A new class of antibiotics found to combat drug resistance
WASHINGTON, April 6 (Xinhua) -- American and French researchers reported a new class of antibiotics from unconventional source and with distinct way of killing bacteria, suggesting the compound may be effective at treating drug-resistant or hard-to-treat bacterial infections.
The study, published in the latest version of Molecular Cell, described the new antibiotic called odilorhabdins, or ODLs, and, for the first time, how it works.
The new antibiotics are produced by symbiotic bacteria found in soil-dwelling nematode worms that colonize insects for food.
Researchers from the University of Illinois at Chicago (UIC) and Nosopharm, a biotechnology company based in Lyon, France, found the bacteria helped to kill the insect and secrete the antibiotic to keep competing bacteria away.
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 Yury Polikanov, assistant professor of biological sciences at UIC and the paper's corresponding author, "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, according to researchers.
"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 Alexander 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 said antibiotics that actually kill bacteria 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.
In France, the Nosopharm researchers tested the 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.
Carbapenem-resistant Enterobacteriacae, or CRE, are a family of germs that have high levels of resistance to antibiotics. One study suggested that CRE, which are the common culprits in bloodstream and surgical site infections, contributed to death in up to 50 percent of patients who become infected.