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Pseudomonas aeruginosa virulence and therapy: Evolving translational strategies*

Veesenmeyer, Jeffrey L. BA; Hauser, Alan R. MD, PhD; Lisboa, Thiago MD; Rello, Jordi MD, PhD

doi: 10.1097/CCM.0b013e31819ff137
Review Articles
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Objective: Although most reviews of Pseudomonas aeruginosa therapeutics focus on antibiotics currently in use or in the pipeline, we review evolving translational strategies aimed at using virulence factor antagonists as adjunctive therapies.

Data Source: Current literature regarding P. aeruginosa virulence determinants and approaches that target them, with an emphasis on type III secretion, quorum-sensing, biofilms, and flagella.

Data Extraction and Synthesis: P. aeruginosa remains one of the most important pathogens in nosocomial infections, with high associated morbidity and mortality. Its predilection to develop resistance to antibiotics and expression of multiple virulence factors contributes to the frequent ineffectiveness of current therapies. Among the many P. aeruginosa virulence determinants that impact infections, type III secretion, quorum sensing, biofilm formation, and flagella have been the focus on much recent investigation. Here we review how increased understanding of these important bacterial structures and processes has enabled the development of novel approaches to inhibit each. These promising translational strategies may lead to the development of adjunctive therapies capable of improving outcomes.

Conclusions: Adjuvant therapies directed against virulence factors have the potential to improve outcomes in P. aeruginosa infections.

From the Departments of Microbiology/Immunology (JLV, ARH) and Medicine (ARH), Northwestern University, Chicago, IL; and Critical Care Department and CIBER Enfermedades Respiratorias (CIBERES) (TL, JR), Joan XXIII University Hospital, University Rovira i Virgili & Pere Virgili Health Institut, Tarragona, Spain.

Supported in part by AGAUR 05SGR920 (JR), a grant from Marato TV3 (JR), and the National Institutes of Health (R01 AI053674, ARH).

Dr. Rello consulted for Intercell. The remaining authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: jrello.hj23.ics@gencat.cat

© 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins