Parasitic proteins crucial for cell traversal activity identified

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Researchers from the Walter and Eliza Hall Institute of Medical Research (Melbourne, Australia) have identified two proteins that allow malaria parasites to traverse host cell walls and establish infection in the human liver. These could be targeted in the future development of vaccines or antimalarial drugs.

The study, published recently in Cell Reports, highlighted two proteins, sporozoite microneme protein essential for cell traversal (SPECT) and perforin-like protein 1, PLP1, as important for transcellular migration. On entering the human host, malaria parasites must first travel from the site of the mosquito bite to the liver – a critical first step in infection. The molecular basis of sporozoite migration to the liver has previously been poorly understood, in addition, evidence demonstrating the importance of this path in vivo is lacking.

The team generated malaria parasites deficient in SPECT and PLP1 and tested these pathogens in humanized mouse models. They discovered that the loss of SPECT and PLP1 proteins did not affect the parasite’s growth in erythrocytes; in addition, the spopzoites could infect hepatocytes in vitro. However, the researchers observed that parasites lacking SPECT and PLP1 were unable to establish normal liver infection in the mice, demonstrating these proteins are critical for transcellular migration.

Author, Justin Boddey (Walter and Eliza Hall Institute) explained: “We have shown that Plasmodium falciparum employs a technique called cell traversal to quickly move through host cells in their path as they seek out liver cells to infect.”

“Our study identified that P. falciparum parasites traverse human cells – effectively walking through cell walls – using two proteins called SPECT and PLP1 to achieve this superpower. This allows parasites to get from the skin to the liver very quickly following a mosquito bite.”

The team hope these proteins could be targeted in the development of future antimalarial drugs or vaccines. Boddey concluded: “Our long-term goal is to eradicate malaria, so we have to look at ways of breaking the cycle of infection. A vaccine or treatment that halts the liver-stage infection offers the best chance of eradication because it stops parasites before they take hold.”

Sources: Yang ASP, O’Neill MT, Jennison C et al. Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice. Cell Rep. doi:10.1016/j.celrep.2017.03.017 (2017) (Epub ahead of print); www.wehi.edu.au/news/malaria-parasites-walk-through-walls-infect-humans

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