Evidence for phenotypic bistability resulting from transcriptional interference of bvgAS in B ordetella bronchiseptica

Summary B ordetella 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 B vg + phase is necessary and sufficient for respiratory infection while the B vg − 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 B vg − phase conditions to B vg + phase conditions in vitro . We determined that LCVs are composed of both B vg + and B vg − 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 B vg − 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.