Microcide Uses Novel Genomics Method To Speed Promising Antibacterial Drug Discovery.

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--Sept. 19, 1995-- Microcide, a company dedicated to developing effective drugs to treat antibiotic resistant bacterial infections, has accelerated an essential part of its drug discovery research through the novel use of a technology called genetic potentiation.

Promising results in its search for new antibacterial drug targets were presented this week by Molly Schmid, Ph.D., Microcide's associate director, biology, at the 35th Annual Interscience Conference on Antimicrobial Agents & Chemotherapy in San Francisco. Schmid discussed the effect of advances in genomics on the process of identifying new antibacterial drug targets and described the significance of Microcide's identification of "hypersensitive" mutant strains of bacteria as a powerful method for novel drug discovery.

Early work in antibacterial drug discovery at Microcide has centered around the bacteria Staphylococcus aureus. Combining molecular and genetic strategies, Microcide's scientists have searched for genes responsible for the in vivo and in vitro viability of S. aureus. These studies have led to the discovery of several functionally important genes -- some novel genes with no similar sequences yet identified in other bacteria, others sharing partial genetic sequences with several other noteworthy pathogens and well-studied bacteria, including E. coli.

Schmid explained that a key step in drug discovery at Microcide is to identify an organism's essential DNA sequences, such as those required for growth. Sequences coding for sectionary functions, such as virulence, are also relevant. Once these target regions are identified, Microcide begins screening to identify drugs that inhibit the function of the corresponding gene's product.

Microcide's unique approach to development of target-based screens is more effective than traditional biochemical screening methods, requiring less time and resource expenditure. Another benefit of genetic methods not afforded by biochemical methods is the ability to use bacterial cells to assess whether the compound can penetrate the cell. This eliminates a step in evaluating effectiveness. Using genetic potentiation, hypersensitive mutant strains are identified and then used for quick and easy screening through compound libraries.

Microcide is able immediately to sequence the pharmaceutically relevant sections of the genome, about 5 to 10 percent of the organism's total genetic material, enabling the work in multiple pathogens simultaneously. Such targets found in S. aureus may also be found in other pathogens.

Coupled with target-directed genomics, the use of "multi-channel" screening (the use of many targets simultaneously), will result in more rapid identification of larger numbers of compounds, according to Schmid. This, in turn, will lead to selection of compounds with characteristics closer to that of the final drug. Additionally, the speed of discovering new compounds should allow for more intelligent choices, alleviate some development effort and expedite the evaluation process of the potential antibacterial drugs identified. These improvements are all possible because of advanced genomics technology, and represent great potential for identifying successful therapeutic compounds in an efficient manner.

Schmid's presentation was based on studies conducted in collaboration with Dongxu Sun, Ph.D.; Patrick K. Martin, Ph.D. and Francois Malouin, Ph.D., all of Microcide. Guidance was also provided by several members of Microcide's scientific advisory board, including Sydney Brenner, Ph.D.; Patrice Courvalin, M.D.; Julian Davies, Ph.D. and Stanley Falkow, Ph.D.

Microcide Pharmaceuticals Inc. is a privately held biopharmaceutical company founded to address the emerging market created by increasing prevalence of bacterial resistance, growth of at-risk populations and decreased efforts in this arena. The company is focusing on the host-pathogen relationship and has taken a genetic approach in its technology designed to generate novel product leads. Its initial chemistry-driven efforts are aimed at discovery and development of new antibiotics for institutionally acquired bacterial infections or infections where currently available treatments are ineffective or inadequate.

CONTACT: Microcide Pharmaceuticals Inc., Mountain View

Jim Rurka, [phone]