Thanks to decades of herbicide research, the pathway is already well studied and several inhibitory compounds are available. The researchers have also begun looking for compounds that affect other enzymes and substrates in the pathway in novel ways.
In addition to the seven skikimate-pathway enzymes, these findings suggest that the enzymes responsible for other biochemical pathways which branch from the shikimate pathway, as well as other plant-like metabolic pathways, could also become drug targets.
Medications that target the shikimate pathway may also prove valuable against other disease-causing bacteria or fungi that rely on the pathway, such as Mycobacterium tuberculosis, which causes tuberculosis, Staphylococcus aureus, a common and increasingly drug-resistant cause of serious post-operative infections, and Pneumocystis carinii, the most frequent cause of pneumonia in patients with AIDS.
"Despite 50 years of intense research into anti-microbials, rationally selecting plant-like metabolic pathways to identify targets in Apicomplexans has not been tried previously," commented McLeod. Her team sought targets that were part of interelated metabolic pathways present in lower species but not present or very different in humans, a novel paradigm for rational drug discovery.
"The urgent need for better medications combined with recent recognition of similarities of Apicomplexan parasites and plants provided the rationale for the initial experiments," she added, "followed by multi-institutional collaborations of infectious disease specialists, parasitologists, biochemists, plant molecular biologists, and John Coggins, Ph.D., of Glasgow University, one of the world's experts in the shikimate pathway."
Additional authors of the paper include co-first authors Fiona Roberts, M.D.,
and Craig Roberts, M.D., who
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Contact: John Easton
jeaston@mcis.bsd.uchicago.edu
773 702 6241
University of Chicago Medical Center
25-Jun-1998