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Hebrew University Faculty of Medicine Scientist Reveals Initial Steps Leading to the Development of Flesh-Eating Diseases

 Research opens way to possible new treatments for bacterial infections  How does Streptococcus pyogenes, or Group A streptococcus (GAS) -- a bacterial pathogen that can colonize humans without causing any symptoms or just mild infections -- also cause life-threatening diseases such as necrotizing fasciitis (commonly known as flesh-eating disease) and streptococcal toxic shock syndrome?This is a mystery which has intrigued many researchers in the field. Now, Hebrew University of Jerusalem Faculty of Medicine researchers have discovered the mechanism whereby this bacterium turns deadly, opening the door to possible promising future treatments to curb this and other potentially fatal bacteria.  Annually, GAS infections lead worldwide to approximately 160,000 deaths and severe injuries to those infected. The flesh-eating disease, in particular, is 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. Despite prompt treatments, bacteria succeed to disseminate and cause death in approximately 25% of patients.In probing the ways in which GAS progresses, Prof. Emanuel Hanski of the Institute of Medical Research Israel Canada at the Hebrew University Faculty of Medicine, together with Ph.D. student Moshe Baruch and an international research team, discovered a novel mechanism that influences GAS virulence at the early steps of the infection. The results of their study were published this week in the scientific journal Cell.They found that when GAS adheres and infects the host’s cells, it delivers into these cells two streptolysin toxins. These toxins impair the mechanism responsible in the host for quality control of protein synthesis. This in turn triggers a defensive 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– and potentially deadly -- rate of proliferation.The research team further significantly discovered that asparaginase, a protein that digests asparagine and is a widely-used chemotherapeutic agent against leukemia, arrests GAS growth in human blood and in a mouse model of human bacterial infection. Asparginase has never before been attempted as a mean to treat GAS infections. In this case and perhaps in others, 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 new and more effective treatments against infectious diseases.