Researchers of the University of Illinois at Chicago and Nosopharm, a biotechnology company in France, are part of a team reporting on the discovery of a new class of antibiotics. First identified by Nosopharm, it is unique and promising on two fronts: its unconventional source and its distinct way of killing bacteria, both of which suggest the compound may be effective at treating drug-resistant or hard-to-treat infections.
Called odilorhabdins, or ODLs, the antibiotics are produced by symbiotic bacteria found in soil-dwelling nematode worms that colonise insects for food. The bacteria help to kill the insect, and secrete the antibiotic to keep competing bacteria away.
The Nosopharm team screened 80 cultured strains of the bacteria for antimicrobial activity. They isolated the active compounds, studied their chemical structures and engineered more potent derivatives. The study has been published in the journal, Molecular Cell.
UIC’s Alexander Mankin and Yury Polikanov found ODLs act on the ribosome — the molecular machine that makes proteins cells needed to function — of bacterial cells. “Like many clinically useful antibiotics, ODLs work by targeting the ribosome,” said Polikanov, “but ODLs are unique because they bind to a place on the ribosome that has never been used by other known antibiotics.”
When bound to the ribosome, the antibiotic disrupts its ability to interpret and translate genetic code. “When ODLs are introduced to the bacterial cells, they impact the reading ability of the ribosome and cause the ribosome to make mistakes when it creates new proteins,” said Mankin. “This miscoding corrupts the cell with flawed proteins and causes the bacterial cell to die.”
While many antibiotics can slow bacterial growth, antibiotics that actually kill bacteria, called bactericidal antibiotics, are rare. In France, Nosopharm researchers tested ODL compounds against bacterial pathogens, including many known to develop resistance. “We found that the ODL compounds cured mice infected with several pathogenic bacteria and demonstrated activity against both Gram-negative and Gram-positive pathogens, notably including carbapenem-resistant Enterobacteriacae,” said co-corresponding author Maxime Gualtieri,
co-founder and chief scientific officer of Nosopharm.
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