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Infection and Immunity, April 2001, p. 1983-1993, Vol. 69, No. 4
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.
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
and
*
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.
Present address: Center for Vaccine Development, University of
Maryland School of Medicine, Baltimore, MD 21201.
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