NUS-HUJ-CREATE researchers discover an FDA-approved drug that can stop flesh-eating bacteria


Collaboration between the National University of Singapore (NUS) and Hebrew University of Jerusalem (HUJ) on inflammation research may lead to a potential treatment for deadly bacterial infections

Scientists from the NUS-HUJ-CREATE Inflammation Research Programme found that the enzyme which degrade the amino acid asparagine (asparaginase -ASNASE) – and serves as a common chemotherapeutic agent – arrests Group A Streptococcus (GAS) growth in human blood and blocks bacteria's proliferation, thus initiating a new potential treatment against deadly Streptococcal infections. GAS is a strict human pathogen that causes a wide range of infections, from mild to deadly. It can colonise the host without causing any symptoms, or cause mild infections of skin and trough such as pharyngitis. On the invasive end of the spectrum, GAS can cause life-threatening infections such as bacteremia, necrotising fasciitis (commonly known as flesh-eating disease), and streptococcal toxic shock syndrome. The flesh-eating bacterium, in particular, causes an extremely vicious infection which progresses rapidly throughout the soft tissues of the body, often leaving doctors with little time to stop or delay the progress of the infection. The main treatments include administration of antibiotics and surgical removal of infected tissues. How GAS converts from benign coloniser of the human to a deadly one has intrigued many researchers in the field.

To decipher this mystery, an international research team led by Professor Emanuel Hanski of HUJ, together with NUS Research Fellows Dr Zhou Yiting and Dr Catherine Cheng Youting, discovered a novel mechanism that influences GAS virulence at the early steps of the infection. Prof Hanski and the NUS-HUJ-CREATE team found that GAS is able to directly alter the host's metabolism for its own benefit. When GAS adheres and infects the host's cells, it delivers two streptolysin toxins – streptolysin O and streptolysin S – into these cells. These toxins impair the mechanism responsible in the host for quality control of protein synthesis. This in turn triggers a stress response, which among other things also increases the production of the amino acid asparagine. GAS senses the increased asparagine level and alters its gene expression profile. GAS also utilises this amino acid to increase its rate of proliferation. The research team further discovered that asparaginase, a widely-used chemotherapeutic agent, arrests GAS growth in human blood and in a mouse model of human bacteremia, thus suggesting the potential use of asparaginase as a new therapeutic agent against GAS. Asparaginase is an FDA approved drug for lymphoblastoid leukemia, and has never before been applied to treat GAS infections.

The findings of this study constitute a major advance of the concept that understanding the metabolic changes occurring between the pathogen and its host during infection can lead to development of effective treatments against infectious diseases. For more information about the topic, read the article published in Cell and interview with the researcher.

 

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