Fungus discovered in eastern Mexico shows antimicrobial activity

In 2021, chemist Itzel Rubí Yeverino hiked up to the El Caracol waterfall deep in the Sierra Madre Oriental, the mountain system that runs through eastern Mexico. In a small pond near the waterfall, she found a fungus growing on a submerged piece of wood. New findings reveal that molecules produced by this fungus showed antimicrobial activity against Acinetobacter baumannii, an antibiotic-resistant pathogen responsible for some hospital-acquired infections.

These findings, described in a paper recently published in ACS Omega (DOI: 10.1021/acsomega.4c10990), are part of the efforts of a research group led by Mario Figueroa, a biochemist and professor in the Department of Chemistry at the National Autonomous University of Mexico (UNAM). He and his colleagues are focusing on the bioprospecting of microorganisms found in Mexico's ecosystems for the development of new medicines or agrochemicals.

“Bioprospecting is the search for products from nature that can be used primarily for medical purposes,” says Figueroa. Bioprospecting researchers try to isolate substances—called secondary metabolites—that organisms such as fungi or plants produce to defend themselves or adapt to their environment. Figueroa’s research groups focus on previously unexplored ecosystems such as that of the Sierra Madre Oriental.

Searching for freshwater fungi in the Sierra Madre Oriental was Rubí Yeverino’s idea. In part, she wants to “start changing the idea that everything there [in northeastern Mexico] is flat and there is nothing but tumbleweeds and dirt,” she says.

After collecting her samples in March 2021 and cultivating them for a few months, she took them back to the UNAM chemistry faculty to isolate their metabolites. Realizing that these compounds were novel, the team began testing them against a group of critically threatening antibiotic-resistant pathogens that includes A. baumannii. According to World Health Organization criteria, A. baumannii infection has a high mortality rate in health-care settings, owing in part to an increasing trend of drug resistance in the microbe, and is likely to be untreatable in the future.

Figueroa’s team isolated five metabolites, which they identified as cyclodepsipeptides, from the fungi. Because of the scarcity of the samples, the researchers were able to test only two metabolites against the pathogens. They tested the metabolites against two strains of A. baumannii, which is a gram negative bacterium. Gram-negative bacteria are known to be harder to eradicate than gram-positive ones because of their ability to resist many antibiotics. The first strain of A. baumannii was susceptible to the antibiotic gentamicin for treatment. The second was a multidrug-resistant strain isolated from a patient being treated for burns at Mexico’s National Institute of Rehabilitation.

One of the metabolites inhibited growth of the first strain by 13.3% and the multidrug-resistant strain by 35.5%; the other metabolite was not effective against A. baumannii but inhibited growth by 42.9% in Staphylococcus aureus, another high-priority pathogen resistant to antibiotics.

Now that the researchers have discovered the metabolites’ antimicrobial activity against A. baumannii, the next step is to test them in preinfected organisms. If the larvae they use for these tests survive the infection, the researchers will be able to make further progress toward the possibility of developing a new drug.

Nicholas Oberlies, a biochemist at the University of North Carolina Greensboro who was not involved in the study, is optimistic about Rubí's findings, but he is cautious about saying they will result in a drug that works against A. baumannii. Figueroa's research group still has many challenges to overcome, such as identifying the mechanism by which the fungal compounds work against this pathogen. “If the mode of action is unique, that will help. If the mode of action is something that other people have already figured out, then that will potentially stop the whole process,” he says. Nevertheless, Oberlies applauds Figueroa’s determination to test compounds against gram-negative pathogens.