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Infect Immun, June 1998, p. 2762-2768, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Neither the Bvgminus Phase nor the vrg6 Locus of Bordetella pertussis Is Required for Respiratory Infection in Micedagger

Guillermo Martinez de Tejada,1,Dagger Peggy A. Cotter,1,* Ulrich Heininger,1,§ Andrew Camilli,2 Brian J. Akerley,3 John J. Mekalanos,3 and Jeff F. Miller1

Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California 90095-17471; Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 021153; and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111-18002

Received 26 November 1997/Returned for modification 20 February 1998/Accepted 5 March 1998

In Bordetella species, the BvgAS sensory transduction system mediates an alteration between the Bvg+ phase, characterized by expression of adhesins and toxins, and the Bvg- phase, characterized by the expression of motility and coregulated phenotypes in Bordetella bronchiseptica and by the expression of vrg loci in Bordetella pertussis. Since there is no known environmental or animal reservoir for B. pertussis, the causative agent of whooping cough, it has been assumed that this phenotypic alteration must occur within the human host during infection. Consistent with this hypothesis was the observation that a B. pertussis mutant, SK6, containing a TnphoA insertion mutation in a Bvg-repressed gene (vrg6) was defective for tracheal and lung colonization in a mouse model of respiratory infection (D. T. Beattie, R. Shahin, and J. Mekalanos, Infect. Immun. 60:571-577, 1992). This result was inconsistent, however, with the observation that a Bvg+ phase-locked B. bronchiseptica mutant was indistinguishable from the wild type in its ability to establish a persistent respiratory infection in rabbits and rats (P. A. Cotter and J. F. Miller, Infect. Immun. 62:3381-3390, 1994; B. J. Akerley, P. A. Cotter, and J. F. Miller, Cell 80:611-620, 1995). To directly address the role of Bvg-mediated signal transduction in B. pertussis pathogenesis, we constructed Bvg+ and Bvg- phase-locked mutants and compared them with the wild type for their ability to colonize the respiratory tracts of mice. Our results show that the Bvg+ phase of B. pertussis is necessary and sufficient for respiratory infection. By constructing a strain with a deletion in the bvgR regulatory locus, we also show that ectopic expression of Bvg- phase phenotypes decreases the efficiency of colonization, underscoring the importance of Bvg-mediated repression of gene expression in vivo. Finally, we show that the virulence defect present in strain SK6 cannot be attributed to the vrg6 mutation. These data contradict an in vivo role for the Bvg- phase of B. pertussis.


* Corresponding author. Mailing address: Dept. of Microbiology and Immunology, UCLA School of Medicine, 10833 LeConte Ave., Los Angeles, CA 90095-1747. Phone: (310) 206-0319. Fax: (310) 206-3865. E-mail: pcotter{at}ucla.edu.

dagger This paper is dedicated to the memory of Roberta Shahin.

Dagger Present address: Departmento de Microbiologia, Universidad de Navarra, 31080 Pamplona, Spain.

§ Present address: Universitatsklinik fur Kinder und Jugendliche, Erlangen, Germany.


Infect Immun, June 1998, p. 2762-2768, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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