the secret life of flesh-eating bacteria

With the aid of a tool used for the first time in strep throat in horses, Methodist researchers in Houston unveiled the secret life of flesh-eating bacteria and showed how it causes a serious illness while living deep in the muscles.

The team focused on necrotizing myositis, a devastating human infection with a very high mortality rate. Caused by a group A streptococcus, this flesh-flesh disease attacks the muscle, causing death up to 50% of the time and often leaves the survivors with serious deformities and missing limbs.

"We call this identification of the secret life of group A streptococcus because, before the realization of this new work, we did not really understand the whole spectrum of genes that contributed to this terrible infection," he said. said James M. Musser, MD, Ph.D., president of the Department of Pathology and Genomic Medicine at Houston Methodist. "We were able to carefully dissect and draw the curtain to identify what allowed this organism to cause a serious muscle disease, the so-called flesh disease. We now understand precisely the goals of great value that we should aim to disable or destroy. "

Musser is the corresponding author of an article published online Jan. 22 and printed Feb. 1 in the Journal of Clinical Investigation, entitled "Landscape of the Group A Streptococcal Gene Disease during the course of the year. necrotizing myositis ". Musser says his team now has a thorough understanding of the precise genes used by Group A streptococcus to cause this deadly infection in the muscles.

"We used a special genetic tool that allowed us to rapidly inactivate each of the genes in the group A streptococcus genome one by one, allowing us to target the essential genes responsible for the necrotizing myositis of group A streptococcus." Says Musser. "Using this tool, we identified 72 of the 1,800 cluster A strep genes as key genes in the new target for the development of new vaccines and antibiotics that are effective against this disease. So, in one experiment, it allowed us to identify all the important genes for this bacterium to infect the muscle. "

The technique used, called TraDIS, is a powerful genetic tool used in horses. It was first applied to an organism that is a cousin of the human strep throat called Streptococcus equi, a pathogen responsible for an infection similar to the strangulation of the lymphadenopathy. severe strep throat in horses.

"We now have a genetic roadmap explaining how group A streptococcus is causing this flesh disease. We can leverage this critical information to begin developing new disease prevention strategies, improve treatments for our patients, and hopefully create an effective vaccine against Group A Streptococcus that will eventually eliminate this organism from the surface. of the globe. "

Used by scientists at Animal Health Trust, a British charity specializing in scientific and veterinary research, this new technique has only recently been applied to a small number of other pathogens, with Musser's laboratory being the first for use in group A streptococci.

Musser's British collaborator, Andrew Waller, PhD, responsible for bacteriology at Animal Health Trust, used TraDIS for studies on horses and explains that the Houston Methodist Research Institute team did not need to Adapt the tool to such extensive use for group A streptococcus, since the strangles bacterium is more than 80% identical to group A streptococcus in humans. According to him, it has proven to be an effective tool against many bacterial pathogens, giving scientists a complete list of genes contributing to deadly organisms.

"One key finding was the discovery of a group A gene family of genes known as transporters, responsible for the delivery of nutrients into the bacterial cell, allowing it to survive and thrive in places where we do not want it, for example human muscle, "said Musser. "This understanding of the fact that transporters largely contribute to this serious invasive disease in humans was very unexpected. Before the end of this study, we did not really know that these transport genes were so important for causing flesh disease.

Luchang Zhu, Randall J. Olsen, Stephen B. Beres, Jesus M. Eraso, Matthew Ojeda Saavedra, Samantha L. Kubiak, Concepcion C. Cantu, and Leslie Jenkins of the Houston Methodist Research Institute; and Amelia R.L. Charbonneau and Andrew S. Waller of Animal Health Trust and the University of Cambridge in the United Kingdom.

The work was funded by the Fondren Foundation and the UK Council for Research in Biotechnology and Biological Sciences (reference 1503883).

Source: Houston Methodist