Scientists study how malaria hacks cells to try and expand treatment options
Many parasites use the nutrients and resources of their human or animal host’s cells to reproduce themselves. In this study researchers identified specific genes that play a role in malaria infections in liver cells, which could lead to new anti-malaria drug targets in future.
Malaria is a wide-spread and potentially life-threatening disease caused by the Plasmodium parasite, which is transmitted via mosquito bites. Upon entry into the body, Plasmodium heads straight for the liver to reproduce - this early stage is ideal for antimalarial treatment because there are no disease symptoms yet and the disease can’t be transmitted.
In this study, researchers wanted to find specific changes to genes and proteins in infected liver cells that can change how an infection develops.
Using the gene-editing technology CRISPR-Cas9, the researchers were able to deactivate or “knockout” specific genes to see what changes when those genes are inactive. They then infected both normal and “knocked out” liver cells with malaria parasites. In particular, they were interested in changes to the formation of microtubules (MT). These tube-like structures are involved in, among other things, the movement of nutrients and materials inside cells, and they usually form a network around the cell nucleus.
One of the key findings is that Plasmodium hijacks the microtubules in liver cells - instead of the microtubules clustering around the nucleus delivering nutrients and materials to where the cell needs it, the microtubules cluster around the parasite delivering nutrients and materials to help the parasite reproduce. Researchers saw that when they knocked out a protein called CENPJ, the parasite became very successful at gathering microtubules around itself, and the parasites grew larger and made more copies of themselves. The scientists also identified several other genes that affect how severe a plasmodium infection becomes.
Researchers previously showed that other parasites reorganize microtubules to redirect resources within the cell to themselves. In this study, researchers confirmed that Plasmodium parasites may also use this strategy to redirect nutrients and other resources for their own development. In the future, scientists hope to use their understanding of how genes and parasites interact inside cells to identify new treatments for malaria.
Although researchers identified some interesting changes in liver cell proteins during the early stages of malaria, much more work is needed to understand exactly how Plasmodium changes cell chemistry and function so that specific targets for drugs can be identified.
Hundreds of thousands of deaths still occur each year from malaria, with a large number of these in Africa. According to the World Health Organisation, over 90% of global malaria cases in 2019 occurred in Africa, making this an important issue that requires ongoing efforts toward control and intervention.
Number of words: 457
Prior to initiating symptomatic malaria, a single Plasmodium sporozoite infects a hepatocyte and develops into thousands of merozoites, in part by scavenging host resources. We show that host microtubules dynamically reorganize around the developing liver stage (LS) parasite. Using a genome-wide CRISPR-Cas9 screen, we identified host regulators of cytoskeleton organization, vesicle trafficking, ER/Golgi stress and lipid biogenesis that regulate Plasmodium LS development. These novel regulators of infection, including Centromere Protein J (CENPJ), led us to interrogate how microtubule organizing centers (MTOCs) are regulated during infection. Foci of γ-tubulin localized to the parasite periphery; depletion of CENPJ exacerbated this re-localization and increased infection. Further, we show that the Golgi acts as a non-centrosomal MTOC by organizing γ-tubulin and stimulating microtubule nucleation at the parasite periphery. Collectively, we show that the Plasmodium LS recruits the host Golgi to form MT mediated conduits along which host organelles are recruited to the PVM, to support liver stage development. Our findings suggest many host-targeted pharmacological inhibitors may inhibit LS infection.
This summary is a free resource intended to make African research and research that affects Africa, more accessible to non-expert global audiences. It was compiled by ScienceLink's team of professional African science communicators as part of the Masakhane MT: Decolonise Science project. ScienceLink has taken every precaution possible during the writing, editing, and fact-checking process to ensure that this summary is easy to read and understand, while accurately reporting on the facts presented in the original research paper. Note, however, that this summary has not been fact-checked or approved by the authors of the original research paper, so this summary should be used as a secondary resource. Therefore, before using, citing or republishing this summary, please verify the information presented with the original authors of the research paper, or email [email protected] for more information.