic Short-Chain Dehydrogenase/Reductase Attenuates Pseudomonas aeruginosa Biofilm Formation and Virulence on Caenorhabditis elegans PLoS ONE, 6 (10). DOI e26278 10.1371/journal.pone.0026278.

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Abstract

In Pseudomonas aeruginosa, the expression of a number of virulence factors, as well as biofilm formation, are controlled by quorum sensing (QS). N-Acylhomoserine lactones (AHLs) are an important class of signaling molecules involved in bacterial QS and in many pathogenic bacteria infection and host colonization are AHL-dependent. The AHL signaling molecules are subject to inactivation mainly by hydrolases (Enzyme Commission class number EC 3) (i.e. N-acyl-homoserine lactonases and N-acyl-homoserine-lactone acylases). Only little is known on quorum quenching mechanisms of oxidoreductases (EC 1). Here we report on the identification and structural characterization of the first NADP-dependent short-chain dehydrogenase/reductase (SDR) involved in inactivation of N-(3-oxo-dodecanoyl)-L-homoserine lactone (3-oxo-C(12)-HSL) and derived from a metagenome library. The corresponding gene was isolated from a soil metagenome and designated bpiB09. Heterologous expression and crystallographic studies established BpiB09 as an NADP-dependent reductase. Although AHLs are probably not the native substrate of this metagenome-derived enzyme, its expression in P. aeruginosa PAO1 resulted in significantly reduced pyocyanin production, decreased motility, poor biofilm formation and absent paralysis of Caenorhabditis elegans. Furthermore, a genome-wide transcriptome study suggested that the level of lasI and rhlI transcription together with 36 well known QS regulated genes was significantly (>= 10-fold) affected in P. aeruginosa strains expressing the bpiB09 gene in pBBR1MCS-5. Thus AHL oxidoreductases could be considered as potent tools for the development of quorum quenching strategies.

Document Type: Article
Keywords: acyl-homoserine lactone n-acylhomoserine lactonase sp strain conjugal transfer ti plasmid dehydrogenases/reductases identification sdr expression genomes
Research affiliation: Kiel University
Refereed: Yes
DOI etc.: e26278 10.1371/journal.pone.0026278
ISSN: 1932-6203
Date Deposited: 01 Nov 2012 05:01
Last Modified: 23 Jan 2013 10:03
URI: http://eprints.uni-kiel.de/id/eprint/16810

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