Immune evasion of the human pathogen Pseudomonas aeruginosa: elongation factor Tuf is a factor H and plasminogen binding protein.
Pseudomonas aeruginosa is an opportunistic human pathogen that can cause a wide range of clinical symptoms and infections that are frequent in immunocompromised patients. In this study, we show that P. aeruginosa evades human complement attack by binding the human plasma regulators Factor H and Factor H-related protein-1 (FHR-1) to its surface. Factor H binds to intact bacteria via two sites that are located within short consensus repeat (SCR) domains 6-7 and 19-20, and FHR-1 binds within SCR domain 3-5. A P. aeruginosa Factor H binding protein was isolated using a Factor H affinity matrix, and was identified by mass spectrometry as the elongation factor Tuf. Factor H uses the same domains for binding to recombinant Tuf and to intact bacteria. Factor H bound to recombinant Tuf displayed cofactor activity for degradation of C3b. Similarly Factor H bound to intact P. aeruginosa showed complement regulatory activity and mediated C3b degradation. This acquired complement control was rather effective and acted in concert with endogenous proteases. Immunolocalization identified Tuf as a surface protein of P. aeruginosa. Tuf also bound plasminogen, and Tuf-bound plasminogen was converted by urokinase plasminogen activator to active plasmin. Thus, at the bacterial surface Tuf acts as a virulence factor and binds the human complement regulator Factor H and plasminogen. Acquisition of host effector proteins to the surface of the pathogen allows complement control and may facilitate tissue invasion.
Kunert
Anja
A
Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology (Hans-Knoell-Institute), Beutenbergstrasse 11a, 07745 Jena, Germany.
Losse
Josephine
J
Gruszin
Christin
C
Hühn
Michael
M
Kaendler
Kerstin
K
Mikkat
Stefan
S
Volke
Daniela
D
Hoffmann
Ralf
R
Jokiranta
T Sakari
TS
Seeberger
Harald
H
Moellmann
Ute
U
Hellwage
Jens
J
Zipfel
Peter F
PF
D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000276:immunology* / Q000302:isolation & purification; D001798:Blood Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000032:analysis / Q000276:immunology* / Q000302:isolation & purification; D002460:Cell Line; D017242:Complement Factor H / Q000276:immunology*; D006801:Humans; D010444:Peptide Elongation Factor Tu / Q000032:analysis / Q000276:immunology* / Q000302:isolation & purification; D010958:Plasminogen / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity*; D011994:Recombinant Proteins / Q000276:immunology; D014774:Virulence
D001426:Bacterial Proteins; D001798:Blood Proteins; D002352:Carrier Proteins; D011994:Recombinant Proteins; C100631:factor H-related protein 1; C084529:plasminogen-binding protein, bacteria; D017242:Complement Factor H; D010958:Plasminogen; D010444:Peptide Elongation Factor Tu