LOUISVILLE, Ky. – Microbiologists at the University of Louisville have found that Legionella pneumophila uses a “tool” that allows it to thrive in an amoeba host and in human lung cells, but with very different results. In the amoeba, considered the bacterium’s natural host, it results in coexistence, making the amoeba host a suitable, safe home for the bacteria’s proliferation. In the human, however, it leads to a deadly form of pneumonia and a paradoxical inflammatory response in the lungs.
In an article published last week in Cell Host & Microbe, Yousef Abu Kwaik, Ph.D., professor, and Chris Price, Ph.D., senior research scientist, both of the Department of Microbiology and Immunology, and other researchers at the University of Louisville explain that L. pneumophila uses the same mechanism or virulence determinant in both amoeba and the accidental human host, but with different results. A virulence determinant is a gene or protein that plays a key role in disease development.
Legionnaire’s disease is a type of pneumonia caused by the bacterium L. pneumonphila. Legionnaire’s disease, named for one of the first documented outbreaks of the infection at an American Legion convention in Philadelphia in 1976, accounts for approximately 15 percent of pneumonia cases worldwide and has a mortality rate of 20 to 50 percent. L. pneumophila evolved as an environmental bacteria that lives in water, surviving and proliferating in several species of amoeba as its natural hosts. It is the only bacterial pathogen for which amoeba are the natural hosts and humans are accidental hosts.
The bacteria are transmitted to humans who accidentally inhale them in water particles that have been aerosolized by man-made devices such as cooling towers, whirlpools, fountains or misters such as those used in grocery stores or in water parks. These devices distribute the water particles into the air along with bacteria that may be present in the water.
When L. pneumophila enters its natural amoeba host, it injects a protein into the single-celled organism that prevents the amoeba from destroying the bacteria and provides a safe home in which the bacteria may grow and spread. When L. pneumophila enters human lungs, it injects the same protein into alveolar macrophages. Contrary to the outcomes in the amoeba, the bacterial protein stimulates an inflammatory response in human macrophages that contributes to pneumonia. This effect is counterproductive to the bacteria as it stimulates the human host to restrict the invading bacteria. The effect of the injected protein in human cells also contradicts evolutionary co-existence of the pathogen with the human host, which is considered an accidental host. The injected bacterial protein has evolved in Legionella to interfere with a specific process in the amoeba host that does not exist in the more evolved human cells, where a paradoxical effect is mounted in response.
“Our findings show for the first time that a bacterial ‘tool’ has evolved exclusively to manipulate an amoeba host-specific process, but it has a paradoxical effect on the human host,” Abu Kwaik said.
This knowledge may lead to methods that help reduce the bacteria’s ability to survive in amoeba in water sources, limiting the transmission of Legionnaire’s disease.
“Since the bacteria are not transmitted from one person to another, we have the opportunity to prevent transmission by targeting the bacterial protein with small molecule inhibitors,” Abu Kwaik said. “That would enable the amoeba to restrict and degrade the bacteria, blocking their amplification in the water system and, in turn, abolishing accidental droplet transmission to humans.”