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.
Claims18
A method for identifying a cytidine 5′-monophospho-nonulosonate (CMP-nonulosonate) sugar capable of reducing virulence of N. gonorrhoeae comprising:
- incubating a control culture of N. gonorrhoeae with a first CMP-nonulosonate sugar under conditions that result in incorporation of the nonulosonate sugar of the first CMP-nonulosonate sugar into lipooligosaccharide of the N. gonorrhoeae;
- incubating a test culture of N. gonorrhoeae with the first CMP-nonulosonate sugar and a second CMP-nonulosonate sugar under conditions that result in incorporation of the nonulosonate sugar of the first CMP-nonulosonate sugar into lipooligosaccharide of the N. gonorrhoeae;
- and
- determining if serum resistance of the test culture of N. gonorrhoeae after incubation with the first and second CMP-nonulosonate sugars is Rower than serum resistance of the control culture of N. gonorrhoeae after incubation with the first CMP-nonulosonate sugar,
- wherein the first CMP-nonulosonate sugar is a CMP-nonulosonate sugar that is able to confer serum resistance to serum-sensitive N. gonorrhoeae.
A method for identifying a cytidine 5′-monophospho-nonulosonate (CMP-nonulosonate) sugar capable of reducing virulence of N. gonorrhoeae, the method comprising:
- incubating a control culture of N. gonorrhoeae with cytidine 5′-monophospho-N-glycolylneuraminic acid (CMP-Neu5Gc) under conditions that result in incorporation of the nonulosonate sugar of CMP-Neu5Gc into lipooligosaccharide of the N. gonorrhoeae;
- incubating a test culture of N. gonorrhoeae with a second CMP-nonulosonate sugar under conditions suitable for incorporation of the nonulosonate sugar of the second CMP-nonulosonate sugar into lipooligosaccharide of the N. gonorrhoeae;
- and
- determining if serum resistance of the test culture of N. gonorrhoeae after incubation with the second CMP-nonulosonate sugar is lower than serum resistance of the control culture of N. gonorrhoeae after incubation with CMP-Neu5Gc,
- wherein the control culture of N. gonorrhoeae is serum sensitive prior to incubation with the CMP-Neu5Gc, and
- wherein the test culture of N. gonorrhoeae is serum sensitive prior to incubation with the second CMP-nonulosonate sugar.
Dependencies are inferred from the claim text.