Q&A: Understanding the ‘secret life’ of group A streptococcus

James M. Musser, MD
James M. Musser

Researchers repurposed a genetic tool first used for streptococcal pharyngitis in horses to learn more about flesh-eating bacteria in humans.

They focused on necrotizing myositis, which is commonly caused by group A streptococcus. The disease attacks muscle, killing up to 50% of patients, and often leaves survivors with deformities and missing limbs.

Infectious Disease News spoke with James M. Musser, MD, PhD, chair of the department of pathology and genomic medicine at Houston Methodist Hospital, about the findings and how the results may impact clinical outcomes. – by Marley Ghizzone

What prompted the use of a tool originally meant to detect strep throat in horses?

We used a technique called TraDIS, which is a technique originally applied to an organism called Streptococcus equi that is sort of a cousin to group A streptococcus. It is a really interesting pathogen of horses that causes a disease called strangles, which is like a severe strep throat infection in horses. It is a very new technique that has only recently been applied to a small number of other pathogens.

Our collaborator, Andrew Waller with the animal health trust in the United Kingdom, which developed TraDIS, used it for the Streptococcus equi studies in horses. We had already worked with him once before on a previous study where we identified new genes linked to how group A streptococcus survives in human saliva. Several other investigators around the world also have used this tool in bacterial pathogens that are of interest to them, but no one has ever done it in group A streptococcus before. Our lab is the first to use this in group A streptococcus.

How did you and your team repurpose this tool, and how does it work?

TraDIS is a special genetic tool that permits us to very rapidly one by one inactivate every gene in the group A streptococcus genome. So, we were able to hone in on the crucial genes responsible for causing or contributing to group A streptococcus necrotizing myositis in humans.

Fortunately, we did not have to adapt it that much for use in group A streptococcus. It turns out to be a very effective tool in diagnosing many different bacterial pathogens, regardless of whether it is group A streptococcus, Streptococcus equi or other pathogens. You can think of it as a Swiss Army knife of genetic techniques.

Why did you choose to assess group A streptococcus?

We really wanted to focus on a devastating human infection with a very high mortality rate, and that is why we studied this type of group A streptococcus disease, necrotizing myositis. Many members of the public know it simply as flesh-eating disease. Fortunately, it is not that common, but when it occurs, up to about one-half of all humans that develop it will die.

What were the major takeaway findings about group A streptococcus?

Several of the new discoveries we made in this paper include an in-depth understanding of the precise genes that group A streptococcus is using to cause necrotizing myositis. We were able to really dissect and unveil the secret life of group A streptococcus and how it is causing severe disease while living in muscle. We call this identifying the secret life of group A streptococcus, because before this work was done, we really did not understand the full range of different genes that were contributing to this very severe infection.

It also permitted us to identify one group of specialized genes that we call transporters. These transporters are responsible for bringing nutrients into the bacterial cell that permit it to survive and thrive in places where we do not want it to be, such as in the muscle of humans. This understanding that transporters in the group A streptococcus contribute extensively to this disease in humans was a key discovery. Before this study was done, we really did not know these transporter genes were so important in causing the flesh-eating disease. The critical importance of transporter genes was very unexpected.

One of the other unexpected findings from our study was that we were able to identify certain genes that, when inactivated, actually cause a more severe disease, and we are doing further research on that set of genes.

We thought we were going to identify certain other aspects of group A streptococcus that were responsible for the disease.

Can these findings improve clinical outcomes? Why or why not?

One of the crucial things our study permits us to do is that now by understanding the genetic roadmap of how group A streptococcus causes the flesh-eating disease, we can use that crucial information to then begin to develop new strategies to prevent it, to make better treatments for our patients and then, ultimately, create an effective vaccine against group A streptococcus.

We now understand precisely what high-value targets we should be going after and can figure out how to destroy them.

Imagine in any organism or pathogen that causes disease that you could now have in front of you — a full listing of the genes that are contributing. That is a very important tool against the fight to create better vaccines and new therapies, and to, perhaps, really wipe this organism off the face of the earth.

Reference:

Zhu L, et al. J Clin Invest. 2019;doi:10.1172/JCI124994.

Disclosure: Musser reports no relevant financial disclosures.

James M. Musser, MD
James M. Musser

Researchers repurposed a genetic tool first used for streptococcal pharyngitis in horses to learn more about flesh-eating bacteria in humans.

They focused on necrotizing myositis, which is commonly caused by group A streptococcus. The disease attacks muscle, killing up to 50% of patients, and often leaves survivors with deformities and missing limbs.

Infectious Disease News spoke with James M. Musser, MD, PhD, chair of the department of pathology and genomic medicine at Houston Methodist Hospital, about the findings and how the results may impact clinical outcomes. – by Marley Ghizzone

What prompted the use of a tool originally meant to detect strep throat in horses?

We used a technique called TraDIS, which is a technique originally applied to an organism called Streptococcus equi that is sort of a cousin to group A streptococcus. It is a really interesting pathogen of horses that causes a disease called strangles, which is like a severe strep throat infection in horses. It is a very new technique that has only recently been applied to a small number of other pathogens.

Our collaborator, Andrew Waller with the animal health trust in the United Kingdom, which developed TraDIS, used it for the Streptococcus equi studies in horses. We had already worked with him once before on a previous study where we identified new genes linked to how group A streptococcus survives in human saliva. Several other investigators around the world also have used this tool in bacterial pathogens that are of interest to them, but no one has ever done it in group A streptococcus before. Our lab is the first to use this in group A streptococcus.

How did you and your team repurpose this tool, and how does it work?

TraDIS is a special genetic tool that permits us to very rapidly one by one inactivate every gene in the group A streptococcus genome. So, we were able to hone in on the crucial genes responsible for causing or contributing to group A streptococcus necrotizing myositis in humans.

Fortunately, we did not have to adapt it that much for use in group A streptococcus. It turns out to be a very effective tool in diagnosing many different bacterial pathogens, regardless of whether it is group A streptococcus, Streptococcus equi or other pathogens. You can think of it as a Swiss Army knife of genetic techniques.

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Why did you choose to assess group A streptococcus?

We really wanted to focus on a devastating human infection with a very high mortality rate, and that is why we studied this type of group A streptococcus disease, necrotizing myositis. Many members of the public know it simply as flesh-eating disease. Fortunately, it is not that common, but when it occurs, up to about one-half of all humans that develop it will die.

What were the major takeaway findings about group A streptococcus?

Several of the new discoveries we made in this paper include an in-depth understanding of the precise genes that group A streptococcus is using to cause necrotizing myositis. We were able to really dissect and unveil the secret life of group A streptococcus and how it is causing severe disease while living in muscle. We call this identifying the secret life of group A streptococcus, because before this work was done, we really did not understand the full range of different genes that were contributing to this very severe infection.

It also permitted us to identify one group of specialized genes that we call transporters. These transporters are responsible for bringing nutrients into the bacterial cell that permit it to survive and thrive in places where we do not want it to be, such as in the muscle of humans. This understanding that transporters in the group A streptococcus contribute extensively to this disease in humans was a key discovery. Before this study was done, we really did not know these transporter genes were so important in causing the flesh-eating disease. The critical importance of transporter genes was very unexpected.

One of the other unexpected findings from our study was that we were able to identify certain genes that, when inactivated, actually cause a more severe disease, and we are doing further research on that set of genes.

We thought we were going to identify certain other aspects of group A streptococcus that were responsible for the disease.

Can these findings improve clinical outcomes? Why or why not?

One of the crucial things our study permits us to do is that now by understanding the genetic roadmap of how group A streptococcus causes the flesh-eating disease, we can use that crucial information to then begin to develop new strategies to prevent it, to make better treatments for our patients and then, ultimately, create an effective vaccine against group A streptococcus.

We now understand precisely what high-value targets we should be going after and can figure out how to destroy them.

Imagine in any organism or pathogen that causes disease that you could now have in front of you — a full listing of the genes that are contributing. That is a very important tool against the fight to create better vaccines and new therapies, and to, perhaps, really wipe this organism off the face of the earth.

Reference:

Zhu L, et al. J Clin Invest. 2019;doi:10.1172/JCI124994.

Disclosure: Musser reports no relevant financial disclosures.