Abstract
Immune escape is considered to be the driving force behind structural variability of major antigens on the surface of bacterial pathogens, such as fimbriae. In the Dr family of Escherichia coli adhesins, structural and adhesive functions are carried out by the same subunit. Dr adhesins have been shown to bind decay-accelerating factor (DAF), collagen IV, and carcinoembryonic antigen-related cell adhesion molecules (CEACAMs). We show that genes encoding Dr adhesins from 100 E. coli strains form eight structural groups with a high level of amino acid sequence diversity between them. However, genes comprising each group differ from each other by only a small number of point mutations. Out of 66 polymorphisms identified within the groups, only three were synonymous mutations, indicating strong positive selection for amino acid replacements. Functional analysis of intragroup variants comprising the Dr haemagglutinin (DraE) group revealed that the point mutations result in distinctly different binding phenotypes, with a tendency of increased affinity to DAF, decreased sensitivity of DAF binding to inhibition by chloramphenicol, and loss of binding capability to collagen, CEACAM3 and CEACAM6. Thus, variability by point mutation of major antigenic proteins on the bacterial surface can be a signature of selection for functional modification.
Publication types
- Research Support, N.I.H., Extramural
MeSH terms
- Adhesins, Bacterial / chemistry
- Adhesins, Bacterial / genetics
- Adhesins, Bacterial / metabolism
- Adhesins, Escherichia coli / chemistry
- Adhesins, Escherichia coli / genetics
- Adhesins, Escherichia coli / metabolism
- Amino Acid Sequence
- Bacterial Adhesion
- CD55 Antigens / metabolism
- Cell Line
- Escherichia coli / genetics
- Escherichia coli / metabolism*
- Escherichia coli / pathogenicity*
- Escherichia coli Proteins / chemistry
- Escherichia coli Proteins / genetics
- Escherichia coli Proteins / metabolism
- Evolution, Molecular
- Fimbriae, Bacterial
- Genetic Variation*
- Humans
- Molecular Sequence Data
- Point Mutation*
- Selection, Genetic*
- Surface Plasmon Resonance
Substances
- Adhesins, Bacterial
- Adhesins, Escherichia coli
- CD55 Antigens
- Dr adhesin, E coli
- DraE protein, E coli
- Escherichia coli Proteins
Associated data
- GENBANK/DQ385996
- GENBANK/DQ385997
- GENBANK/DQ385998
- GENBANK/DQ385999
- GENBANK/DQ386000
- GENBANK/DQ386001
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