Yeasts are everywhere, including inside and around our bodies, just like bacteria. You can also contract a yeast infection and get sick, just like you can with bacteria. About 150 million people are infected by yeast each year, and about 1.7 million people die from it, mostly immunocompromised people.
Unexpectedly, unexpectedly comparable chemical processes are used by yeast cells and human immune system cells to determine when to divide. Researchers at the University of Arizona have found small differences between the two types of cells. These differences could lead to the development of antifungal drugs that can kill disease-causing yeasts in the body while keeping the immune system safe.
Their research, which was published in the journal eLife, not only has ramifications for medication development, but it also sheds light on how an ancient growth regulation circuit that is present in all multicellular creatures evolved over time.
The proliferation of cells in all organisms, from humans to yeasts, is regulated by a collection of proteins collectively known as TORC1—short for Target of Rapamycin Kinase Complex 1. However, the protein that starts this process in yeasts, Ait1, has now been found and given the name Ait1. It is a nutrition sensor and a TORC1 regulator. When working properly, Ait1 turns off TORC1 in yeast cells to stop cell growth when the cells don’t have enough food.
According to study co-author Andrew Capaldi, an associate professor in the UArizona Department of Molecular and Cellular Biology and a member of the BIO5 Institute, “Ait1 is kind of like a hand holding TORC1 in place, with a finger that reaches over the top and flicks TORC1 on and off depending on how many nutrients a cell has.”
According to research conducted in the Capaldi Lab, in order to decide how quickly to grow, cells must first detect stress and famine. To find cures for a wide range of diseases, it is important to understand how TORC1 is turned on in different organisms.
Although TORC1 was initially found in yeast, it is also essential for the activation of immune system cells in humans. When TORC1 isn’t functioning properly, it can lead to the onset of diabetes, cancer, and a number of neurological conditions, including epilepsy and depression.
“Epilepsy or cancer can develop if TORC1 is overactive. “Added Capaldi. Depression may result if it is underactivedded Capaldi. Depression may result if it is underactive.” We refer to this as the “Goldilocks regulation.”
But there is a problem because yeast and humans use the same TORC1 pathway.
Capaldi says, “We are in big trouble if scientists make medicines that stop disease-causing yeasts from growing by blocking TORC1 because TORC1 also controls the growth of human immune cells and other things.”
For instance, rapamycin, a medication that binds to and inhibits TORC1, may readily stop the growth of yeast, thus effectively combating any infection, according to Capaldi. However, “it would be a disaster because that very same medicine is frequently used in transplant patients to suppress their immune systems.”
Although the TORC1 pathway in humans and yeast is highly similar, the researchers discovered that humans do not rely on Ait1 to regulate TORC1. So, medicines that specifically target Ait1 should stop yeast from multiplying instead of human immune cells.
In terms of evolution, Ait1 has only undergone significant change in the last 200 million years. A TORC1 regulator called Rheb seems to have left the cells of many animals around 200 million years ago, at the same time that Ait1 started to develop.
We demonstrated that some of the early TORC1 regulators discovered in humans, such as Rheb, had been lost in yeasts that had acquired Ait1 200 million years earlier, according to Capaldi. In the course of the evolution of other single-celled species, such as numerous parasites and plants, these same old regulators have also been lost. It is therefore quite plausible that additional single-celled organisms acquire novel regulators of their own that are comparable to Ait1. Now that they will also be good drug targets, folks can go out and seek them. ”
Ryan Wallace, who got his PhD in biochemistry and molecular biology from the University of Arizona in 2021 and works as a scientist for Aviva Systems Biology Corporation in San Diego, and Eric Lu, who got his bachelor’s degrees in molecular and cellular biology and biochemistry from the University of Arizona in 2021 and is now getting his PhD and medical degree at Wasatch University, wrote the study with Capaldi.
Tech Launch Arizona is an organization at the University of Arizona that helps bring university ideas to market. The researchers have applied for a patent on their discovery as a possible target for antifungal drugs.
