Interaction of human Tamm-Horsfall glycoprotein with Bordetella pertussis toxin.
Tamm-Horsfall glycoprotein (THP), which is synthesized by renal tubular cells, is the most abundant protein in normal human urine. Although its physiological function remains unclear, it has been proposed that THP may act as a defence factor against urinary tract infections by inhibiting the binding of S- and P-fimbriated Escherichia coli to renal epithelial cells. Because THP-related proteins are also found in the superficial layers of the oral mucosa, the authors investigated the ability of THP to interfere with the cytoadherence of pathogenic bacteria that colonize mucosal surfaces other than those of the urogenital tract. In this report, it is shown that THP binds to virulent Bordetella pertussis and reduces its adherence to both renal and pulmonary epithelial cells. This cytoadherence inhibitory effect was not observed with a B. pertussis mutant lacking the pertussis toxin (PTX) operon, and was dependent on the direct interaction of THP with the S2 subunit within the PTX B oligomer. The authors also show that the glycosylation moiety of THP is crucial for its binding to PTX. The THP-PTX interaction was exploited to develop an affinity chromatography method that allows a one-step purification of active PTX. These observations suggest that besides its anti-adherence activity, THP may also trap toxins produced by pathogenic bacteria that colonize mucosal surfaces.
Menozzi
Franco D
FD
Institut Pasteur de Lille, INSERM U447, Mécanismes moléculaires de la pathogénie microbienne, 1 Rue du Professeur Calmette, 59019 Lille Cedex, France1.
Debrie
Anne-Sophie
AS
Institut Pasteur de Lille, INSERM U447, Mécanismes moléculaires de la pathogénie microbienne, 1 Rue du Professeur Calmette, 59019 Lille Cedex, France1.
Tissier
Jean-Pierre
JP
Institut National de la Recherche Agronomique, Laboratoire de Génie des Procédés et Technologie Alimentaires, 369 Rue Jules Guesde, 59651 Villeneuve d'Ascq, France2.
Locht
Camille
C
Institut Pasteur de Lille, INSERM U447, Mécanismes moléculaires de la pathogénie microbienne, 1 Rue du Professeur Calmette, 59019 Lille Cedex, France1.
Pethe
Kevin
K
Institut Pasteur de Lille, INSERM U447, Mécanismes moléculaires de la pathogénie microbienne, 1 Rue du Professeur Calmette, 59019 Lille Cedex, France1.
Raze
Dominique
D
Institut Pasteur de Lille, INSERM U447, Mécanismes moléculaires de la pathogénie microbienne, 1 Rue du Professeur Calmette, 59019 Lille Cedex, France1.
D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001886:Bordetella pertussis / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D002460:Cell Line; D004285:Dogs; D006801:Humans; D009061:Mouth Mucosa / Q000502:physiology; D009088:Mucoproteins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D037342:Pertussis Toxin; D021122:Protein Subunits; D058949:Uromodulin; D019459:Urothelium / Q000382:microbiology; D014774:Virulence; D010566:Virulence Factors, Bordetella / Q000378:metabolism*
D009088:Mucoproteins; D021122:Protein Subunits; C548612:UMOD protein, human; D058949:Uromodulin; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin