Brazilian researchers have discovered a key gene that regulates the virulence of the fungus that causes severe lung infections!

This species and other Aspergillus fungi are responsible for complications such as invasive pulmonary aspergillosis (IPA), a potentially fatal infection that can only occur in patients with a weakened immune system, such as those who are hospitalized in intensive care units (ICU). Depending on the patient's condition, IPA mortality ranges from 20% to 72%.

"We found that the suppression of a certain gene weakens virulence. When it was removed, the fungus remained viable, but important biological processes were affected, which made the fungus less virulent and increased the likelihood of its elimination with the help of existing drugs or even the human immune system," said Natalia Sayuri Vassano, the first author of the article.

Resistance to existing antifungal drugs is common, and patients with chronic VBP may undergo a course of treatment for years. Available treatments can also have side effects such as vomiting and headaches.

"In recent years, very few new antifungal drugs have been approved for use. However, molecules that can have a complementary effect in relation to others already used have shown significant potential and are highly likely to be approved," said Andre Damasio, co-author, co-author of the article and professor of IB-UNICAMP.

Another correspondent is Nilmar Moretti, professor at the Federal University of São Paulo School of Medicine (EPM-UNIFESP). He and Damasio work at the National Institute of Science and Technology (NIST) to study human pathogenic fungi.

Another research group has recently patented a new compound that fights drug-resistant fungi in combination with commercially available antifungal agents. Two of the researchers who participated in this study are co-authors of this article.

The strain without the sirtuin E gene grew less in the laboratory. The infected mice were still alive 15 days after vaccination with the fungus. Photo: Natalia Sayuri Vassano

A group of Brazilian researchers has found a potential target for new therapeutic strategies to combat fungal infections, in particular infections caused by Aspergillus fumigatus. The article reporting on the discovery was published in the Communications Biology journal.

The next steps of the research team include the search for a molecule that inactivates sirtuin E, the protein that showed the best results among the six tested. If they find it, it can serve as a basis for a medicine that will make the mushroom more sensitive to existing drugs.

Sirtuins, a class of proteins analyzed in the study, are also present in the human body and play a role in a number of cellular and physiological processes. Researchers found that 25% of the studied sirtuins were identical in fungi and humans; a low percentage means that sirtuin can be a safe target for drugs.

"For the future medicine for this purpose, it will not necessarily be bad to inhibit human sirtuin, as well as mushroom sirtuin, but we should pay attention to this. Minor side effects may be acceptable for new drugs, provided that the benefits are significant," Damasio said.

One of the difficulties in finding new antifungal agents is precisely the similarity of some proteins found in fungi and humans. The reason is that from an evolutionary point of view we are closer to mushrooms than, for example, to bacteria. The genes of some common ancestor have been preserved in both humans and fungi. This partly explains why it was possible to produce so many drugs to fight bacteria.

To get the results, the researchers derived seven mutant strains of A. fumigatus, in one of which six sirtuins were removed, and in each of the others another sirtuin was inactivated using the CRISPR-Cas9 gene editing technique.