viernes, noviembre 14, 2003

Y sigue la serie en Journal of Clinical Investigation sobre percepción de quorum (quorum sensing, QS)

Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target. Roger S. Smith and Barbara H. Iglewski. J. Clin. Invest. 112:1460-1465 (2003).

There are two QS systems in P. aeruginosa:
las system consists of the LasR transcriptional regulator and the LasI synthase protein in the presence of signal molecule AHL, LasR forms multimers, and that only the multimeric form of this protein is able to bind DNA and regulate the transcription of multiple genes.
RhlI and RhlR proteins: RhlI synthase, and RhlR is the transcriptional regulator .

The majority of the genes regulated by QS were found to be hypothetical or of unknown function. In all studies, a large number of the known genes were found to be probable virulence factors; however, several other identified genes may also fall into this category.QS regulates many genes via indirect mechanisms. A large number of the QS-regulated genes were classified as transcriptional regulators or as members of a two-component regulatory system

deletions of one or more QS genes result in reduced P. aeruginosa virulence compared with wild-type P. aeruginosa. QS has also been shown to be functional during P. aeruginosa infections in humans. In sputum samples from cystic fibrosis patients colonized with P. aeruginosa, levels of transcripts for QS genes were found to correlate with those of QS-regulated genes, indicating that QS was regulating their expression during infection

AHLs produced by P. aeruginosa are able to interact with eukaryotic cells and to stimulate the production of various factors that may affect the pathogenesis of this bacterium.

Several components of the QS networks represent ideal targets for potential therapeutics
a. A synthetic halogenated-furanone compound is able to inhibit the production of many QS-induced factors.
b. Antibodies specific for AHLs inhibit QS and may be useful as therapeutics
c. An alternative approach to the inhibition of QS is the use of antisense oligonucleotides that specifically bind to lasR/lasI or rhlR/rhlI transcripts and inhibit gene expression