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Dr adhesins are expressed on the surface of uropathogenic and diffusely adherent strains of Escherichia coli. The major adhesin subunit (DraE/AfaE) of these organelles mediates attachment of the bacterium to the surface of the host cell and possibly intracellular invasion through its recognition of the complement regulator decay-accelerating factor (DAF) and/or members of the carcinoembryonic antigen (CEA) family. The adhesin subunit of the Dr haemagglutinin, a Dr-family member, additionally binds type IV collagen and is inhibited in all its receptor interactions by the antibiotic chloramphenicol (CLM). In this study, previous structural work is built upon by reporting the X-ray structures of DraE bound to two chloramphenicol derivatives: chloramphenicol succinate (CLS) and bromamphenicol (BRM). The CLS structure demonstrates that acylation of the 3-hydroxyl group of CLM with succinyl does not significantly perturb the mode of binding, while the BRM structure implies that the binding pocket is able to accommodate bulkier substituents on the N-acyl group. It is concluded that modifications of the 3-hydroxyl group would generate a potent Dr haemagglutinin inhibitor that would not cause the toxic side effects that are associated with the normal bacteriostatic activity of CLM.

Original publication

DOI

10.1107/S0907444909005113

Type

Journal article

Journal

Acta Crystallogr D Biol Crystallogr

Publication Date

06/2009

Volume

65

Pages

513 - 522

Keywords

Acylation, Adhesins, Escherichia coli, Anti-Bacterial Agents, Bacterial Adhesion, Binding Sites, CD55 Antigens, Carcinoembryonic Antigen, Chloramphenicol, Collagen Type IV, Crystallization, Crystallography, X-Ray, Escherichia coli, Escherichia coli Infections, Hydroxyl Radical, Kidney, Models, Chemical, Protein Binding, Protein Conformation, Virulence, Virulence Factors