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.
The antibiotics, odilorhabdins (ODLs), 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.
“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.”
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 bactericidal mechanism of ODLs and the fact that they bind to a site on the ribosome not exploited by any known antibiotic are very strong indicators that ODLs have the potential to treat infections that are unresponsive to other antibiotics,” said Mankin, who is also professor of medicinal chemistry and pharmacognosy.
Nosopharm researchers found that the ODL compounds successfully treated mice infected with several pathogenic bacteria and demonstrated activity against both Gram-negative and Gram-positive pathogens including carbapenem-resistant Enterobacteriacae. This was an important finding because Carbapenem-resistant Enterobacteriacae, or CRE, are a family of germs that have high levels of resistance to antibiotics — one study suggests that CRE, which are the common culprits in bloodstream and surgical site infections, contribute to death in up to 50 percent of patients who become infected.
New classes of antibiotics are much needed to combat that growing problem of antibiotic resistance that is rendering many current drugs ineffective. While ODLs have yet to be thoroughly investigated for their therapeutic potential, the researchers say that the study findings justify future research in this direction. “Collaborations with academia with renown expertise in antibiotics like the UIC team help us for this preclinical development,” said Philippe Villain-Guillot, co-founder and chief executive officer of Nosopharm.
