"DRUG RESISTANT BACTERIA WILL BE KILLED BY NEW CLASS OF ANTIBIOTICS DISCOVERED

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Researchers from the University of Illinois at Chicago and Nosopharm, a biotechnology company based in Lyon, France, identified 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.

         "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 anwhen 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."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.

             According to the World Health Organization, antibiotic resistant is one of the biggest threats to global health today and a significant contributor to longer hospital stays, higher medical costs and increased mortality.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.

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.

               The researchers say this study is a testament to the growing trend of international and cross-disciplinary collaboration, which is needed to combat the growing and global threat of antibiotic resistance.