Scientists at the Hebrew University of Jerusalem’s Faculty of Medicine say they have found out how Streptococcus pyogenes, ordinarily benign to mildly infectious, turns virulent and causes necrotizing fasciitis, i.e., flesh-eating disease. The team believes their finding opens up the path to possible future treatments to curb this and other potentially fatal bacteria.
S. pyogenes, also known as Group A streptococcus (GAS), reportedly is responsible for 500,000 deaths worldwide. The flesh-eating disease, in particular, is an extremely vicious infection that progresses rapidly throughout the soft tissues of the body, often leaving doctors with little time to stop or delay its progress. The main treatments include administration of antibiotics and surgical removal of infected tissues. Yet despite prompt treatment, the bacteria disseminate and cause death in approximately 25% of patients.
The research group, which reported their study (“An Extracellular Bacterial Pathogen Modulates Host Metabolism to Regulate Its Own Sensing and Proliferation”) in Cell, discovered a novel mechanism that influences GAS virulence at the early steps of the infection. They noticed that when GAS adheres and infects the host’s cells, it delivers two streptolysin toxins into these cells. These toxins interfere with the body’s mechanism for quality control of protein synthesis. This in turn triggers a defensive stress response, which increases the production of the amino acid asparagine (ASN).
“The released ASN is sensed by the bacteria, altering the expression of ∼17% of GAS genes of which about one-third are dependent on the two-component system TrxSR. The expression of the streptolysin toxins is strongly upregulated, whereas genes linked to proliferation are downregulated in ASN absence,” write the investigators. “Asparaginase, a widely used chemotherapeutic agent, arrests GAS growth in human blood and blocks GAS proliferation in a mouse model of human bacteremia. These results delineate a pathogenic pathway and propose a therapeutic strategy against 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 new and more effective treatments against infectious diseases, concluded the scientists.