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Evidence for phenotypic bistability resulting from transcriptional interference of bvgAS in B ordetella bronchiseptica
Author(s) -
Mason Eliza,
Henderson Michael W.,
Scheller Erich V.,
Byrd Matthew S.,
Cotter Peggy A.
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12394
Subject(s) - biology , mutant , bordetella bronchiseptica , mutation , phenotype , gene , microbiology and biotechnology , operon , genetics , bacteria
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.