Scientists discover new compounds in Arctic marine bacteria that could fight antibiotic-resistant infections and pave the way for next-generation treatments.
Study: Bioscreening of inhibitors of EPEC virulence from metabolites of marine actinobacteria from the Arctic Sea. Image credit: Risto Raunio / Shutterstock
Antibiotics are the key to modern medicine: without them, anyone with open wounds or requiring surgery would be at constant risk of dangerous infections. However, we continue to face a global antibiotic crisis as more and more resistant strains of bacteria evolve. In contrast, the rate of discovery of fundamentally new antibiotics has been much slower.
New hope from unexplored environments
But there is reason for hope: 70% of all currently approved antibiotics come from actinobacteria in soil, and most environments on Earth have yet to be tested for them. Thus, focusing research on actinobacteria in other habitats is a promising strategy—especially from unexplored environments such as the Arctic Sea—especially if this yields new molecules that neither kill the bacteria directly nor prevent them from growing, but only reduce their “infectiousness.” » them or ability to cause disease. This is because it is difficult for targeted pathogenic strains to develop resistance under these conditions, while such anti-infective compounds are also less likely to cause unwanted side effects.
Advanced screening analyzes reveal novel compounds
“In our study, we used high content screening assays (FAS-HCS) and Tir displacement assays to identify specific anti-infective and antibacterial compounds from actinobacteria extracts,” said Dr. Päivi Tammela, professor at the University of Helsinki, Finland. the corresponding author of a new study in Frontiers in Microbiology. “We discovered two distinct compounds: a large phospholipid that inhibits the virulence of enteropathogenic E. coli (EPEC) without affecting its growth, and a compound that inhibits growth, both in actinobacteria from the Arctic Ocean.”
Automated high-throughput screening of these candidate compounds was performed using an advanced workflow designed to handle the complex nature of microbial extracts. Tammela and his colleagues developed a new series of methods that simultaneously test the anti-infective and anti-bacterial activity of hundreds of unknown compounds. They targeted a strain of EPEC that causes severe—and sometimes fatal—diarrhea in children under five, especially in developing countries. EPEC causes disease by attaching to human intestinal cells. Once attached to these cells, EPEC injects so-called “infectious factors” into the host cell to overwhelm its molecular machinery, eventually killing it.
Discovery of Anti-Infectious and Anti-Bacterial Compounds
The tested compounds came from four species of actinobacteria, isolated from invertebrates sampled in the Arctic Sea off Svalbard during a mission by the Norwegian research vessel Kronprins Haakon in August 2020. These bacteria were then cultured, the their cells were extracted and their contents divided into fractions. Each fraction was then tested in vitro against EPEC adherent to cultured colon cancer cells.
The researchers found two previously unknown compounds with distinct biological activities: one from an unknown strain (T091-5) in the genus Rhodococcus and another from an unknown strain (T160-2) of Kocuria. The compound from T091-5, identified as a large phospholipid, showed potent anti-infective effects by inhibiting the formation of actin scaffolds and the binding of EPEC to the Tir receptor on the host cell surface. The compound from T160-2 exhibited strong antibacterial properties by inhibiting the growth of EPEC bacteria.
Promising results and next steps
Detailed analysis revealed that the phospholipid from T091-5 does not inhibit bacterial growth, making it a promising candidate for anti-infective therapy as it reduces the chance of developing resistance. In contrast, the compound from T160-2 was found to inhibit growth and is being further investigated for its potential as a novel antibiotic.
The researchers used HPLC-HR-MS2 to isolate and identify these compounds, with the molecular weight of the phospholipid around 700 and its specific role in disrupting the interaction between EPEC and host cells. “The next steps are to optimize the culture conditions for compound production and to isolate sufficient amounts of each compound to elucidate their respective structures and further investigate their respective bioactivities,” said Tammela.
