COLUMBUS , Ohio — Two wildly different pathogens — one that infects vegetables, the other infecting humans—essentially use the same protein code to get their disease-causing proteins into the cells of their respective hosts.
That’s what researchers from Ohio State and Northwestern universities report in a study published in the current issue of the journal PLoS Pathogens. The scientists were surprised to learn that the pathogen that causes malaria in humans and the microbe that caused the Irish potato famine use identical protein signals to start an infection.
"I don’t think anyone expected this," said Sophien Kamoun, a study co-author and an associate professor of plant pathology at Ohio State’s Ohio Agricultural Research and Development Center in Wooster. "These are very different pathogens, and we never realized that there might be some similarities between them."
Kamoun says not to worry — there’s no chance that the potato pathogen will jump to humans, nor is it likely that the malaria parasite will start infecting plants.
However, he said it’s feasible to think that one day researchers could develop a drug with a dual purpose — one that would stop both Plasmodium falciparum, which causes malaria, and Phytophthora infestans, the microbe that triggers late potato blight in vegetables including potatoes, soybeans and tomatoes.
"It sounds crazy, but it’s not totally ridiculous to consider such a drug," said Kamoun, who is an expert on the Phytophthora group of pathogens. He conducted the study with lead author Kasturi Haldar, of Northwestern, and with colleagues from both Ohio State and Northwestern.
Each year, malaria kills more than one million people — mostly young African children — and Phytophthora pathogens devastate a wide range of food and commercial crops.
The researchers swapped a small sequence of proteins, called the leader sequence, in P. falciparum with the leader sequence of P. infestans. A leader sequence is a group of about 20 to 30 amino acids on a protein secreted by the parasite. This sequence contains instructions on how to enter, and therefore start infecting, a plant or animal cell.
In laboratory experiments, the researchers infected human red blood cells with the modified malarial pathogen.
Results showed that malaria proteins could just as effectively enter and infect a cell when it contained the P. infestans leader sequence instead of its own.
"Our findings show that very distinct microbes can share similar strategies for delivering toxic proteins to their targets," Kamoun said.
About a year and a half ago, Kamoun and his group at Ohio State read studies conducted by the Northwestern researchers that described the leader sequence of the malaria parasite. The similarity between this and the leader sequence of P. infestans was remarkable, he said.
"So we decided to collaborate and see if the sequences were not just similar, but also functionally the same," he said. "It turned out that they were. But although the mechanism of getting virulence proteins into a host cell is very similar, the infection-causing proteins that are delivered to a host are completely different."
To Kamoun’s knowledge, this is the first paper to show that such dissimilar pathogens of this type—both are eukaryotic organisms — share a remarkably similar trait. He and his colleagues aren’t sure how to explain this phenomenon, as these pathogens belong to distinctly different evolutionary groups.
This work was supported by grants from the National Institutes of Health and by a National Science Foundation’s Plant Genome grant.
Ohio State. May 2006.