Novel Toxin Contributes to Severe Group A Streptococcus Flesh-eating Infections


Research published this week in the Proceedings of the National Academy of Science USA shows that a novel toxin resembling a snake venom poison contributes to severe group A Streptococcus flesh-eating infections. This discovery provides promise for the development of new therapies to treat some forms of these life-threatening infections.

Research conducted by James M. Musser, MD, PhD, co-director of the Methodist Hospital Research Institute and senior author of the paper, found that a pathogen enzyme called secreted phospholipase A2 (SlaA) kills human cells and helps the germ to spread throughout the body. Importantly, immunization of laboratory mice with a vaccine prepared from this enzyme conferred protection from invasive strep infections. These results identified SlaA as a target for new therapeutics. The study was done in collaboration with scientists at Harvard Medical School and Southwest Foundation for Biomedical Research in San Antonio.

Strep throat affects more than 600 million people globally each year, and necrotizing fasciitis, also known as the flesh eater, causes debilitating and deadly invasive infections. Necrotizing fasciitis affects thousands of people each year in the U.S. and is associated with mortality rates as high as 50 percent.

Mussers lab focuses on understanding how toxins made by the highly-contagious pathogen help the germ to grow in the body during infections. By understanding this process, they seek to identify new strategies to treat life-threatening infections and develop vaccines to prevent them.

Several years ago, Mussers group sequenced the genome of a highly virulent strain of group A strep and discovered that it secreted the novel SlaA protein, which is related to a potent snake venom toxin. Surprisingly, they discovered that SlaA was made by a virus that had infected the strep strain. They hypothesized that SlaA production gave this strain an advantage, allowing it to infect efficiently, spread rapidly and cause unusually severe infections. Their studies suggested that acquiring this SlaA-producing virus was a pivotal event in the creation of an unusually virulent strain that has risen to prominence.

To take this research further, Mussers group made a mutant strep strain that no longer secreted SlaA and studied it in several infection models. Their research showed that inactivating the SlaA gene produced a far less virulent strep strain. In addition, animals given a vaccine based on SlaA were protected against severe strep disease. Finally, it was shown that SlaA was required for effective infection of throat. Mussers group is continuing to characterize the effect of SlaA on human cells with the goal of developing new therapies that target and neutralize this toxin, thereby lessening the severity of strep disease.

The work solves an important puzzle in group A Streptococcus pathogenesis, and is a crucial step toward the development of new treatments for necrotizing fasciitis, stated Dr. Frank DeLeo from the National Institutes of Allergy and Infectious Diseases, a scientist not involved with the study.

Source: Methodist Hospital, Houston    


Related Videos
An eye instrument holding an intraocular lens for cataract surgery. How to clean and sterilize it appropriately?   (Adobe Stock 417326809By Mohammed)
Christopher Reid, PhD  (Photo courtesy of Christopher Reid, PhD)
Paper with words antimicrobial resistance (AMR) and glasses.   (Adobe Stock 126570978 by Vitalii Vodolazskyi)
3D illustration: Candida auris   (Adobe Stock 635576411 By Niamh )
 MIS-C (Adobe Stock 350657530 by Bernard Chantal)
Set of white bottles with cleaning liquids on the white background. (Adobe Stock 6338071172112 by zolnierek)
Medical investigators going over data. (AdobeStock 589197902 by Wasan)
CDC logo is seen on a laptop. (Adobe Stock 428450603 by monticellllo)
Association for the Health Care Environment (Logo used with permission)
Related Content