Proteins Help Lyme Hide from Immune System

Borrelia burgdorferi, Courtesy Dave Dorward, PhD, NIH

Proceedings of the National Academy of Sciences of the United States of America (PNAS), (Pereira, M.J. et al.) published “Lipoproteome screening of the Lyme disease agent identifies inhibitors of antibody-mediated complement killing” on March 21, 2022. In this study, researchers identified two lipoproteins (ElpB and ElpQ) that formed a tight bond to human C1 (a protein complex that activates a pathway of the complement system). These proteins assist Borrelia burgdorferi (Lyme bacteria) to hide from the human complement system, which is the first defense in the immune system. This evasion of the immune system allows for dissemination of bacteria throughout the human body (blood, tissues, organs, bone, etc.) resulting in Lyme disease.

These findings set the stage for identifying how to create a stronger barrier to evasion of the human immune system, or to potentially weaken the Lyme bacteria to prevent dissemination and proliferation throughout the human body. To demonstrate that these proteins protected B. burgdorferi from complement killing, the researchers developed an assay to test (in vitro) these two proteins in their ability to protect the Lyme bacteria from the human complement system. They found that Lyme bacteria expressing ElpQ had a significantly higher survival rate (321-fold) than controls, and though bacteria expressing ElpB also had a higher survival rate, the increase was not statistically significant.

Researchers state that further investigation is needed to determine whether these two proteins (ElpB and ElpQ) can protect B. burgdorferi from the complement system in a live animal host. In order to test this theory, they will need to genetically modify B. burgdorferi to create strains lacking both ElpB and ElpQ proteins. These findings provide potential for identifying new Lyme therapeutics or targets for vaccine development. 

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