PapB paralogues and their effect on the phase variation of type 1 fimbriaein Escherichia coli

Recent work has demonstrated that expression of type 1 fimbriae is represse d by PapB, a regulator of pyelonephritis-associated pili (P-pili). PapB bel ongs to family of related adhesin regulators, for which consensus residues required for DNA binding and oligomerization have been identified. Of the r egulators tested in this study, PapB, SfaB (S-fimbriae) and PefB (Salmonell a enterica serovar Typhimurium plasmid-encoded fimbriae) repressed FimB-pro moted off-to-on inversion of the fim switch, although complete repression w as only demonstrated by PapB. DaaA, FaeB, FanA, FanB and ClpB had no effect on fim switching. In addition, only PapB stimulated FimE-promoted on-to-of f inversion. Deletion analysis demonstrated that this specificity resides i n the carboxy terminal of the protein, and not the amino terminal, with the central region being homologous among the family members. Exchange of Leu( 82) and Ile(83) of PapB for the equivalent residues from the DaaA protein ( Phe and Gin) within the carboxy terminal virtually abolished cross-talk act ivity. Whereas PapB can bind to a region around the left inverted repeat of the fim switch, DaaA and the PapB double mutant were effectively unable to bind this region. A previously characterized PapB DNA binding mutant also failed to bind to this region and failed to inhibit FimB activity at the fi m switch. Thus, repression of fim expression appears unique to PapB and Sfa B within E. coli and requires DNA binding involving amino acid residues loc ated both within the homologous core and in the heterogeneous carboxy termi nus. The variation in the carboxy terminus between the PapB family members explains their differential effects on fim. This mechanism of cross-talk se ems restricted to the P and S family adhesins with type 1 fimbriae and may ensure variable and sequential expression of adhesins during urinary tract infections.