A group that involves scientists from Brazil and the United States has uncovered how structures present in fungi act in communication between individuals of the same species. The discovery, detailed in an article published in the journal mBio, makes it possible to develop more effective treatments against fungal infections.
“There was a hypothesis that cells of the same species of fungus could communicate through these structures, called extracellular vesicles. We showed, with different methodologies, that this occurs in three species”, says Fausto Almeida, professor at the University of São Paulo (USP) Ribeirão Preto School of Medicine and coordinator of the research.
Extracellular vesicles are nanostructures produced by all living cells and carry molecules such as proteins, genetic material and metabolites, among others, to the extracellular space, the one outside the cell. They act in the regulation of physiological processes, as well as in the response to specific environmental conditions, both in infectious and other processes.
“By making this communication and modulating some phenomena, extracellular vesicles become potential targets for therapies. If we can change or even interrupt this communication channel, we will reap interesting results in the future”, says Almeida.
In previous work, published in Nature Communications, the group had shown the role of vesicles in fungal infection. Cryptococcus neoformans.
Now, researchers have demonstrated how extracellular vesicles are used by disease-causing fungi. Candida albicans, aspergillus fumigatus and Paracoccidioides brasiliensis. These species are responsible for a large part of the fungal infections that occur in the world today, the latter being relevant especially for Brazil. All three are known for the severity of the infections they can cause.
This is one of the factors that cause 1.6 million people to die a year worldwide from this type of infection, a possibly underestimated number, according to a study published by the group in 2019.
The investigation was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp) and the collaboration of researchers from the Carlos Chagas Institute (ICC/Fiocruz), in Curitiba, and the Johns Hopkins Bloomberg School of Public Health, in the United States.
fungus riddle
“Extracellular vesicles and their contents are able to regulate gene expression not only in the individual itself, but also in neighboring cells. [da mesma espécie]. With this, they prepare the entire colony to respond and overcome the hostility imposed by the host to try to eliminate the infection”, explains Tamires Bitencourt, first author of the article, carried out during her postdoctoral internship at USP.
The researchers demonstrated that the communication promoted by the vesicles takes place in different cell signaling pathways, depending on the species. This is very promising for the search for broad-spectrum treatments.
The experiments carried out with the three types of fungi that cause infections consisted of provoking a stimulus that generated a response. The vesicles were then removed and transferred to a new culture of the same species that had not undergone any intervention. As a consequence, the “control” colony (not stimulated) presented the same responses as the one that had received the stimulus.
With Paracoccidioides brasiliensisapplied the drug tunicamycin, known to cause stress in the cell’s endoplasmic reticulum – an organelle that, among other functions, processes the proteins produced by the fungus.
The researchers observed that, when transferring the vesicles treated with tunicamycin to the cells that did not undergo the intervention, they had the cell signaling pathway known as UPR activated, in an attempt to restore the balance of the fungal organism.
in cultures of aspergillus fumigatusa microorganism known to cause the so-called invasive pulmonary aspergillosis, the researchers irradiated ultraviolet (UV) light, since the species is known to adapt to this type of stress, which causes DNA damage.
When absorbed by the fungi that did not receive the UV rays, the extracellular vesicles caused the cells to reduce colony growth. In addition, the akuA gene, known precisely for repairing DNA damage, was expressed quite intensely.
interventions in Candida albicans occurred with the alteration of the morphology of the cells through stimuli that made them change from the yeast to the filamentous format. This is a way for the fungus to lodge in different niches within the host and increase virulence.
As a response to the experiment, changes were observed that indicate the formation of hyphae, structures involved with tissue invasion and maintenance of virulence in fungi. When they form, they show that the fungus is responding to the stimulus.
The researchers now intend to make changes to proteins carried by the vesicles to try to kill the fungi or reduce their resistance to existing antifungals, among other possible interventions.
“It is as if we have discovered the secret code by which fungi communicate. Now we are going to use it to attack the enemy”, says Almeida.
Source: CNN Brasil
