Analysis of he complete genome sequence of
Unlike many parasitic diseases, cryptosporidiosis is not just limited to the developing world—it is a global problem. In 1993, a major outbreak in Milwaukee infected more than 400,000 people, including about half of Milwaukee's residents with AIDS, nearly 70% of whom died within 6 months.
The ability of cryptosporidiosis to cause such massive outbreaks and its resistance to standard water treatment regimens have caused concern over the potential use of
The genome provides the basis for understanding the mechanisms by which the organism causes disease and what causes the differences in virulence and host specificity displayed by different isolates. Abrahamsen hopes that it will point the way to effective drug targets. “This analysis has identified several biochemical pathways with specific enzymes that appear to be more similar to plants and bacteria than the mammalian versions, providing a wide range of new therapeutic targets,” he told The Scientist.
Now that the entire sequence is available, studies can begin the comparison of molecular drug targets and many aspects of the biology of cryptosporidia with other related species, such as
The most striking difference between
“In retrospect, if you look at the targets that are usually hit in these apicomplexan parasites, either the target enzyme is plainly not there in
To Striepen, the most important finding from the genome sequence is how streamlined its metabolism is. “Biosynthesis is reduced to practically nothing… They completely depend on salvage for most of the molecules they use,” he said. This should make them vulnerable to drugs that destroy the parasites' scavenging systems, and Striepen is currently working to disable the enzymes that import nucleotides into the organism.
“Now we have a new list of targets to test. We are no longer blindfolded—our efforts can be much more directed and can focus on metabolically appropriate targets,” Striepen said.
Editor's note: See a letter on this story.