Methods of identifying bacterial genes that are in

专利名称：Methods of identifying bacterial genes that

are incompatible with bacterial

pathogenicity, and the use of such genes,such as cadA, to reduce pathogenicity in abacteria or to combat pathogenic bacterialinfections

发明人：Anthony T. Maurelli,Reinaldo E.

Fernández,Craig A. Bloch,Alessio Fasano

申请号：US09281274申请日：19990330公开号：US06344201B1公开日：20020205

摘要：“Black holes” in the genomes of bacterial pathogens represent deletions of“anti-virulence” genes, i.e. genes that are detrimental to a pathogenic lifestyle.Identification of the missing genetic loci in the “black hole” identifies genes that areincompatible with the bacteria's pathogenicity. These genes, their gene products, andcompounds generated by the enzymatic action of these gene products representpotential new compounds that are inhibitory to the bacterial pathogen and thus useful aspharmaceuticals. The utility of this concept is demonstrated in the missing gene for lysinedecarboxylase, and the resulting inhibitory activity of cadaverine (the diaminoalkylreaction product of lysine decarboxylase) on the Shigella enterotoxins. Diaminoalkylcompounds are therefore potent inhibitors of and Shigella spp. enterotoxins. Lysinedecarboxylase generated from the gene cadA results in attenuation of the enterotoxic

effects. New methods of use of diaminoalkyl compounds as medicaments are described.New uses of genetic constructs containing a cadA sequence, or other “anti-virulence”gene, for biochemical probes, for toxin receptor identification, and for pharmaceuticaldiscovery are described. Additional uses are described for vaccines and DNA vaccinedelivery.

申请人：MAURELLI ANTHONY T.,FERNÁNDEZ REINALDO E.,BLOCH CRAIGA.,FASANO ALESSIO

代理机构：Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P.

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