Study: Unique Combination of Antibiotics Kills Methicillin-Resistant Staphylococcus aureus

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.

Here is a previous article on MRSA and using a cholesterol medicine to remove a protective carotenoid pigment in the cellular wall and allowing--in this case--a mouse's immune defenses to destroy the bacillus. This was very preliminary, and I do not see too much research after 2009, so I do not know if it is an issue of funding, a research dead end, ongoing research trials...or not.

http://www.staphnews.com/mrsa/cholesterol-lowering-drug-may-render-staph-bacteria-harmless/

And:

http://www.sciencemag.org/content/319/5868/1391.abstract

Abstract:

"Staphylococcus aureus produces hospital- and community-acquired infections, with methicillin-resistant S. aureus posing a serious public health threat. The golden carotenoid pigment of S. aureus, staphyloxanthin, promotes resistance to reactive oxygen species and host neutrophil-based killing, and early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. We determined the crystal structures of S. aureus dehydrosqualene synthase (CrtM) at 1.58 angstrom resolution, finding structural similarity to human squalene synthase (SQS). We screened nine SQS inhibitors and determined the structures of three, bound to CrtM. One, previously tested for cholesterol-lowering activity in humans, blocked staphyloxanthin biosynthesis in vitro (median inhibitory concentration ∼100 nM), resulting in colorless bacteria with increased susceptibility to killing by human blood and to innate immune clearance in a mouse infection model. This finding represents proof of principle for a virulence factor–based therapy against S. aureus."

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