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A structural study of the interaction between the Dr haemagglutinin DraE and derivatives of chloramphenicol.

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Pettigrew DM, Roversi P, Davies SG, Russell AJ, Lea SM
OpenAccess logo Acta Crystallogr D Biol Crystallogr 65 513-22 (2009)
Related entries: 2jkj, 2jkl, 2jkn

Cited: 8 times
EuropePMC logo PMID: 19465765

Abstract

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.

Articles - 2w5p mentioned but not cited (2)

  1. A structural study of the interaction between the Dr haemagglutinin DraE and derivatives of chloramphenicol. Pettigrew DM, Roversi P, Davies SG, Russell AJ, Lea SM. Acta Crystallogr D Biol Crystallogr 65 513-522 (2009)
  2. Tailoring pore distribution in polymer films via evaporation induced phase separation. Pervin R, Ghosh P, Basavaraj MG. RSC Adv 9 15593-15605 (2019)


Reviews citing this publication (3)

  1. Adhesive organelles of Gram-negative pathogens assembled with the classical chaperone/usher machinery: structure and function from a clinical standpoint. Zav'yalov V, Zavialov A, Zav'yalova G, Korpela T. FEMS Microbiol Rev 34 317-378 (2010)
  2. Pathogenesis of human diffusely adhering Escherichia coli expressing Afa/Dr adhesins (Afa/Dr DAEC): current insights and future challenges. Servin AL. Clin Microbiol Rev 27 823-869 (2014)
  3. The Effect of Recombinant Human Erythropoietin on Bacterial Growth: A Dual-Edged Sword. Mittal A, Singh V, Chowdhary S, Moideen A, Kumar D, Maniar K, Bhattacharyya R, Banerjee D. Kidney Dis (Basel) 5 81-90 (2019)

Articles citing this publication (3)

  1. A shear stress micromodel of urinary tract infection by the Escherichia coli producing Dr adhesin. Zalewska-Piątek B, Olszewski M, Lipniacki T, Błoński S, Wieczór M, Bruździak P, Skwarska A, Nowicki B, Nowicki S, Piątek R. PLoS Pathog 16 e1008247 (2020)
  2. Biochemical characteristic of biofilm of uropathogenic Escherichia coli Dr(+) strains. Zalewska-Piątek B, Wilkanowicz S, Bruździak P, Piątek R, Kur J. Microbiol Res 168 367-378 (2013)
  3. Role of Src kinases in mobilization of glycosylphosphatidylinositol-anchored decay-accelerating factor by Dr fimbria-positive adhering bacteria. Queval CJ, Nicolas V, Beau I. Infect Immun 79 2519-2534 (2011)


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