Role of ADP-ribosyltransferase activity of pertussis toxin in toxin-adhesin redundancy with filamentous hemagglutinin during Bordetella pertussis infection.
Pertussis toxin (PT) and filamentous hemagglutinin (FHA) are two major virulence factors of Bordetella pertussis. FHA is the main adhesin, whereas PT is a toxin with an A-B structure, in which the A protomer expresses ADP-ribosyltransferase activity and the B moiety is responsible for binding to the target cells. Here, we show redundancy of FHA and PT during infection. Whereas PT-deficient and FHA-deficient mutants colonized the mouse respiratory tract nearly as efficiently as did the isogenic parent strain, a mutant deficient for both factors colonized substantially less well. This was not due to redundant functions of PT and FHA as adhesins, since in vitro studies of epithelial cells and macrophages indicated that FHA, but not PT, acts as an adhesin. An FHA-deficient B. pertussis strain producing enzymatically inactive PT colonized as poorly as did the FHA-deficient, PT-deficient strain, indicating that the ADP-ribosyltransferase activity of PT is required for redundancy with FHA. Only strains producing active PT induced a local transient release of tumor necrosis factor alpha (TNF-alpha), suggesting that the pharmacological effects of PT are the basis of the redundancy with FHA, through the release of TNF-alpha. This may lead to damage of the pulmonary epithelium, allowing the bacteria to colonize even in the absence of FHA.
Alonso
S
S
INSERM U447, IBL, Institut Pasteur de Lille, F-59019 Lille, France.
Pethe
K
K
Mielcarek
N
N
Raze
D
D
Locht
C
C
D018829:Adhesins, Bacterial / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001886:Bordetella pertussis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D002460:Cell Line; D005260:Female; D006388:Hemagglutinins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000382:microbiology; D051379:Mice; D037342:Pertussis Toxin; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000378:metabolism*; D014917:Whooping Cough / Q000276:immunology / Q000382:microbiology
D018829:Adhesins, Bacterial; D006388:Hemagglutinins; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; D011065:Poly(ADP-ribose) Polymerases; D037342:Pertussis Toxin