PapB paralogues and their effect on the phase variation of type 1 fimbriae in Escherichia coli.
Recent work has demonstrated that expression of type 1 fimbriae is repressed by PapB, a regulator of pyelonephritis-associated pili (P-pili). PapB belongs to family of related adhesin regulators, for which consensus residues required for DNA binding and oligomerization have been identified. Of the regulators tested in this study, PapB, SfaB (S-fimbriae) and PefB (Salmonella enterica serovar Typhimurium--plasmid-encoded fimbriae) repressed FimB-promoted off-to-on inversion of the fim switch, although complete repression was 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-off inversion. Deletion analysis demonstrated that this specificity resides in 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 Gln) within the carboxy terminal virtually abolished cross-talk activity. 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 fim switch. Thus, repression of fim expression appears unique to PapB and SfaB within E. coli and requires DNA binding involving amino acid residues located both within the homologous core and in the heterogeneous carboxy terminus. The variation in the carboxy terminus between the PapB family members explains their differential effects on fim. This mechanism of cross-talk seems 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.
Holden
N J
NJ
ZAP Research Laboratory, Medical Microbiology, University of Edinburgh, Edinburgh, UK.
Uhlin
B E
BE
Gally
D L
DL
D018830:Adhesins, Escherichia coli / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D004247:DNA / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology; D029968:Escherichia coli Proteins / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000235:genetics* / Q000378:metabolism*; D014644:Genetic Variation; D019426:Integrases / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011995:Recombination, Genetic; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D018830:Adhesins, Escherichia coli; D017931:DNA Primers; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; C116245:atpD protein, E coli; C081956:fimB protein, E coli; D004247:DNA; D019426:Integrases