A Novel Virulence Strategy for Pseudomonas aeruginosa Mediated by an Autotransporter with Arginine-Specific Aminopeptidase Activity

PLoS Pathogens

Manal AbuOun¹  Kendra P. Rumbaugh²  Chase Watters²  Stephan Heeb³  Victoria Wright³  Esteban Paredes-Osses³  Stéphanie Pommier³  Owen Darch³  Jenny Ward³  Jeni C. A. Luckett³  Miguel Cámara³  Kim R. Hardie³  Hana Goto³ 

[1] Department of Bacteriology, Animal Health and Veterinary Laboratories Agency (Weybridge), Addlestone, Surrey, United Kingdom;Department of Surgery, MS 8312, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America;School of Molecular Medical Sciences, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, United Kingdom

关键词: Pseudomonas aeruginosa;    Arginine;    Skin infections;    Proteases;    Outer membrane proteins;    Serine proteases;    Immunoblotting;    Pathogenesis;   

DOI  :  10.1371/journal.ppat.1002854

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY