A group led by researchers from the University of São Paulo (USP), in São Carlos, identified a series of bioactive compounds in a collected marine sponge in the Fernando de Noronha archipelago, in Pernambuco. Some substances have been shown to be able to kill bacteria resistant to currently available antibiotics, which paves the way for the development of new drugs. The study, supported by FAPESP, was published in the Journal of Natural Products.
“This marine sponge had already been studied before by groups from abroad, mainly in the 1990s. We then used modern techniques to evaluate the substances of its secondary metabolism, search for new molecules and test its biological activity. The greatest potential was found against bacteria resistant to current antibiotics”, says Vítor Freire, who carried out the study as part of his doctorate at the São Carlos Institute of Chemistry (IQSC-USP).
THE antibiotic resistance is considered one of the biggest global public health problems by the World Health Organization (WHO). According to a report commissioned by the British government, published in 2016, deaths caused by infections caused by resistant bacteria are expected to reach 10 million people a year by 2050. Hence the importance of finding new effective antibiotics.
The marine sponge of the species Agelas dispar occurs in the Caribbean and in part of the Brazilian coast. Because they are some of the longest living organisms on Earth and live fixed on the marine substrate, over millions of years sea sponges have developed a complex metabolism, producing substances essential for competition with other invertebrates and to avoid infections by pathogenic bacteria. . In the study published now, the substances with the greatest therapeutic potential were three different types of ageliferins, named after the sea sponge genus Agelas.
“Another important factor is the ability of sponges to store substances from symbiotic microorganisms, which also help them to defend themselves. Therefore, when we analyze the compounds found in these animals, it is not always possible to know what was produced by them and what is product of its microbiota”, explains Roberto Berlinck, professor at IQSC-USP and coordinator of the study. The work integrates two projects coordinated by Berlinck and financed by FAPESP. One of them is part of the Biota / FAPESP Program.
Tumors and bacteria
Thirteen compounds were tested in an ovarian tumor cell line known as OVCAR3, but showed no biological activity. Other groups had already tested ageliferins in lung, colon and breast tumors. In previous studies, antitumor action was also not observed.
Three substances, however, were effective in eliminating antibiotic-resistant bacteria. This part of the study was carried out at the Adolpho Lutz Institute (IAL), under the coordination of researcher André Gustavo Tempone, also supported by FAPESP. Six species were subjected to these compounds, two of them Escherichia coli and Enterococcus faecalis, some of the most common and found in different environments, including the human body.
The other four bacteria are listed by the WHO as priorities for the development of new antibiotics: Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. These are some of those responsible for most hospital infections, as they are able to escape the action of antibiotics available on the market.
The researchers wanted to know, however, whether the use of ageliferins could lead to hemolysis of red blood cells in the intestine, a common adverse effect in patients undergoing chemotherapy who need antibiotics and that can lead to death. In mouse cells, the compounds did not cause harm. This result indicates a good potential for the development of new drugs.
The group’s objective now is to analyze other marine sponges with the same methodology used to discover the new compounds. “Investigating how these substances are produced is extremely important, since they are distributed among some classes of sponges and may in the future help treat diseases”, concludes Freire, who is currently doing a postdoctoral work at the National Cancer Institute, in the United States.