UNIQUE ENZYME TARGETS FOR GONOCOCCAL ANTIMETABOLITES

Award Information
Agency: Department of Defense
Branch: Army
Contract: N/A
Agency Tracking Number: 15104
Amount: $50,000.00
Phase: Phase I
Program: SBIR
Awards Year: 1991
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
Progress Center One Progress, Blvd Box 26, Alachua, FL, 32615
DUNS: N/A
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 Dr Randy S Fischer
 Principal Investigator
 (904) 462-3904
Business Contact
Phone: () -
Research Institution
N/A
Abstract
THE ABILITY OF NEISSERIA GONORRNOEAE TO METABOLIZE LACTATE DERIVED FROM HOST NEUTROPHILS HAS BEEN IMPIICITED IN A PATHOGENIC MECHANISM THAT FAVORS OXYGEN CONSUMPTION BY GONOCOCCI AND REDUCES THE ABILITY OF PHAGOCYTES TO PRODUCE SUPEROXIDE. A MEMBRANE-BOUND LACTATE DEHYDROGENASE (ILDH) AND SOLUBLE LACTATE DEHYDROGENASE (NLDH) PARTICIPATE IN LACTATE METABOLISM. SINGLE AND DOUBLE MUTANTS WILL BE USED TO ASSESS THE EFFECTS OF INHIBITORS OF ILDH AND/OR NLDH UPON GROWTH PHYSIOLOGY AND ENERGY METABOLISM. FEASIBILITY DEMONSTRATED BY THIS APPROACH WILL PROVIDE A RATIONALE FOR STRATEGIES TO ELUCIDATE THE GENE-ENZYME RELATIONSHIPS OF THIS SYSTEM TO ENHANCE INSIGHT INTO THE NATURE OF THE HOST-PATHOGEN INTERACTION. THE GENE SEQUENCES SHOULD, IN TURN, PROVIDE A MOLECULAR-GENETIC BASIS FOR EVENTUAL ATTEMPTS TO ABOLISH SELECTIVELY THE EXPRESSION OF THESE GENES. BY THE END OF THE PROPOSED GRANT PERIOD IT IS ANTICIPATED THAT A STRONG BASIS OF FEASIBILITY WILL BE ESTABLISHED (I) FOR DESIGN OF SELECTIVE INHIBITORS ACTING AT THE ENZYME LEVEL, (II) FOR DESIGN OF SELECTIVE ANTISENSE INHIBITORS ACTING AT THE LEVEL OF MRNA, AND (III) TO DEMONSTRATE DIRECTLY THE UTILITY OF THESE AS TOOLS TO DISRUPT THE PATHOGENIC STATE IN THE MOST APT MODEL SYSTEMS AVAILABLE.

* Information listed above is at the time of submission. *

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