A research team from Finland and Norway has identified two candidate anti-toxic compounds against enteric pathogens. E. coli Marine actinomycete strains from the bacterial metabolite (EPEC) infection Cochlea and Rhodococcus From the Arctic Ocean.
“We show that advanced screening assays can identify anti-toxic and antibacterial metabolites from actinomycete extracts,” says Professor Paivi Tamela from the University of Helsinki.
“We discovered compounds in the Arctic actinomycete that inhibit virulence without affecting EPEC growth, as well as compounds that inhibit growth.”
Professor Tamera and his colleagues have developed a series of new methods that allow them to simultaneously test the antitoxic and antibacterial effects of hundreds of unknown compounds.
They targeted a strain of EPEC that causes severe, sometimes fatal, diarrhea in children under the age of 5, especially in developing countries. EPEC attaches to cells in the human intestine and causes disease.
Once EPEC attaches to these cells, it injects so-called “virulence factors” into the host cell that hijack its molecular machinery and ultimately kills the cell.
The compounds tested were extracted from four species of actinomycetes isolated from invertebrates collected in the Arctic waters off the coast of Svalbard during an expedition by a Norwegian research vessel. Cronprince Haakon August 2020.
These bacteria were cultured, the cells were extracted, and their contents were separated into fractions.
Each fraction was then tested in vitro against EPEC attached to cultured colon cancer cells.
The researchers discovered two previously unknown compounds with strong anti-toxic or anti-bacterial activity: one from an unknown strain of the genus (called T091-5); Rhodococcusand another strain from an unknown strain of this genus (T160-2). Cochlea.
These compounds exhibited two complementary biological activities.
First, it inhibits the formation of the so-called “actin pedestal” by EPEC bacteria, a key step in the attachment of this pathogen to the host intestinal wall.
The second is to block EPEC binding to so-called Tir receptors on the surface of host cells, a necessary step to rewire intracellular processes and cause disease.
Unlike compounds in T160-2, compounds in T091-5 did not slow the growth of EPEC bacteria.
This means that T091-5 is the most promising of the two strains, as EPEC is unlikely to eventually develop resistance to its antivirulence effects.
Using advanced analytical techniques, the authors determined that the active compounds in T091-5 were likely phospholipids, a type of fatty phosphorus-containing molecule that plays an important role in cellular metabolism.
“The next steps are to optimise the culture conditions for compound production and to isolate sufficient quantities of each compound to elucidate their structures and further explore their respective biological activities,” Prof Tamera said.
of Survey results Published in today's journal The cutting edge of microbiology.
_____
Tuomas Pirko others2024. Bioprospecting EPEC virulence inhibitors from metabolites of an Arctic marine actinomycete. Front. Microbiol 15;doi: 10.3389/fmicb.2024.1432475
Source: www.sci.news