Editors' ChoiceBacterial Signaling

Strained Communication

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Science Translational Medicine  03 Oct 2012:
Vol. 4, Issue 154, pp. 154ec178
DOI: 10.1126/scitranslmed.3005013

The bacterium Pseudomonas aeruginosa is an opportunistic pathogen that is commonly found in the environment and causes infections of the human lung, skin, eye, and gut. Strain variation among the different P. aeruginosa infections is well documented and is assumed to arise from adaptation for one specific behavior. Now, Chugani and co-workers show that this strain variation extends to changes in complex networks that control cascades of differentially regulated genes.

Quorum sensing (QS) is a signaling mechanism used to synchronize gene expression among bacteria in response to population density. Several prior studies showed that multiple P. aeruginosa virulence factors, colonization traits, and other genes important for infection are controlled by QS. The possibility of limiting virulence and controlling infection by targeting P. aeruginosa QS mechanisms with a drug remains an appealing therapeutic strategy.

In the new study, the authors showed that the expression of genes that control QS diverges among P. aeruginosa strains isolated from different infections and other settings. First, they sequenced genomic DNA from six P. aeruginosa strains (two cystic fibrosis lung isolates and one isolate each from soil, air, tomato, and a water-treatment biofilm) and compared these sequences with a commonly studied laboratory strain, PAO1, derived from a wound infection. A core genome of about 4500 genes was identified among these seven strains, which contain a total of 5486 to 5923 genes each. Next, an RNA-seq strategy was used to examine QS-dependent gene transcripts—each strain was compared with its isogenic mutant deficient for QS signal production. Here, the results varied widely: PAO1 was found to have 161 QS-activated genes, and the other isolates ranged from 31 to 342 activated genes. The two cystic fibrosis lung isolates showed some of the greatest divergence in well-known virulence factors, such as elastase and hydrogen cyanide–producing enzymes, which were very differently regulated (or even absent) in comparison to PAO1.

The potential to mine individual human genomes to improve medical care has generated a great deal of excitement in recent years. This study highlights how similar genomic approaches to examine the agents of infection can also yield valuable information. Further work will be needed to analyze additional strains of P. aeruginosa and other pathogens and to develop therapeutic strategies based on the new findings about their virulence genes. However, now that we can identify specific regulatory circuits of these pathogens, we have opened the door for new genomics-driven therapeutic strategies.

S. Chugani et al., Strain-dependent diversity in the Pseudomonas aeruginosa quorum-sensing regulon. Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1214128109 (2012). [Abstract]

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