Journal
CRITICAL CARE MEDICINE
Volume 37, Issue 5, Pages 1777-1786Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0b013e31819ff137
Keywords
Pseudomonas aeruginosa; virulence factors; type III secretion; quorum sensing; biofilms; flagella; adjunctive therapy
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Funding
- AGAUR [05SGR920]
- Marato [TV3]
- National Institutes of Health [1101 A1053674]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI075191, K02AI065615, R01AI053674] Funding Source: NIH RePORTER
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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. (Crit Care Med 2009; 37:1777-1786)
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