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Infection and Immunity, April 2001, p. 1983-1993, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.1983-1993.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Differential Regulation of Bvg-Activated Virulence Factors Plays a Role in Bordetella pertussis Pathogenicity

Susan M. Kinnear, Ryan R. Marques,dagger and Nicholas H. Carbonetti*

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

Received 28 June 2000/Returned for modification 2 October 2000/Accepted 18 December 2000

Bordetella pertussis, the causative agent of whooping cough, regulates expression of many virulence factors via a two-component signal transduction system encoded by the bvgAS regulatory locus. It has been shown by transcription activation kinetics that several of the virulence factors are differentially regulated. fha is transcribed within 10 min following a bvgAS-inducing signal, while prn is transcribed after 1 h and ptx is not transcribed until 2 to 4 h after induction. These genes therefore represent early, intermediate, and late classes of bvg-activated promoters, respectively. Although there have been many insightful studies into the mechanisms of BvgAS-mediated regulation, the role that differential regulation of virulence genes plays in B. pertussis pathogenicity has not been characterized. We provide evidence that alterations to the promoter regions of bvg-activated genes can alter the kinetic pattern of expression of these genes without changing steady-state transcription levels. In addition, B. pertussis strains containing these promoter alterations that express either ptx at an early time or fha at a late time demonstrate a significant reduction in their ability to colonize respiratory tracts in an intranasal mouse model of infection. These data suggest a role for differential regulation of bvg-activated genes, and therefore for the BvgAS regulatory system, in the pathogenicity of B. pertussis.


* Corresponding author. Mailing address: University of Maryland School of Medicine, Department of Microbiology and Immunology, BRB 13-009, 655 W. Baltimore St., Baltimore, MD 21201-1559. Phone: (410) 706-7677. Fax: (410) 706-2129. E-mail: ncarbone{at}umaryland.edu.

dagger Present address: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201.


Infection and Immunity, April 2001, p. 1983-1993, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.1983-1993.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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