Disease relevance of fimH

• Three novel fim genes of Escherichia coli, fimF, fimG and fimH, were characterized [1].
• The pilA gene of Neisseria gonorrhoeae was initially identified in a screen for transcriptional regulators of pilE, the expression locus for pilin, the major structural component of gonococcal pili [2].
• Using a pilE::lacZ transcriptional fusion, we demonstrate that the RpoN sigma factor can function in Escherichia coli to increase pilE transcription when the NifA activator from Klebsiella is present in trans [3].

High impact information on fimH

• Random point mutations in fimH genes that increase binding of the adhesin to mono-mannose residues, structures abundant in the oligosaccharide moieties of urothelial glycoproteins, confer increased virulence in the mouse urinary tract [4].
• In this study, we have analyzed in more detail the ability of isogenic, recombinant strains of E. coli expressing fimH genes of the predominant fecal and UTI phenotypes to adhere to glycoproteins and to uroepithelial cells [5].
• We have obtained nascent FimH that has not been incorporated into the fimbrial structure from the periplasm of an E. coli strain expressing the cloned fimH gene [6].
• We have analysed the variability of fimA and fimH in strains of vaginal and other origin that belong to one of the most prominent clonal groups of extraintestinal pathogenic E. coli, comprised of O1:K1-, O2:K1- and O18:K1-based serotypes [7].
• Thus, while structurally diverse pilin subunits of E. coli fimbriae are under selective pressure for frequent horizontal transfer between clones, the adhesive subunits of extraintestinal E. coli are under strong positive selection (Dn/Ds > 1 for fimH and papG) for functionally adaptive amino acid replacements [7].

Chemical compound and disease context of fimH

• Our results suggest that the fimG and fimH gene products are components of type 1 fimbriae and that FimH may be the tip adhesin mediating the binding of type 1 fimbriated E. coli to D-mannose residues on mucosal surfaces [8].
• Out of nine fimH genes analysed from isolates of E. coli, collagen adhesiveness as well as alanine at position 62 in FimH were found only in two O18acK1H7 isolates with the isoenzyme profile ET type 1 [9].

Biological context of fimH

• Representative fimH genes were sequenced, and the deduced amino acid sequences were compared with the previously published FimH sequence [10].
• The fimH genes were amplified by PCR from chromosomal DNA obtained from representative strains and expressed in a delta fim strain (AAEC191A) transformed with a recombinant plasmid containing the entire fim gene cluster but with a translational stop-linker inserted into the fimH gene (pPKL114) [10].
• No correlation was found between the fimH and fimA sequences and the following parameters: avian species, organ of isolation, serotype, presence of aerobactin receptor and virulence for chickens [11].
• Here, we have adapted two ecological analytical tools-diversity indexes D ( S ) and alpha-to compare size and frequency distributions of fimH haplotypes between evolutionarily conserved FimH variants ("source" haplotypes) and FimH variants with adaptive mutations (putative "sink" haplotypes) [12].
• The nucleotide sequence for each of the fimH genes was determined [13].

Anatomical context of fimH

• The remaining mutant, a temperature-sensitive (ts) fimH mutant that agglutinated guinea pig erythrocytes after growth at 31 degrees C but not at 42 degrees C, reacted with antiserum at both temperatures in a manner similar to the parent [14].
• Furthermore, when both strains were inoculated simultaneously, the delta fimH mutant constituted 98% of the bacterial population in the trachea at day 7 postinoculation [15].
• The PhoA hybrid proteins were shown to be located in the membrane fraction of the cells, and the prepilin product of the pilE gene was shown to be located exclusively in the cytoplasmic membrane [16].

Associations of fimH with chemical compounds

• A minor component of the pilus fiber (the product of the fimH gene, termed the adhesin) mediates attachment to a variety of host cell molecules in a mannose inhibitable interaction that has been extensively described [17].
• The deduced amino acid sequence of the N. meningitidis pilE translation product contains a 7 amino acid N-terminal pre-pilin leader sequence which is identical to that found in gonococcal pilin and which is characteristic of N-methylphenylalanine pili in general [18].

Analytical, diagnostic and therapeutic context of fimH

• Sequence analysis demonstrates the conservation of fimH and variability of fimA throughout avian pathogenic Escherichia coli (APEC) [11].
• PilA purified in this manner was used to develop a gel retardation assay with a 301-bp fragment containing the pilE promoter (PpilE) and upstream sequences as a probe [19].
• Site-directed mutagenesis of the pilE promoters followed by transcriptional analysis in E. coli indicated that in the absence of an appropriate activator protein, binding of RNA polymerase-sigma 54 to P3 inhibits transcription from P1 on the order of 30-fold [20].

References