The Arctic Sea has emerged as a potential treasure trove of fresh medicines.

Scientists have discovered fresh compounds in Arctic marine bacteria that could fight antibiotic-resistant infections and pave the way for a fresh generation of treatments.

Test: Bioprospecting for EPEC virulence inhibitors from metabolites of marine actinomycetes from the Arctic Ocean. Photo source: Risto Raunio / Shutterstock

Antibiotics are the backbone of newfangled medicine: without them, anyone with open wounds or requiring surgery would be constantly exposed to risky infections. Yet we still face a global antibiotic crisis as more and more resistant strains of bacteria evolve. But the pace of discovering fundamentally fresh antibiotics is much slower.

Novel hope from unexplored environments

But there is reason to hope: 70% of all currently licensed antibiotics come from actinomycetes in soil, and most environments on Earth have yet to be tested for their presence. So focusing the search on actinomycetes in other habitats is a promising strategy—particularly in unexplored environments like the Arctic Ocean—especially if it yields fresh molecules that neither kill the bacteria outright nor stop them from growing, but merely reduce their “virulence,” or ability to cause disease. That’s because it’s challenging for targeted pathogenic strains to develop resistance in such conditions, while such antiviral compounds are also less likely to cause unwanted side effects.

Advanced screening reveals fresh compounds

“In our study, we used high-content screening assays (FAS-HCS) and Tir translocation assays to specifically identify antiviral and antibacterial compounds from actinomycetes extracts,” said Dr. Päivi Tammela, professor at the University of Helsinki in Finland and corresponding author of the fresh study in Frontiers of Microbiology“We found two distinct compounds: a huge phospholipid that inhibits the virulence of enteropathogenic E. coli (EPEC) without affecting its growth, and a growth-inhibiting compound, both in actinobacteria from the Arctic Ocean.”

High-throughput automated screening of these candidate compounds was performed using a sophisticated workflow designed to handle the elaborate nature of microbial extracts. Tammela and colleagues developed a fresh set of methods that simultaneously test the antiviral and antibacterial activity of hundreds of unknown compounds. They focused on a strain of EPEC that causes severe—and sometimes fatal—diarrhea in children under five, particularly in developing countries. EPEC causes disease by attaching itself to cells in the human gut. Once attached to these cells, EPEC injects so-called “virulence factors” into the host cell to hijack its molecular machinery, ultimately killing it.

Discovery of antiviral and antibacterial compounds

The tested compounds came from four species of actinomycetes, isolated from invertebrates collected in the Arctic Sea off the coast of Svalbard during an expedition of the Norwegian research vessel Kronprins Haakon in August 2020. These bacteria were then cultured, their cells were extracted, and their contents were separated into fractions. Each fraction was then tested in vitro for EPEC adhesion to cultured colon cancer cells.

Scientists have discovered two previously unknown compounds with distinct biological properties: one from an unknown strain (T091-5) of the Rhodococcus genus and the other from an unknown strain (T160-2) of Kocuria. The compound from T091-5, identified as a huge phospholipid, showed potent antiviral activity by inhibiting the formation of actin pedestals and the binding of EPEC to the Tir receptor on the host cell surface. The compound from T160-2 showed potent antibacterial activity by inhibiting the growth of EPEC bacteria.

Promising results and next steps

Detailed analysis showed that the phospholipid from T091-5 did not inhibit bacterial growth, making it a promising candidate for antiviral therapy because it reduces the likelihood of resistance developing. In contrast, the compound from T160-2 inhibits growth and is being further investigated for its potential as a fresh antibiotic.

The researchers used HPLC-HR-MS2 to isolate and identify these compounds, with the phospholipid having a molecular weight of around 700 and its specific role being to disrupt the interactions between EPEC and host cells. “The next steps are to optimize the culture conditions to produce the compounds and isolate sufficient amounts of each compound to elucidate their respective structures and further investigate their respective bioactivities,” Tammela said.