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Bacterial
Adhesion |
Lea Group
Lea Group |
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 Bacterial adhesins are important virulence factors
that allow colonisation of the human urogenital tract by Eschericia
coli.
The observation that many E. coli would haemagluttinate human
erythrocytes
led eventually to the realisation that a large number of these adhesins
recognised
and bound to CD55
. These so-called Dr haemagluttinins include the fimbrial Dr, X and
diarrhoea-associated
F1845 adhesins and the afimbrial Afa adhesins. This family of molecules
share
a common genetic organisation and have similar nucleotide sequences but
detailed analysis of the interaction determinants shows that they are
dependent on
different portions of CD55 for recognition and binding. In a
collaoration
with Prof. S. Matthews (Imperial College, London) we have solved NMR
and
X-ray structures of Afa and Dr adhesins in monomeric and trimeric forms
and
studied the interactions of these wtih CD55 using SPR and chemical
shift
mapping. Chloramphenicol has been previously identified as disrupting
the
CD55-adhesin interaction and we have therefore also solved the
structure
of a complex between the drug and the Dr adhesin. This structure
reveals
that the chloramphenicol binds in a surface pocket at the centre of the
CD55
binding site. Future studies will aim to study the interactions with
collagen
and CD55 using X-ray crystallography. |
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High resolution studies of the Afa/Dr adhesin DraE and
its interaction with
chloramphenicol |
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An atomic resolution model for assembly, architecture,
and function of the
Dr adhesins. |