Evaluation of the Role of the Bvg Intermediate Phase in Bordetella pertussis during Experimental Respiratory Infection
2005
Vergara-Irigaray, Nuria | Chávarri-Martínez, Alberto | Rodríguez-Cuesta, Juan | Miller, Jeff F. | Cotter, Peggy A. | Martínez de Tejada, Guillermo
The BvgAS system of Bordetella pertussis was traditionally considered to mediate a transition between two phenotypic phases (Bvg⁺ and Bvg⁻) in response to environmental signals. We characterized a third state, the intermediate (Bvg[superscript i]) phase, which can be induced by introducing a 1-bp substitution into bvgS (the bvgS-I1 mutation) or by growing B. pertussis under conditions intermediate between those leading to the Bvg⁺ and Bvg⁻ phases. Like B. bronchiseptica, B. pertussis displays in its Bvg[superscript i] phase a characteristic colony morphology and hemolytic activity and expresses a Bvg[superscript i]-phase-specific polypeptide called BipA, whose synthesis is regulated by bvgAS at the transcriptional level. Based on our results, we hypothesize that the Bvg[superscript i] phase of B. pertussis may be involved in facilitating transmission between hosts. Thus, a B. pertussis mutant carrying the bvgS-I1 mutation (GMT1i) persisted at wild-type levels only in the upper murine respiratory tract. Interestingly, a bipA deletion derivative of GMT1i displayed a reduced ability to colonize the nasal cavity of mice compared with GMT1i. However, in experimental mixed infections GMT1i expressing the Bvg[superscript i] phase could establish an initial colonization in the nose and trachea of mice as efficiently as GMT1, but the wild-type strain outcompeted GMT1i at a later time point at all sites of the respiratory tract, suggesting that the Bvg[superscript i] phase does not serve as a phenotypic phase specialized in colonization. Finally, even though B. pertussis expresses in vitro the Bvg[superscript i] phase at the human nasal temperature, anti-BipA antibodies were undetectable in a large collection of sera from pertussis patients.
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