The LasB Elastase of Pseudomonas aeruginosa Acts in Concert with Alkaline Protease AprA To Prevent Flagellin-Mediated Immune Recognition

Fiordiligie Casilag; Anne Lorenz; Jonas Krueger; Frank Klawonn; Siegfried Weiss; Susanne Häussler

doi:10.1128/IAI.00939-15

The LasB Elastase of Pseudomonas aeruginosa Acts in Concert with Alkaline Protease AprA To Prevent Flagellin-Mediated Immune Recognition

Infect Immun. 2015 Oct 26;84(1):162-71. doi: 10.1128/IAI.00939-15. Print 2016 Jan.

Authors

Fiordiligie Casilag¹, Anne Lorenz², Jonas Krueger¹, Frank Klawonn³, Siegfried Weiss⁴, Susanne Häussler⁵

Affiliations

¹ 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.
² 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.
³ Department of Biostatistics, Helmholtz Centre for Infection Research, Braunschweig, Germany Department of Computer Science, Ostfalia University of Applied Sciences, Wolfenbüttel, Germany.
⁴ Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
⁵ 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.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bacterial Proteins / metabolism*
Endopeptidases / metabolism*
Epithelial Cells / immunology
Flagella / immunology
Flagellin / immunology*
Flagellin / metabolism
Humans
Immune Evasion / immunology*
Interleukin-8 / immunology
Metalloendopeptidases / metabolism*
Pseudomonas Infections / immunology
Pseudomonas Infections / microbiology
Pseudomonas aeruginosa / immunology*
Pseudomonas aeruginosa / pathogenicity
Serine Endopeptidases / metabolism
Virulence Factors

Substances

Bacterial Proteins
CXCL8 protein, human
Interleukin-8
Virulence Factors
Flagellin
Endopeptidases
Serine Endopeptidases
microbial serine proteinases
Metalloendopeptidases
pseudolysin, Pseudomonas aeruginosa
alkaline protease

Grants and funding

The European Research Council (ERC) provided a starter grant to Susanne Häussler under the number Resistome 260276. Further funding was provided by the Ministry for for Science and Culture of Lower Saxony via the Georg Lichtenberg Scholarship.