In a recent study, Yale researchers pinpointed specific targets in the human body where pathogens carried by mosquitoes, ticks, and other vectors attach. They believe these findings could help combat the growing threat of vector-borne diseases, a major global cause of death.
The study, published in Cell, aimed to understand how pathogens interact with humans to cause infections and diseases. Thomas Hart, PhD, a postdoctoral associate at Yale School of Medicine, explained, “We tested interactions between thousands of human proteins and several microbial pathogens to identify crucial binding points.”
Thomas Hart, PhD, explained that pathogens must bind with host molecules, particularly host proteins, to infect the host, evade the immune system, and cause symptoms. In their study, PhD researchers used a yeast display library of 3,324 human proteins to examine interactions with 82 pathogen samples.
This research enhances our understanding of how infectious diseases develop and identifies new targets for vaccines and treatments. One surprising discovery was that Borrelia burgdorferi, the bacterium causing Lyme disease, interacts with epidermal growth factor (EGF), which could impact Lyme disease pathogenesis, noted corresponding author Erol Fikrig, MD.
The researchers discovered that protein disulfide isomerase helps Rickettsial pathogens invade cells, causing diseases like spotted fever and scrub typhus. Co-author Noah Palm, PhD, a Yale School of Medicine professor, highlighted that advanced technologies for unbiased screening of the entire proteome reveal how pathogens invade and manipulate human hosts, sense the host’s environment and immune system, and trigger specific disease processes. He also noted that these technologies uncover new methods through which mammals can recognize and defend against various pathogens.
Noah Palm, PhD, noted that many of the host-microbe interactions discovered were surprising and unpredictable. These findings reveal new ways pathogens interact with hosts, which could lead to the development of innovative anti-infective treatments targeting these interactions.
The researchers created a valuable resource for investigating how pathogens like Plasmodium, Leptospira, and Borrelia burgdorferi attach to different host targets. This provides insights into malaria, Leptospirosis, and Lyme disease.
Thomas Hart stressed the significance of these discoveries, stating, “This research expands our knowledge of how infectious diseases develop and identifies promising new targets for vaccines and therapies to prevent better and treat these illnesses.”
Journal reference:
- Thomas M. Hart, Nicole D. Sonnert et al., An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms. Cell. DOI: 10.1016/j.cell.2024.05.023.