Dangerous brain parasite 'orders in' for dinner

Toxoplasma gondii is a single-celled parasite capable of infecting any animal, including humans. Up to one-third of infections in people happen through contact with cat waste or contaminated food or water. Although the parasite only causes acute disease in immune compromised persons, the infection is permanent and has been associated with neurological diseases such as schizophrenia and rage disorder. The parasite can invade virtually all types of cells in the body. Once inside, it begins to divide exponentially, a process that requires a great deal of resources. The parasite extracts most of the nutrients it needs for replication from its host cell, including essential amino acids like arginine. Because arginine is quickly depleted from the host cell, researchers wanted to learn where the parasite gets more of the amino acid to fuel its expansion into the hundreds. Researcher used a variety of mutant host cells to discern that a protein called GCN2 becomes activated as parasites consume the host cell's arginine supply & mapped out the cascade of events following GCN2 activation, leading him to discover that host cells infected with Toxoplasma express more of an arginine transporter called CAT1 at their cell surface. CAT1 brings more arginine into the infected cell so Toxoplasma can continue to binge. These findings suggest infected host cells can sense their nutrients being depleted. Oblivious to the parasites growing inside them, the host cells unwittingly gear up to bring in more arginine to compensate for the loss. The identification of proteins like GCN2 that are important for parasite growth and replication may serve as promising new drug targets to treat intracellular pathogens. Intracellular pathogens have to replicate without raising alarms, but in order to grow they need to pilfer nutrients from the host.

Return to top

                                     Sugars that coat proteins are a possible drug target for pancreatitis

Pancreatitis is an inflammation of the pancreas that accounts for 275,000 hospitalizations in the United States annually. Patients who suffer from hereditary pancreatitis have a 40 to 50 percent lifetime risk of developing pancreatic cancer. Researcher studies the progression of pancreatitis to pancreatic cancer & focused on a potentially powerful biomarker, a chemical structure created by complex sugar molecules called CA19-9, since CA19-9 is elevated in patients with pancreatitis and pancreatic cancer. Now researcher provide the first evidence that CA19-9 actually causes the disease it was correlated with as a biomarker, and suggest that blocking this complex sugar structure could be used therapeutically to prevent the progression from pancreatitis to pancreatic cancer. This is one of those unique opportunities where prophylactic intervention of pancreatitis may lead to prevention of pancreatic cancer in at-risk patients said by lead researcher. CA19-9, a complex sugar structure that coats many proteins but had not previously been ascribed with any particular function. A single enzyme controls the final step in production of CA19-9 in humans, but this enzyme is missing in rodents. Researcher generated mice that produced CA19-9, and surprisingly noted that the mice developed severe pancreatitis & findings position CA19-9 as an attractive therapeutic target for pancreatitis. In mice, CA19-9 recruits the immune system to repair injuries from pancreatitis. Researcher found that during this recruitment process, CA19-9 can also induce a cascade of biochemical reactions propelled by the release of deleterious digestive enzymes from the pancreas. This cascade opens a transformational gateway for cancer to develop and Engle also demonstrated that CA19-9 can dramatically accelerate the growth of pancreatic tumors. By targeting CA19-9 with antibodies in animal models, researcher were able to reduce the severity of pancreatitis and even prevent it from occurring.

SOURCE: HealthDay News, June 2019

Return to top

                                 Sustainable method to produce lifesaving opiate antidotes at reduced cost

Overdose from opiates has skyrocketed. Researcher identified a new method of producing these compounds using a microorganism discovered in a waste stream associated with the processing of opium poppy. This green chemistry process has the potential to greatly reduce the cost of the antidote drugs as well as decrease chemicals currently used that result in large amounts of harmful waste. Enzyme morphinan N-demethylase for more sustainable opiate processing. Enzymes perform reactions at efficiencies that surpass synthetic chemistry, thereby reducing the cost and impact of drug production on the environment. Researcher work now to optimize production levels of the enzyme to a scale sufficient for industrial processes. Naturally occurring opiates, such as morphine and thebaine, are produced in poppy species. Thebaine is converted into painkillers and opiate addiction treatments, the latter requiring a chemical reaction called N-demethylation. Current opiate N-demethylation utilizes noxious reagents, resulting in harmful waste. Microorganisms provide a rich source of enzymes useful for metabolizing unique compounds in their environment. Researcher probed an opium processing waste stream sample to identify an organism capable of catalyzing opiate N-demethylation. To identify a biocatalyst, a sludge sample was subjected to minimal medium containing thebaine as the sole carbon source. This led to the discovery of Thebainfresser, a Methylobacterium that metabolizes opiates by removing the N-methyl group. N-demethylation was induced following growth in minimal medium, a characteristic that led to discovery of the underlying gene MND (morphinan N-demethylase). The enzyme MND was found to be robust and versatile, N-demethylating structurally diverse substrates at varying temperatures and pH levels. In addition, MND tolerated selected organic solvents and maintained activity when immobilized. These properties make it an attractive candidate for further development for pharmaceutical manufacture.

Return to top