AsianScientist (Sep. 15, 2017) -Scientists in Hong Kong have found a non-antibiotic drug that can be used to treat methicillin resistant Staphylococcus aureus (MRSA) infection. They published their work in the journal mBio.
The indiscriminate use of antibiotics has led to the rapid emergence of multidrug resistant (MDR) bacteria. Antibiotics are no longer as effective in controlling infections. Thus, researchers around the world have been searching for alternative strategies for treating bacterial infections without incubating the emergence of drug resistant bacteria.
MRSA is a strain of Staphylococcus aureus (S. aureus) that is resistant to antibiotics including methicillin and other commonly used antibiotics such as oxacillin, penicillin, amoxicillin and cephalosporins. MRSA usually causes skin and soft tissue infections such as pimples, boils, abscesses or wound infections. The infected area may be red, swollen and painful, or it may produce pus. Sometimes, more serious conditions such as bloodstream infections, lung infections or necrotizing fasciitis may occur.
In this study, a team of scientists led by Dr. Richard Kao Yi-tsun at Hong Kong University used chemical genetics to tackle MRSA infection. The team screened more than 50,000 structurally diverse small molecule compounds to identify compounds that can reduce the virulence of MRSA.
A compound named NP16 was found to strongly inhibit on the production of staphyloxanthin, a golden-colored pigment in S. aureus known for its ability to promote bacterial invasion and contribute to the resistance to reactive oxygen species (ROS) and host neutrophil-based killing.
Using mutational studies and enzymatic assays coupled with liquid chromatography–mass spectrometry, the research team was able to identify dehydrosqualene desaturase (CrtN) as the molecular target of NP16. The efficacy of NP16 in reducing MRSA virulence was further validated in in vitro cell-based tests and in in vivo animal studies. S. aureus treated with NP16 were more susceptible to attack by human neutrophils and to innate immune clearance in a mouse infection model.
These findings won the first prize Innovation Academy Award at the 4th International Conference on Prevention & Infection Control in Geneva, Switzerland.
“We believe that CrtN is a novel drug target for the virulence factor-based therapy against S. aureus,” said Gao. “Our approach of employing non-antibiotic drugs to treat MRSA infections by disarming the defensive shield of invading pathogens has offered new hope and new strategies for the treatment of bacterial infections related to multidrug resistant pathogens.”
The article can be found at: Gao et al. (2017) Dehydrosqualene Desaturase as a Novel Target for Anti-Virulence Therapy against Staphylococcus aureus.
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Source: University of Hong Kong.
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