A molecular analysis of non-fimbrial adhesins in uropathogenic Escherichia coli.

Bacterial adherence is one of the most important virulence factors in the pathogenesis of urinary tract infections. The majority of clinical isolates of Escherichia coli adhere to uroepithelial cells via specific organelles known as fimbriae or pili which project from the surface. A proportion of urinary isolates possess adhesins which diffusely surround the bacteria forming an adhesive protein capsule. These are described as non-fimbrial adhesins. The molecular biology and clinical significance of this group of adhesins is relatively poorly understood. The work presented in this thesis describes the cloning and comparison of four non-fimbrial adhesins (NFA-1 to NFA-4) identified in strains of Escherichia coli isolated from patients with urinary tract infections. The NFA-2 and NFA-4 adhesin subunit gene sequences were determined. The gene complexes encoding the four non-fimbrial adhesins were of similar size and complexity. NFA-1 and NFA-2 were antigenically distinct but shared a close degree of nucleotide and amino acid homology. Comparison of NFA-1 and NFA-2 sequences with other published sequences showed that they were related to members of the Dr adhesin family. NFA-3 and NFA-4 appeared to be unrelated adhesins, however the nucleotide sequence of the NFA-4 adhesin subunit proved to be identical to the previously described M-adhesin. The clinical importance of this group of non-fimbrial adhesins was investigated by colony blotting studies. The results showed that NFA-1, NFA-2 and NFA-4 were associated with isolates causing lower urinary tract infections but NFA-3 did not appear to play an important role in urinary tract infection. The significance of the results is discussed.