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Infection and Immunity, February 2008, p. 632-638, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01132-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Pseudomonas aeruginosa RsmA Plays an Important Role during Murine Infection by Influencing Colonization, Virulence, Persistence, and Pulmonary Inflammation

Heidi Mulcahy,^1, Julie O'Callaghan,¹ Eoin P. O'Grady,^1, María D. Maciá,² Nuria Borrell,² Cristina Gómez,³ Pat G. Casey,⁴ Colin Hill,⁴ Claire Adams,¹ Cormac G. M. Gahan,^4,5 Antonio Oliver,² and Fergal O'Gara^1*

BIOMERIT Research Centre, Department of Microbiology, University College Cork, Cork, Ireland,¹ Servicio de Microbiología and Unidad de Investigación, Hospital Son Dureta, Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Palma de Mallorca, Spain,² Servicio de Anatomía Patológica, Hospital Son Dureta, Palma de Mallorca, Spain,³ Department of Microbiology and Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland,⁴ School of Pharmacy, University College Cork, Cork, Ireland⁵

Received 14 August 2007/ Returned for modification 4 October 2007/ Accepted 5 November 2007

The ability of Pseudomonas aeruginosa to cause a broad range of infections in humans is due, at least in part, to its adaptability and its capacity to regulate the expression of key virulence genes in response to specific environmental conditions. Multiple two-component response regulators have been shown to facilitate rapid responses to these environmental conditions, including the coordinated expression of specific virulence determinants. RsmA is a posttranscriptional regulatory protein which controls the expression of a number of virulence-related genes with relevance for acute and chronic infections. Many membrane-bound sensors, including RetS, LadS, and GacS, are responsible for the reciprocal regulation of genes associated with acute infection and chronic persistence. In P. aeruginosa this is due to sensors influencing the expression of the regulatory RNA RsmZ, with subsequent effects on the level of free RsmA. While interactions between an rsmA mutant and human airway epithelial cells have been examined in vitro, the role of RsmA during infection in vivo has not been determined yet. Here the function of RsmA in both acute and chronic models of infection was examined. The results demonstrate that RsmA is involved in initial colonization and dissemination in a mouse model of acute pneumonia. Furthermore, while loss of RsmA results in reduced colonization during the initial stages of acute infection, the data show that mutation of rsmA ultimately favors chronic persistence and results in increased inflammation in the lungs of infected mice.

Published ahead of print on 19 November 2007.

Editor: V. J. DiRita

Present address: Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta T2N 4N1, Canada.