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New Treatment Eradicates MRSA Infection

‘Persister’ cells are the villains (November 13)

In the Nov. 13 issue of Nature, scientists at Northeastern University present a new approach to the treatment and elimination of methicillin-resistant Staphylococcus aureus (MRSA), a potent bacterium whose resistance to antibiotics has kept it one step ahead of researchers.

The so-called “superbug” infects 1 million Americans each year. A major problem with MRSA is the development of deep-seated chronic infections, such as osteomyelitis and endocarditis. Once established, these infections are often incurable, even when appropriate antibiotics are used.

The new work represents the culmination of more than a decade of research on a specialized class of cells produced by all pathogens called persisters. According to lead investigator Professor Kim Lewis, these cells evolved to survive. “Survival is their only function,” he said. “They don’t do anything else.”

Lewis and his colleagues posited that if they could kill these expert survivors, perhaps they could cure chronic infections — even those resistant to multiple antibiotics, such as MRSA. Further, said Brian Conlon, a post-doctoral researcher in Lewis’ laboratory and first author on the paper, “if you can eradicate the persisters, there’s less of a chance that resistance will develop at all.”

Lewis has found that persister cells achieve their singular goal by entering a dormant state that makes them impervious to traditional antibiotics. Since antibiotics 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 the infection to re-establish itself.

In the new study, Lewis’ team found that a drug called ADEP effectively wakes up the dormant cells and then initiates a self-destruct mechanism. The new approach completely eradicated MRSA cells in laboratory experiments and, importantly, in a mouse model of chronic MRSA infection.

Coupling ADEP with a traditional antibiotic, Conlon noted, allowed the team to completely destroy the bacterial population without leaving any survivors.

Source: Northeastern University; November 13, 2013.

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