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A novel metagenomic short-chain dehydrogenase/reductase attenuates Pseudomonas aeruginosa biofilm formation and virulence on Caenorhabditis elegans.

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.
AuthorsPatrick Bijtenhoorn, Hubert Mayerhofer, Jochen Müller-Dieckmann, Christian Utpatel, Christina Schipper, Claudia Hornung, Matthias Szesny, Stephanie Grond, Andrea Thürmer, Elzbieta Brzuszkiewicz, Rolf Daniel, Katja Dierking, Hinrich Schulenburg, Wolfgang R Streit
JournalPloS one (PLoS One) Vol. 6 Issue 10 Pg. e26278 ( 2011) ISSN: 1932-6203 [Electronic] United States
PMID22046268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bacterial Proteins
  • NADP
  • Pyocyanine
  • Oxidoreductases
Topics
  • Animals
  • Bacterial Proteins (physiology)
  • Biofilms (drug effects)
  • Caenorhabditis elegans (microbiology)
  • Gene Expression Profiling
  • Metagenomics
  • NADP
  • Oxidoreductases (isolation & purification, pharmacology, physiology)
  • Pseudomonas Infections (immunology)
  • Pseudomonas aeruginosa (enzymology, growth & development, pathogenicity)
  • Pyocyanine (metabolism)
  • Quorum Sensing (drug effects)
  • Virulence

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