Newly Discovered Malaria Mechanism Gives Hope to Pregnant Women

Resistance to malaria drugs means that pregnant women are unable to overcome the anaemia caused by the malaria parasite – and their babies are born undersized. A study by researchers at Karolinska Institutet and Uppsala University however, exposes the effects of malaria in pregnant women and shows how the PTEF protein is central to the infection. The study opens the way for new malaria drugs.

intestinal tumours, molecular scissors, disease, genetic, immune cells, drug development, Diabetes, Antibiotic, hydrogen generation, chronic obstructive pulmonary disease, malaria, photosynthesis, kidney failure, Brain tumours, mental health, blood cancer, cancer, dementia, cancer treatment, antibiotic resistance, blood vessel leakage, quantum simulations, atrial fibrillation, batteries, goiter treatment, terahertz radiation, organic materials , Guild of European Research Intensive Universities, gene copies, social anxiety, blue light screens, ‘Our hope is that these findings will make it possible to discover a way to selectively inhibit the TGF-beta signals that stimulate tumour development without knocking out the signals that inhibit tumour development, and that this can eventually be used in the fight against cancer,’ says Eleftheria Vasilaki, postdoctoral researcher at Ludwig Institute for Cancer Research at Uppsala University and lead author of the study. TGF-beta regulates cell growth and specialisation, in particular during foetal development. In the context of tumour development, TGF-beta has a complicated role. Initially, it inhibits tumour formation because it inhibits cell division and stimulates cell death. At a late stage of tumour development, however, TGF-beta stimulates proliferation and metastasis of tumour cells and thereby accelerates tumour formation. TGF-beta’s signalling mechanisms and role in tumour development have been studied at the Ludwig Institute for Cancer Research at Uppsala University for the past 30 years. Recent discoveries at the Institute, now published in the current study in Science Signaling, explain part of the mechanism by which TGF-beta switches from suppressing to enhancing tumour development. Uppsala researchers, in collaboration with a Japanese research team, discovered that TGF-beta along with the oncoprotein Ras, which is often activated in tumours, affects members of the p53 family. The p53 protein plays a key role in regulating tumour development and is often altered – mutated – in tumours. TGF-beta and Ras suppress the effect of mutated p53, thereby enhancing the effect of another member of the p53 family, namely delta-Np63, which in turn stimulates tumour development and metastasis.

Some 50 million pregnant women contract malaria every year. The most common and most dangerous parasite, “Plasmodium falciparum”, affects both female carriers of the malaria parasite and their unborn babies. The parasite retards fetal growth by consuming vital nutrients and the babies are born undersized. The women are also affected by anaemia when the parasite infects the placenta.

When the parasite sends a “glue protein” to the infected red blood membrane, tens, even hundreds of thousands of parasites can accumulate in the placental vessel wall and cause inflammation. First-time mothers, who have not built up immunity to the glue molecule, develop serious, chronic infections unless given prophylactic treatment. Due to growing resistance to modern malaria drugs, the treatments are not always that efficacious.

The team behind the study which is now published in Nature Microbiology found a certain protein in the parasite, PTEF, that is vital to the synthesis of the glue molecule to which the parasites attach themselves. The researchers show how PTEF binds direct to the cell’s protein-manufacturing ribosome, where it speeds up the production of new glue molecules.

“However, we can now stop this happening, and will one day be able to develop drugs that prevent the accumulation of parasites in the placenta,” says Professor Mats Wahlgren at Karolinska Institutet’s Department of Microbiology, Tumor and Cell Biology who was involved in the study. “We think that it will be possible in the future to deliver small molecules rather than traditional antibiotics to prevent pregnant women and the babies they are carrying from contracting malaria.”

Professor Suparna Sanyal at Uppsala University examined how the PTEF protein affected the ribosomes in E. coli bacteria models and found that it could stimulate protein synthesis in bacteria too.

The study was financed by several bodies, including the Swedish Research Council, the Swedish Foundation for Strategic Research and the Torsten Söderberg Foundation.

Source : Uppsala University