According to new research published this week in the journal Nature, an acyldepsipeptide antibiotic called ADEP in combination with the bactericidal antibiotic drug rifampicin eliminates the methicillin resistant Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that is resistant to many antibiotics. It is responsible for several chronic infections such as osteomyelitis, endocarditis, or infections of implanted medical devices. These infections are often incurable, even when appropriate antibiotics are used.
Senior author of the study, Prof Kim Lewis of Northeastern University, suspected that a different adaptive function of bacteria might be the true culprit in making these infections so devastating.
The study represents the culmination of more than a decade of research on a specialized class of cells produced by all pathogens called persisters.
“These cells evolved to survive. Survival is their only function. They don’t do anything else,” Prof Lewis said.
Prof Lewis and his colleagues posited that if they could kill these expert survivors, perhaps they could cure chronic infections.
They have found that persisters achieve their singular goal by entering a dormant state that makes them impervious to traditional antibiotics. Since these drugs work by targeting active cellular functions, they are useless against dormant persisters, which aren’t active at all. For this reason, persisters are critical to the success of chronic infections and biofilms, because as soon as a treatment runs its course, their reawakening allows for the infection to establish itself anew.
A recent study found that a drug called ADEP effectively wakes up the dormant cells and then initiates a self-destruct mechanism.
Coupling ADEP with rifampicin, allowed the team to completely destroy the bacterial population without leaving any survivors.
The new approach completely eradicated MRSA cells in a variety of laboratory experiments and, importantly, in a mouse model of chronic MRSA infection.
While ADEP targets MRSA, the team believes similar compounds will be useful for treating other infections as well as any other disease model that can only be overcome by eliminating a population of rogue cells, including cancerous tumors. They are pursuing several already.
Bibliographic information: Conlon BP et al. Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature, published online November 13, 2013; doi: 10.1038/nature12790