Scientific Publications by FDA Staff

Mol Microbiol 2010 Sep;77(5):1326-40

Novel architectural features of Bordetella pertussis fimbrial subunit promoters and their activation by the global virulence regulator BvgA.

Chen Q, Decker KB, Boucher PE, Hinton D, Stibitz S

A prominent feature of the promoters of Bordetella pertussisfimbrial subunit genes fim2, fim3, and fimX is the presence of a "C-stretch", a monotonic run of C residues. The C-stretch renders these genes capable of phase-variation, through spontaneous variations in its length. For each of these we determined the length of the C-stretch that gave maximal transcriptional activity, and found that the three optimized promoters align perfectly, with identical distances between conserved upstream sequences and the downstream -10 elements and transcriptional start sites. We also demonstrated, for Pfim3, that the conserved sequence corresponds to BvgA-binding sites. The more upstream of the two binding sites is predicted to be high affinity, by comparison to a functionally-derived consensus BvgA-binding sequence. The other binding site is a fairly poor match to this consensus, with 10 of 14 bp belonging to the C-stretch. Interestingly, the center of this downstream site of BvgA binding coincides exactly with the center of the expected typical location of a -35 sequence. However, the lack of a recognizable -35 element (CCCCCC vs. TTGACA), and the occupation of this site by BvgA approximately P suggest that activation of the fim promoters involves unusual interactions among BvgA, RNA polymerase, and promoter DNA.