Parasites' Achilles Heel
A large proportion of the multicellular parasites from which humanity suffers have special cell bodies that are equipped with their own genetic material. In Petri dishes, antibiotics were used to inhibit their reproduction, which ultimately even killed the parasites. If the drugs are also effective in animal and human experiments, a powerful new weapon in the fight against parasites would be available. In Nature (November 27), scientists report that antibiotics designed to kill bacteria in petri dishes can also delay the growth of a multicellular parasite. Apparently they prevent the DNA from being replicated in the apicoplast, a mysterious organellum in the parasites. Apicoplasts are found in thousands of different parasites, from the pathogen causing malaria to the germs that kill AIDS patients. Therefore, experts believe drugs can be developed that could target a wide range of parasites.
As early as the 1960s, parasitologists discovered apicoplasts in various parasites. But just this year, David Roos and his colleagues at the University of Pennsylvania in Philadelphia confirmed that this structure has its own genes and could therefore be important for the parasite organism. However, they knew next to nothing about the function of the apicoplast. So they weren't sure if it's more of a vital organ of the parasite or, as Roos puts it, more like an appendix: kind of interesting, but not particularly useful. If an apicoplast were necessary for survival, one could appropriate drug might kill the parasite while sparing the host cells lacking apicoplasts.
Roos and his colleague Maria Fichers investigated this possible Achilles heel. They assumed that a suitable antibiotic would stop the reproduction of the apicoplast DNA because the apicoplast has circular DNA - as is common in bacteria. The researchers treated human connective tissue cells in a petri dish infected with Toxoplasma gondii, a parasite that causes the deadly toxoplasmosis in AIDS patients. The antibiotic ciprofloxacin not only inhibited the replication of the apicoplast DNA by 50%, it also made the parasite reproduce three times slower and then killed it.
The drug is still not on its way to pharmacies because other experiments have shown that it is unable to kill parasites in infected animals. However, Roos hopes that the substance will prove to be more effective after minor changes. Even if a ciprofloxacin derivative doesn't completely stop infection in humans or animals, "we may be able to slow it down enough that another drug could be used to effectively combat it," says Naomi Lang-Unnasch, a molecular biologist from the University of Alabama at Birmingham. What's really interesting, she says, is that a single drug may be enough to kill dozens of the more than 5,000 apicoplast parasites.
