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Infection and Immunity, November 2003, p. 6358-6366, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6358-6366.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Pertussis Toxin Plays an Early Role in Respiratory Tract Colonization by Bordetella pertussis

Department of Microbiology and Immunology, University of Maryland Medical School, Baltimore, Maryland 21201

Received 2 July 2003/ Returned for modification 28 July 2003/ Accepted 6 August 2003

In this study, we sought to determine whether pertussis toxin (PT), an exotoxin virulence factor produced exclusively by Bordetella pertussis, is important for colonization of the respiratory tract by this pathogen by using a mouse intranasal infection model. By comparing a wild-type Tohama I strain to a mutant strain with an in-frame deletion of the ptx genes encoding PT (PT), we found that the lack of PT confers a significant peak (day 7) colonization defect (1 to 2 log₁₀ units) over a range of bacterial inoculum doses and that this defect was apparent within 1 to 2 days postinoculation. In mixed-strain infection experiments, the PT strain showed no competitive disadvantage versus the wild-type strain and colonized at higher levels than in the single-strain infection experiments. To test the hypothesis that soluble PT produced by the wild-type strain in mixed infections enhanced respiratory tract colonization by PT, we coadministered purified PT with the PT inoculum and found that colonization was increased to wild-type levels. This effect was not observed when PT was coadministered via a systemic route. Intranasal administration of purified PT up to 14 days prior to inoculation with PT significantly increased bacterial colonization, but PT administration 1 day after bacterial inoculation did not enhance colonization versus a phosphate-buffered saline control. Analysis of bronchoalveolar lavage fluid samples from mice infected with either wild-type or PT strains at early times after infection revealed that neutrophil influx to the lungs 48 h postinfection was significantly greater in response to PT infection, implicating neutrophil chemotaxis as a possible target of PT activity promoting B. pertussis colonization of the respiratory tract.

Editor: A. D. O'Brien

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