Novel Neisseria Gonorrhoeae Therapeutic Based on CMP-Nonulosonate Sugars
AssigneesNational Research Council of Canada, University of Massachusetts Medical School
InventorsIan SCHOENHOFEN, Dennis M. WHITFIELD, Sanjay RAM
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Abstract
N. gonorrhoeae has become resistant to almost every conventional antibiotic. Described herein is the use of CMP-nonulosonate analogues to counter gonococcal complement evasion. The nonulosonate sugar is incorporated into the lipooligosaccharide of the N. gonorrhoeae which in turn reduces the serum resistance of the bacteria. This provides a novel therapeutic strategy against the global threat of multi-drug resistant gonorrhea.
Claims7
A method for modifying a molecule with N,N′-diacetyllegionaminic acid (Leg5Ac7Ac) comprising:
- contacting an acceptor molecule bearing a terminal Galβ-1,4-GlcNAc residue with an activated sugar nucleotide of N,N′-diacetyllegionaminic acid (CMP-Leg5Ac7Ac) in the presence of a sialyltransferase derived from a Neisseria spp.
A method for identifying a cytidine 5′-monophospho-nonulosonate sugar capable of reducing virulence of N. gonorrhoeae comprising:
- incubating N. gonorrhoeae with the cytidine 5′-monophospho-nonulosonate sugar of interest under conditions suitable for incorporation of nonulosonate sugar into lipooligosaccharide of the N. gonorrhoeae;
- and
- determining if serum resistance of the N. gonorrhoeae is reduced compared to an untreated control culture of N. gonorrhoeae.
Dependencies are inferred from the claim text.