Researchers from the University of Illinois at Chicago and Nosopharm, a biotechnology company based in Lyon, France, are part of an international team reporting on the discovery of a new class of antibiotics.
The antibiotic, first identified by Nosopharm, 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 bacterial infections.
Called odilorhabdins, or ODLs, the antibiotics are produced by symbiotic bacteria found in soil-dwelling nematode worms that colonize insects for food. The bacteria help to kill the insect and, importantly, secrete the antibiotic to keep competing bacteria away. Until now, these nematode-associated bacteria and the antibiotics they make have been largely understudied.
To identify the antibiotic, the Nosopharm research team screened 80 cultured strains of the bacteria for antimicrobial activity. They then isolated the active compounds, studied their chemical structures and engineered more potent derivatives.
The study, published in Molecular Cell, describes the new antibiotic and, for the first time, how it works.
UIC’s Alexander Mankin and Yury Polikanov are corresponding authors on the study and led the research on the antibiotic’s mechanism of action. They found that ODLs act on the ribosome — the molecular machine of individual cells that makes the proteins it needs to function — of bacterial cells.
“Like many clinically useful antibiotics, ODLs work by targeting the ribosome,” said Polikanov, assistant professor of biological sciences in the UIC College of Liberal Arts and Sciences, “but ODLs are unique because they bind to a place on the ribosome that has never been used by other known antibiotics.”
The UIC researchers, including graduate student Tanja Florin and postdoctoral research associate Malgorzata Dobosz-Bartoszek, also found that 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, director of the Center for Biomolecular Sciences in the UIC College of Pharmacy. “This miscoding corrupts the cell with flawed proteins and causes the bacterial cell to die.”
While many antibiotics can slow bacterial growth, Mankin says antibiotics that actually kill bacteria, called bactericidal antibiotics, are rare.
Read more at the University of Illinois at Chicago