title: Pertussis toxin and adenylate cyclase toxin provide a one-two punch for establishment of Bordetella pertussis infection of the respiratory tract.
abstract: Previously we found that pertussis toxin (PT), an exotoxin virulence factor produced by Bordetella pertussis, plays an important early role in colonization of the respiratory tract by this pathogen, using a mouse intranasal infection model. In this study, we examined the early role played by another exotoxin produced by this pathogen, adenylate cyclase toxin (ACT). By comparing a wild-type strain to a mutant strain (DeltaCYA) with an in-frame deletion of the cyaA gene encoding ACT, we found that the lack of ACT confers a significant peak (day 7) colonization defect (1 to 2 log(10)). In mixed-infection experiments, the DeltaCYA strain was significantly outcompeted by the wild-type strain, and intranasal administration of purified ACT did not increase colonization by DeltaCYA. These data suggest that ACT benefits the bacterial cells that produce it and, unlike PT, does not act as a soluble factor benefiting the entire infecting bacterial population. Comparison of lower respiratory tract infections over the first 4 days after inoculation revealed that the colonization defect of the PT deletion strain was apparent earlier than that of DeltaCYA, suggesting that PT plays an earlier role than ACT in the establishment of B. pertussis infection. Examination of cells in the bronchoalveolar lavage fluid of infected mice revealed that, unlike PT, ACT does not appear to inhibit neutrophil influx to the respiratory tract early after infection but may combat neutrophil activity once influx has occurred.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 655 W. Baltimore St., BRB13-009, Baltimore, MD 21201, USA. ncarbone@umaryland.edu
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Carbonetti
authors.forename: Galina V
authors.initials: GV
authors.lastname: Artamonova
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andreasen
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bushar
mesh_terms: D037361:Adenylate Cyclase Toxin / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001886:Bordetella pertussis / Q000472:pathogenicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects*; D037342:Pertussis Toxin / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D014917:Whooping Cough / Q000276:immunology* / Q000382:microbiology
chemical_list: D037361:Adenylate Cyclase Toxin; D037342:Pertussis Toxin