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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 Bvg
Phase nor the
vrg6 Locus of Bordetella pertussis Is Required
for Respiratory Infection in Mice
Guillermo
Martinez de
Tejada,1,
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.

This paper is dedicated to the memory of Roberta Shahin.

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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