Neither the Bvg- phase nor the vrg6 locus of Bordetella pertussis is required for respiratory infection in mice
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 expressio...
Main Authors: | , , , , , , |
---|---|
Format: | info:eu-repo/semantics/article |
Language: | eng |
Published: |
American Society for Microbiology
2013
|
Subjects: | |
Online Access: | https://hdl.handle.net/10171/29517 |
_version_ | 1793400124804694016 |
---|---|
author | Martinez-de-Tejada, G. (Guillermo) Cotter, P.A. (Peggy A.) Heininger, U. (Ulrich) Camilli, A. (Andrew) Akerley, B.J. (Brian J.) Mekalanos, J.J. (John J.) Miller, J.F. (Jeff F.) |
author_facet | Martinez-de-Tejada, G. (Guillermo) Cotter, P.A. (Peggy A.) Heininger, U. (Ulrich) Camilli, A. (Andrew) Akerley, B.J. (Brian J.) Mekalanos, J.J. (John J.) Miller, J.F. (Jeff F.) |
author_sort | Martinez-de-Tejada, G. (Guillermo) |
collection | DSpace |
description | 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. |
format | info:eu-repo/semantics/article |
id | oai:dadun.unav.edu:10171-29517 |
institution | Universidad de Navarra |
language | eng |
publishDate | 2013 |
publisher | American Society for Microbiology |
record_format | dspace |
spelling | oai:dadun.unav.edu:10171-295172020-03-03T20:44:54Z Neither the Bvg- phase nor the vrg6 locus of Bordetella pertussis is required for respiratory infection in mice Martinez-de-Tejada, G. (Guillermo) Cotter, P.A. (Peggy A.) Heininger, U. (Ulrich) Camilli, A. (Andrew) Akerley, B.J. (Brian J.) Mekalanos, J.J. (John J.) Miller, J.F. (Jeff F.) Bacterial Proteins genetics Bordetella pertussis pathogenicity Transcription factors genetics Whooping cough etiology 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. 2013-07-19T08:53:32Z 2013-07-19T08:53:32Z 1998 info:eu-repo/semantics/article https://hdl.handle.net/10171/29517 eng info:eu-repo/semantics/openAccess application/pdf American Society for Microbiology |
spellingShingle | Bacterial Proteins genetics Bordetella pertussis pathogenicity Transcription factors genetics Whooping cough etiology Martinez-de-Tejada, G. (Guillermo) Cotter, P.A. (Peggy A.) Heininger, U. (Ulrich) Camilli, A. (Andrew) Akerley, B.J. (Brian J.) Mekalanos, J.J. (John J.) Miller, J.F. (Jeff F.) Neither the Bvg- phase nor the vrg6 locus of Bordetella pertussis is required for respiratory infection in mice |
title | Neither the Bvg- phase nor the vrg6 locus of Bordetella pertussis is required for respiratory infection in mice |
title_full | Neither the Bvg- phase nor the vrg6 locus of Bordetella pertussis is required for respiratory infection in mice |
title_fullStr | Neither the Bvg- phase nor the vrg6 locus of Bordetella pertussis is required for respiratory infection in mice |
title_full_unstemmed | Neither the Bvg- phase nor the vrg6 locus of Bordetella pertussis is required for respiratory infection in mice |
title_short | Neither the Bvg- phase nor the vrg6 locus of Bordetella pertussis is required for respiratory infection in mice |
title_sort | neither the bvg- phase nor the vrg6 locus of bordetella pertussis is required for respiratory infection in mice |
topic | Bacterial Proteins genetics Bordetella pertussis pathogenicity Transcription factors genetics Whooping cough etiology |
url | https://hdl.handle.net/10171/29517 |
work_keys_str_mv | AT martinezdetejadagguillermo neitherthebvgphasenorthevrg6locusofbordetellapertussisisrequiredforrespiratoryinfectioninmice AT cotterpapeggya neitherthebvgphasenorthevrg6locusofbordetellapertussisisrequiredforrespiratoryinfectioninmice AT heiningeruulrich neitherthebvgphasenorthevrg6locusofbordetellapertussisisrequiredforrespiratoryinfectioninmice AT camilliaandrew neitherthebvgphasenorthevrg6locusofbordetellapertussisisrequiredforrespiratoryinfectioninmice AT akerleybjbrianj neitherthebvgphasenorthevrg6locusofbordetellapertussisisrequiredforrespiratoryinfectioninmice AT mekalanosjjjohnj neitherthebvgphasenorthevrg6locusofbordetellapertussisisrequiredforrespiratoryinfectioninmice AT millerjfjefff neitherthebvgphasenorthevrg6locusofbordetellapertussisisrequiredforrespiratoryinfectioninmice |