Abstract
The whooping cough agent Bordetella pertussis coordinately regulates the expression of its virulence factors with the two-component system BvgAS. In laboratory conditions, specific chemical modulators are used to trigger phenotypic modulation of B. pertussis from its default virulent Bvg+ phase to avirulent Bvg- or intermediate Bvgi phases, in which no virulence factors or only a subset of them are produced, respectively. Whether phenotypic modulation occurs in the host remains unknown. In this work, recombinant B. pertussis strains harboring BvgS variants were tested in a mouse model of infection and analyzed using transcriptomic approaches. Recombinant BP-BvgΔ65, which is in the Bvgi phase by default and can be up-modulated to the Bvg+ phase in vitro, could colonize the mouse nose but was rapidly cleared from the lungs, while Bvg+-phase strains colonized both organs for up to four weeks. These results indicated that phenotypic modulation, which might have restored the full virulence capability of BP-BvgΔ65, does not occur in mice or is temporally or spatially restricted and has no effect in those conditions. Transcriptomic analyses of this and other recombinant Bvgi and Bvg+-phase strains revealed that two distinct ranges of virulence gene expression allow colonization of the mouse nose and lungs, respectively. We also showed that a recombinant strain expressing moderately lower levels of the virulence genes than its wild type parent was as efficient at colonizing both organs. Altogether, genetic modifications of BvgS generate a range of phenotypic phases, which are useful tools to decipher host-pathogen interactions.
Highlights
Bordetella pertussis is the agent of an acute respiratory disease, whooping cough
The recombinant B. pertussis strains were obtained by introducing the pBBRmpla variant by conjugation in B. pertussis BPSMnewΔAS carrying the chromosomal ptx-lacZ transcriptional fusion [12]. bvgSΔ65 was cloned on a plasmid in a similar manner for comparison
Those results indicate that the default state of BP-BvgSΔ65 is the Bvgi phase
Summary
Bordetella pertussis is the agent of an acute respiratory disease, whooping cough. Despite the current global vaccination coverage of approximately 86% of the population, this bacterium. Virulence phenotypes of Bordetella pertussis with BvgS variants laboratory (Inserm, Lille University). E. L. received a fellowship form the Region Nord-Pas-de-Calais and Inserm. The authors thank the UMR 8199 LIGAN-PM Genomics platform (Lille, France) which belongs to the ’Federation de Recherche’ 3508 Labex EGID (European Genomics Institute for Diabetes; ANR-10-LABX-46) and was supported by the ANR Equipex 2010 session (ANR-10-EQPX-0701; ’LIGAN-PM’). The LIGAN-PM Genomics platform (Lille, France) is supported by the FEDER and the Region Nord-Pas-de-CalaisPicardie. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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