The LasB Elastase of Pseudomonas aeruginosa Acts in Concert with Alkaline Protease AprA To Prevent Flagellin-Mediated Immune Recognition.
The opportunistic pathogen Pseudomonas aeruginosa is capable of establishing severe and persistent infections in various eukaryotic hosts. It encodes a wide array of virulence factors and employs several strategies to evade immune detection. In the present study, we screened the Harvard Medical School transposon mutant library of P. aeruginosa PA14 for bacterial factors that modulate interleukin-8 responses in A549 human airway epithelial cells. We found that in addition to the previously identified alkaline protease AprA, the elastase LasB is capable of degrading exogenous flagellin under calcium-replete conditions and prevents flagellin-mediated immune recognition. Our results indicate that the production of two proteases with anti-flagellin activity provides a failsafe mechanism for P. aeruginosa to ensure the maintenance of protease-dependent immune-modulating functions.
Institute for Molecular Bacteriology, Twincore-Centre for Experimental and Clinical Infection Research, a joint venture of the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Fiordiligie
F
Casilag
Institute for Molecular Bacteriology, Twincore-Centre for Experimental and Clinical Infection Research, a joint venture of the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Anne
A
Lorenz
Institute for Molecular Bacteriology, Twincore-Centre for Experimental and Clinical Infection Research, a joint venture of the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Jonas
J
Krueger
Department of Biostatistics, Helmholtz Centre for Infection Research, Braunschweig, Germany Department of Computer Science, Ostfalia University of Applied Sciences, Wolfenbüttel, Germany.
Frank
F
Klawonn
Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Siegfried
S
Weiss
Institute for Molecular Bacteriology, Twincore-Centre for Experimental and Clinical Infection Research, a joint venture of the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Susanne.haeussler@helmholtz-hzi.de.
Susanne
S
Häussler
D001426:Bacterial Proteins / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology; D005407:Flagella / Q000276:immunology; D005408:Flagellin / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D016209:Interleukin-8 / Q000276:immunology; D008666:Metalloendopeptidases / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D012697:Serine Endopeptidases / Q000378:metabolism; D037521:Virulence Factors
D001426:Bacterial Proteins; C508606:CXCL8 protein, human; D016209:Interleukin-8; D037521:Virulence Factors; D005408:Flagellin; D010450:Endopeptidases; D012697:Serine Endopeptidases; C032923:microbial serine proteinases; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa; C087822:alkaline protease