Effects of the Twin-Arginine Translocase on Secretion of Virulence Factors, Stress Response, and Pathogenesis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 12; pp. 8312 - 8317
• Main Authors: Ochsner, Urs A., Snyder, Aleksandra, Vasil, Adriana I., Vasil, Michael L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 11.06.2002; National Acad Sciences; The National Academy of Sciences
• Subjects: Aldehydes; Amino Acid Sequence; Animals; Bacteria; Bacterial Proteins - pharmacology; Biofilms; Biological Sciences; Enzymes; Escherichia coli Proteins - metabolism; Gene Deletion; Gene Expression Regulation, Bacterial; Genes; Infections; Lung - microbiology; Lung - pathology; Lungs; Membrane Transport Proteins - metabolism; Microbiology; Molecular Sequence Data; Nitrates; Oligopeptides; Phenotype; Phenotypes; Pigments, Biological - pharmacology; Protein Sorting Signals; Proteins; Pseudomonas aeruginosa - enzymology; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - pathogenicity; Rats; Secretion; Type C Phospholipases - genetics; Virulence; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.082238299

A novel secretion pathway originally found in plants has recently been discovered in bacteria and termed TAT, for "twin-arginine translocation," with respect to the presence of an Arg-Arg motif in the signal sequence of TAT-secreted products. However, it is unknown whether the TAT system contributes in any way to virulence through the secretion of factors associated with pathogenesis or stress response. We found that the opportunistic pathogen Pseudomonas aeruginosa produces several virulence factors that depend on the TAT system for proper export to the periplasm, outer membrane, or extracellular milieu. We identified at least 18 TAT substrates of P. aeruginosa and characterized the pleiotropic phenotypes of a tatC deletion mutant. The TAT system proved essential for the export of phospholipases, proteins involved in pyoverdine-mediated iron-uptake, anaerobic respiration, osmotic stress defense, motility, and biofilm formation. Because all these traits have been associated with virulence, we studied the role of TAT in a rat lung model. A tatC mutant did not cause the typical multifocal pulmonary abscesses and did not evoke a heavy inflammatory host response compared with wild type, indicating that tatC mutant cells are attenuated for virulence. Because the TAT apparatus is well conserved among important bacterial pathogens yet absent in mammalian cells, it represents a potential target for novel antimicrobial compounds.