A new class of antibiotics to fight drug resistance
“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.
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 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.
“In this case, the combined expertise of the industry, which has the resources to develop new compounds, and the academia, which has the research and lab capabilities to understand how the compounds work, have enabled the development of this new class of antibiotics,” Mankin said.
“The collaboration between multiple labs with diverse areas of expertise add credibility to the research,” Polikanov said.
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.
