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Review

Receptor mimicry as novel therapeutic treatment for biothreat agents

Richard J. Thomas

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The spectre 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

Richard J. Thomas Corresponding author: rjthomas@dstl.gov.uk

This is an open-access article

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