Evidence for phenotypic bistability resulting from transcriptional interference of bvgAS in Bordetella bronchiseptica.

Evidence for phenotypic bistability resulting from transcriptional interference of bvgAS in Bordetella bronchiseptica.
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DOI:
10.1111/mmi.12394
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发表时间:
2013-11
影响因子:
3.6
通讯作者:
Cotter PA
Cotter PA
中科院分区:
生物学2区
文献类型:
--
作者:
Mason E;Henderson MW;Scheller EV;Byrd MS;Cotter PA

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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 hemagglutinin. 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.
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