Fimbrial phase variation in Bordetella pertussis: a novel mechanism for transcriptional regulation.

Abstract

Fimbriae belong to a class of extracellular filamentous proteins which are involved in the attachment of bacteria to host tissues. Bordetella pertussis, the etiological agent of whooping cough, produces two serologically distinct fimbriae. We show that, like a number of other B. pertussis virulence genes, transcription of the fimbrial subunit genes (fim) is positively controlled by trans‐acting polypeptides encoded by the bvg locus. In addition to this coordinate control, transcription of the fim genes is regulated at an individual level by phase variation. This process is characterized by a switching between a high and low level of expression of a particular fim gene. We have identified a conserved DNA region, located close to the start of the fim genes, which is likely to be involved in both positive regulation by the bvg locus, and phase variation. This promoter region contains a stretch of approximately 15 C residues and it appears that phase transitions occur by small insertions or deletions in this C‐rich region. We propose that these mutations affect transcription of the fim genes by varying the distance between the binding site for an activator and the −10 box. The fim promoter shows homology with the pertussis toxin promoter, which is also positively regulated by the bvg locus.

Role of (p)ppGpp in biofilm formation and expression of filamentous structures in Bordetella pertussis

“…B. pertussis can produce two serologically different fimbria -Fim2 and Fim3 (Ashworth et al, 1982;Zhang et al, 1985). Transcription of fim2 and of fim3, which each encode different fimbrial subunits, is regulated by phase variation; mutations in the C-stretch, a C-rich region of each promoter (fim2 and fim3), cause on/off switching that leads to phase variation (Willems et al, 1990). The wild-type strain used in this study expresses only Fim3-type fimbriae.…”

The Bordetella pertussis model of exquisite gene control by the global transcription factor BvgA

“…Consistent with this idea is the effect of different lengths of homopolymeric tracts in the promoter regions of the fim genes, described below. Changing the lengths of these promoter regions, which alters the spacing between promoter elements as well as relative orientation of one bound protein to another around the double-helix, has dramatic effects on promoter activity (Chen et al, 2010;Riboli et al, 1991;Willems et al, 1990).…”

“…Expression of the fim genes is regulated at multiple levelsas part of the BvgAS regulon and at the level of the individual gene through phase variation (Heikkinen et al, 2008;Willems et al, 1990). Phase variation is a phenomenon that allows expression of a given factor to switch between 'on' or 'off' states at a rate greater than that of random mutation, frequently affecting fimbriae, flagella, outer-membrane proteins and lipopolysaccharide components in Gram-negative bacteria (reviewed by Dybvig, 1993;Henderson et al, 1999).…”

“…4) (Chen et al, 2010;Willems et al, 1990). This tract does not contain sequence-specific information, but instead appears to function as a spacer between transcription activation machinery bound to different elements of the promoter (Chen et al, 2010).…”

“…Interestingly, a B. pertussis gene with sequence homology to fim3 and fim2 has an extremely truncated promoter Ctract: 7 Cs compared with 15 Cs in the active form of fim3. This gene, called fimX, appears to be transcriptionally silent due to the deletion in the C-tract (Chen et al, 2010;Willems et al, 1990). Moreover, the shorter homopolymeric tract limits the amount of slipped-strand mispairing that is likely to occur, making a reversion to activity by addition of Cs highly improbable.…”