title: Evidence for phenotypic bistability resulting from transcriptional interference of bvgAS in Bordetella bronchiseptica.
abstract: Bordetella species cause respiratory infections in mammals. Their master regulatory system BvgAS controls expression of at least three distinct phenotypic phases in response to environmental cues. The Bvg⁺ phase is necessary and sufficient for respiratory infection while the Bvg⁻ phase is required for survival ex vivo. We obtained large colony variants (LCVs) from the lungs of mice infected with B. bronchiseptica strain RBX9, which contains an in-frame deletion mutation in fhaB, encoding filamentous haemagglutinin. RBX9 also yielded LCVs when switched from Bvg⁻ phase conditions to Bvg⁺ phase conditions in vitro. We determined that LCVs are composed of both Bvg⁺ and Bvg⁻ phase bacteria and that they result from defective bvgAS positive autoregulation. The LCV phenotype was linked to the presence of a divergent promoter 5' to bvgAS, suggesting a previously undescribed mechanism of transcriptional interference that, in this case, leads to feedback-based bistability (FBM). Our results also indicate that a small proportion of RBX9 bacteria modulates to the Bvg⁻ phase in vivo. In addition to providing insight into transcriptional interference and FBM, our data provide an example of an in-frame deletion mutation exerting a 'polar' effect on nearby genes.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599-7290, USA.
authors.forename: Eliza
authors.initials: E
authors.lastname: Mason
authors.forename: Michael W
authors.initials: MW
authors.lastname: Henderson
authors.forename: Erich V
authors.initials: EV
authors.lastname: Scheller
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Byrd
authors.forename: Peggy A
authors.initials: PA
authors.lastname: Cotter
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001885:Bordetella Infections / Q000382:microbiology*; D016950:Bordetella bronchiseptica / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008168:Lung / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D012141:Respiratory Tract Infections / Q000382:microbiology*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D010566:Virulence Factors, Bordetella / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C065601:BvgA protein, Bacteria; D014157:Transcription Factors; D010566:Virulence Factors, Bordetella