A team of researchers from Finland and Norway has identified two potential antivirulence compounds for enteropathogenic Escherichia coli (EPEC) infections among bacterial metabolites harvested from strains of marine actinobacteria Kocuria and Rhodococcus from the Arctic Sea.
The T091-5 strain of the genus Rhodococcus. Image credit: Pylkkö et al., doi: 10.3389/fmicb.2024.1432475.
“We show how advanced screening assays can identify antivirulence and antibacterial metabolites from actinobacteria extracts,” said University of Helsinki’s Professor Päivi Tammela.
“We discovered a compound that inhibits EPEC virulence without affecting its growth, and a growth-inhibiting compound, both in actinobacteria from the Arctic Ocean.”
Professor Tammela and colleagues developed a new suite of methods that can test for the antivirulence and antibacterial effect of hundreds of unknown compounds simultaneously.
They targeted an EPEC strain that causes severe — and sometimes deadly — diarrhea in children under five, especially in developing countries. EPEC causes disease by adhering to cells in the human gut.
Once it adheres to these cells, EPEC injects so-called ‘virulence factors’ into the host cell to hijack its molecular machinery, ultimately killing it.
The tested compounds were derived from four species of actinobacteria, isolated from invertebrates sampled in the Arctic Sea off Svalbard during an expedition of the Norwegian research vessel Kronprins Haakon in August 2020.
These bacteria were then cultured, their cells extracted, and their contents separated into fractions.
Each fraction was then tested in vitro, against EPEC adhering to cultured colorectal cancer cells.
The researchers found two unknown compounds with strong antivirulence or antibacterial activity: one from an unknown strain (called T091-5) of the genus Rhodococcus, and another from an unknown strain (T160-2) of the genus Kocuria.
The compounds showed two complementary types of biological activity.
First, by inhibiting the formation of so-called ‘actin pedestals’ by EPEC bacteria, a key step by which this pathogen attaches to the host’s gut lining.
Second, by inhibiting the binding of EPEC to the so-called Tir receptor on the host cell’s surface, a step necessary to rewire its intracellular processes and cause disease.
Unlike the compounds from T160-2, the compound from T091-5 didn’t slow down the growth of EPEC bacteria.
This means that T091-5 is the most promising strain of the two, as EPEC is less likely to ultimately evolve resistance against its antivirulence effects.
With advanced analytical techniques, the authors determined that the active compound from T091-5 was most likely a phospholipid: a class of fatty phosphorus-containing molecules that play important roles in cell metabolism.
“The next steps are the optimization of the culture conditions for compound production and the isolation of sufficient amounts of each compound to elucidate their respective structures and further investigate their respective bioactivities,” Professor Tammela said.
The findings appear today in the journal Frontiers in Microbiology.
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Tuomas Pylkkö et al. 2024. Bioprospecting of inhibitors of EPEC virulence from metabolites of marine actinobacteria from the Arctic Sea. Front. Microbiol 15; doi: 10.3389/fmicb.2024.1432475
Source : Breaking Science News