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BACTERIA THAT TICK US OFF
Lyme disease, transmitted by the tick Ixodes scapularis, is the most common vector-borne illness in North America and Europe; approximately 20,000 people are infected with B. burgdorferi every year in the United States alone. Lyme disease is a multiple-system disorder that includes arthritis, neurological abnormalities, carditis, and cutaneous lesions. It causes life-long infection in laboratory mice; human Lyme disease may last years if left untreated. B. burgdorferi is one of the most invasive bacterial pathogens, causing persistent infection despite the development of strong immune responses. One research project in Liang’s laboratory is to find out how the Lyme disease agent is able to escape being killed by specific antibodies. “Developing a specific antibody response is an effective way for the host to eliminate bacterial infection, but in a B. burgdorferi infection the bug has the ability to change its surface antigenic architecture,” says Liang. “Once the host generates killer antibodies to a bacterial surface antigen, the bug shuts off expression of the antigen target. After killer antibodies disappear, the bacterium may start to remake the antigen again. The bug just plays its host and wins.” Liang hypothesizes that B. burgdorferi is able to sense specific antibodies and to selectively reduce expression of antigenic targets. His team is working on the elements that are potentially involved in regulation of the outer surface protein C (OspC). Liang has found that B. burgdorferi abundantly expresses OspC on its surface in the absence of an anti-OspC antibody but shuts off the OspC gene once the host has developed an anti-OspC immune response. “This is a powerful strategy B. burgdorferi uses to avoid elimination by specific antibodies and to cause persistent infection,” says Liang. “Our goal is to find out how the bug can do this.” Another major project is to investigate how B. burgdorferi induces arthritis. His team has successfully identified an arthritis-avirulent B. burgdorferi variant that is unable to cause arthritis in a mouse model. This variant has lost many genes. Liang believes one or more of the missing genes are responsible for the induction of arthritis. His team is adding these missing genes one by one back to the bacterium. “By using this strategy, we hope that we will be able to identify genes that are responsible for the development of Lyme arthritis,” Liang says. from Fall 2006 Issue |
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