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A novel virulence strategy for Pseudomonas aeruginosa mediated by an autotransporter with arginine-specific aminopeptidase activity

Luckett, Jeni; Darch, Owen; Watters, Chase; AbuOun, Manal; Wright, Victoria; Paredes-Osses, Esteban; Ward, Jenny; Goto, Hana; Heeb, Stephan; Pommier, Stéphanie; Rumbaugh, Kendra P.; Cámara, Miguel; Hardie, Kim R.

Authors

Jeni Luckett

Owen Darch

Chase Watters

Manal AbuOun

Victoria Wright

Esteban Paredes-Osses

Jenny Ward

Hana Goto

Stephan Heeb

Stéphanie Pommier

Kendra P. Rumbaugh

Miguel Cámara

Kim R. Hardie

Abstract

The opportunistic human pathogen, Pseudomonas aeruginosa, is a major cause of infections in chronic wounds, burns and the lungs of cystic fibrosis patients. The P. aeruginosa genome encodes at least three proteins exhibiting the characteristic three domain structure of autotransporters, but much remains to be understood about the functions of these three proteins and their role in pathogenicity. Autotransporters are the largest family of secreted proteins in Gram-negative bacteria, and those characterised are virulence factors. Here, we demonstrate that the PA0328 autotransporter is a cell-surface tethered, arginine-specific aminopeptidase, and have defined its active site by site directed mutagenesis. Hence, we have assigned PA0328 with the name AaaA, for arginine-specific autotransporter of P. aeruginosa. We show that AaaA provides a fitness advantage in environments where the sole source of nitrogen is peptides with an aminoterminal arginine, and that this could be important for establishing an infection, as the lack of AaaA led to attenuation in a mouse chronic wound infection which correlated with lower levels of the cytokines TNFα, IL-1α, KC and COX-2. Consequently AaaA is an important virulence factor playing a significant role in the successful establishment of P. aeruginosa infections.

Journal Article Type Article
Publication Date Aug 23, 2012
Journal PloS Pathogens
Print ISSN 1553-7366
Electronic ISSN 1553-7374
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 8
Issue 8
Article Number e1002854
Institution Citation Luckett, J., Darch, O., Watters, C., AbuOun, M., Wright, V., Paredes-Osses, E., …Hardie, K. R. (2012). A novel virulence strategy for Pseudomonas aeruginosa mediated by an autotransporter with arginine-specific aminopeptidase activity. PLoS Pathogens, 8(8), doi:10.1371/journal.ppat.1002854
DOI https://doi.org/10.1371/journal.ppat.1002854
Publisher URL http://www.plospathogens.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1002854&representation=PDF
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0




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