title: Receptor mimicry as novel therapeutic treatment for biothreat agents.
abstract: The specter of intentional release of pathogenic microbes and their toxins is a real threat. This article reviews the literature on adhesins of biothreat agents, their interactions with oligosaccharides and the potential for anti-adhesion compounds as an alternative to conventional therapeutics. The minimal binding structure of ricin has been well characterised and offers the best candidate for successful anti-adhesion therapy based on the Galβ1-4GlcNAc structure. The botulinum toxin serotypes A-F bind to a low number of gangliosides (GT1b, GQ1b, GD1a and GD1b) hence it should be possible to determine the minimal structure for binding. The minimal disaccharide sequence of GalNAcβ1-4Gal found in the gangliosides asialo-GM1 and asialo-GM2 is required for adhesion for many respiratory pathogens. Although a number of adhesins have been identified in bacterial biothreat agents such as Yersinia pestis, Bacillus anthracis, Francisella tularensis, Brucella species and Burkholderia pseudomallei, specific information regarding their in vivo expression during pneumonic infection is lacking. Limited oligosaccharide inhibition studies indicate the potential of GalNAcβ1-4Gal, GalNAcβ-3Gal and the hydrophobic compound, para-nitrophenol as starting points for the rational design of generic anti-adhesion compounds. A cocktail of multivalent oligosaccharides based on the minimal binding structures of identified adhesins would offer the best candidates for anti-adhesion therapy.
authors.affiliation: Biomedical Sciences, Dstl Porton Down, Salisbury, Wiltshire UK. rjthomas@dstl.gov.uk
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Thomas
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000187:drug effects* / Q000633:toxicity; D000818:Animals; D057005:Bioengineering; D023482:Bioterrorism / Q000517:prevention & control*; D002240:Carbohydrate Sequence; D015195:Drug Design; D006801:Humans; D018716:Molecular Mimicry; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000187:drug effects; D012137:Respiratory System / Q000737:chemistry / Q000187:drug effects / Q000382:microbiology; D014118:Toxins, Biological / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D018829:Adhesins, Bacterial; D009844:Oligosaccharides; D011971:Receptors, Immunologic; D014118:Toxins, Biological; C047105:bacterial adhesin receptor