Role of ADP-ribosyltransferase activity of pertussis toxin in toxin-adhesin redundancy with filamentous hemagglutinin during Bordetella pertussis infection

Citation
S. Alonso et al., Role of ADP-ribosyltransferase activity of pertussis toxin in toxin-adhesin redundancy with filamentous hemagglutinin during Bordetella pertussis infection, INFEC IMMUN, 69(10), 2001, pp. 6038-6043
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INFECTION AND IMMUNITY
ISSN journal
0019-9567 → ACNP
Volume
69
Issue
10
Year of publication
2001
Pages
6038 - 6043
Database
ISI
SICI code
0019-9567(200110)69:10<6038:ROAAOP>2.0.ZU;2-4
Abstract
Pertussis toxin (PT) and filamentous hemagglutinin (FHA) are two major viru lence factors of Bordetella pertussis. FRA is the main adhesin, whereas PT is a toxin with an A-B structure, in which the A protomer expresses ADP-rib osyltransferase activity and the B moiety is responsible for binding to the target cells. Here, we show redundancy of FHA and PT during infection. Whe reas PT-deficient and FHA-deficient mutants colonized the mouse respiratory tract nearly as efficiently as did the isogenic parent strain, a mutant de ficient for both factors colonized substantially less well. This was not du e to redundant functions of PT and FRA 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 i nactive PT colonized as poorly as did the FHA-deficient, PT-deficient strai n, indicating that the ADP-ribosyltransferase activity of PT is required fo r redundancy with FRA. Only strains producing active PT induced a local tra nsient release of tumor necrosis factor alpha (TNF-alpha), suggesting that the pharmacological effects of PT are the basis of the redundancy with FRA, 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.