The bacteria that cause Legionnaires’ disease and Q fever, both of which are linked to pneumonia, use a clever form of mimicry to survive inside host cells, according to a team of Yale scientists. Both bacteria use genes that have evolved in tandem with genes in their hosts and that disarm the immune system cells that are trying to kill them, the researchers reported in the journal Science in June.
“Because of their lifestyle, trying to identify how these organisms cause disease has been really difficult,” said Craig R. Roy, Ph.D., associate professor of microbial pathogenesis, referring to the fact that the bacteria live inside their host cells. Roy’s team knew that some disease-causing bacteria inject proteins into human cells. What those proteins are and what they do, though, was unknown.
Previous research on the genomes of the bacteria, Legionella and Coxiella, had turned up many genes with areas called ANKs (ankyrin repeat homology domains). These genes bear a strong resemblance to important genes in eukaryotic cells, those cells with a nucleus that are found in humans and other advanced life forms. Legionella and Coxiella appear to have “hijacked” genes from their hosts in order to survive in the cell. In fact, some species of these bacteria cannot exist outside a eukaryotic cell.
Roy’s lab showed that ANK proteins are secreted into macrophages—immune system cells—and once inside, the proteins turn off mechanisms designed to destroy the bacteria. The macrophage ordinarily kills bacteria by exposing them to a destructive acidic environment, but the ANK proteins prevent the acidic compartment from being transported to the bacteria by mimicking a natural process that occurs during cell division.
Roy believes that more such survival tricks of gram-negative pathogens will be found, and that the diseases may one day be preventable with a vaccine that disables the ANK protein and allows macrophages to complete the job of destruction. “This study at least gives us a foothold,” he said.