Hybolites: Novel Therapeutic Tools for Targeting Hyperstructures in Bacteria

Guillaume      Legent; Victor      Norris

Abstract

The scarcity of new molecules that can act on bacteria is a major problem. New strategies for developing such molecules might be based on recent concepts in microbiology. Hyperstructures are large assemblies of molecules and macromolecules that perform functions such as DNA replication, RNA degradation and chemotaxis and the interactions between hyperstructures have been proposed to constitute an intermediate level of organisation in cells. Functioningdependent hyperstructures form in the presence of their substrate and dissociate in its absence. An entirely new therapy for bacterial diseases might therefore be devised based on the manipulation of hyperstructures. One way to do this would be to supply cells with hybrid metabolites or hybolites made by a pairwise, covalently linked combination of the thousands of small molecules involved in metabolism. Some of these hybolites would be substrates for two, very different, hyperstructures and might do much more than simply inhibit key enzymes and processes within the hyperstructures: they might provoke the assembly of two hyperstructures in the same space or lead to hyperstructures emitting misleading signals. It is conceivable that hybolites might even convert a pathogenic Mr Hyde into an inoffensive Dr Jekyll. The article also discusses the major patent applications of hyperstructures in bacteria.

Keywords: Functioning-dependent structure, antibiotic, degradosome, therapy, metabolite, pathogen

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