Strep. That tickle that turns your throat sore and you wake up hoping you’re imagining it. Well, you have Streptococcus pyogenes, also known as Group A Streptococcus (GAS) to thank for that. According to the La Jolla Institute for Immunology, 600 million people contract strep throat worldwide, a large number of them being children. Fortunately, strep can be easily treated with a prescription for antibiotics, but unfortunately, GAS is much more complex than just a sore throat.
Ouchie!
This bacterium is responsible for quite a few diseases ranging from relatively mild tonsillopharyngitis (strep throat) to life-threatening conditions like toxic shock syndrome (TSS), necrotizing fasciitis, cellulitis, pneumonia, and sepsis. Yes, necrotizing fasciitis is the “flesh eating disease”. S. pyogenes can play many, many roles in the human body. Sometimes it may even appear harmless at first, only to later cause severe complications. These complications can include invasive infections like peritonsillar abscesses, or post-infection immune-mediated diseases like scarlet fever or post-streptococcal glomerulonephritis. Even with the decades of research on this pathogen, she still continues to surprise scientists.
^ Our dear Streptococcus pyogenes bacterium ^
Exploring how this bacterium is evolving at the molecular level and understanding how this evolution occurs is key to human health and the future of vaccine development. By examining the genetic makeup of 70 bacterial samples collected from hospitalized patients, researchers reveal how subtle genetic differences can influence disease severity and antibiotic resistance.
So, what makes S. pyogenes such a successful pathogen? It has an extensive collection of virulence factors, which are molecular tools that help bacteria infect, survive, and spread within a host. Some of these virulence factors are attached directly to the bacterial cell wall, helping the organism adhere to host tissue. Think of these as molecular Velcro, helping it attach to the host cell. Other virulence factors are secreted into the surrounding environment, allowing the bacteria to break down tissue. Like secret agents, they weaken defense and “open the door” for invasion: the bacteria evades immune defenses and spreads deeper into the body.
One of the major virulence factors is M protein, which is found on the surface of the bacterium. The M protein helps S. pyogenes avoid detection by our immune system; it also aids with adhesion, allowing bacteria to stick to host cells and establish infection.
M protein is encoded by the emm gene and it comes in many different variations, known as emm types. These variations are important because different emm types are associated with different disease outcomes: some are more likely to cause mild infections (like emm4), while others (like emm1) are linked to severe or invasive disease. The reason for their diversity is horizontal gene transfer, the movement of genetic material between bacteria. Horizontal gene transfer is like bacteria sharing survival tips directly with each other which allows them to quickly gain new “abilities.” This allows S. pyogenes to rapidly acquire new traits, including antibiotic resistance. Through recombination and genetic exchange, new emm variants can emerge that are better adapted to survive in changing environments, even with the introduction of antibiotics. Since M protein plays such a central role in infection, many experimental vaccines are designed to target it. However, the high variability of emm types presents a challenge because a vaccine effective against one strain may not protect against another.
To examine just how S. pyogenes is changing, researchers analyzed bacterial isolates collected from hospitalized patients between 2023 and 2024. The samples were taken from a variety of infection types, including skin and soft tissue infections (SSTIs), pneumonia, peritonsillar abscesses, and perianal abscesses. By sequencing the emm gene of each isolate, 12 different emm types were identified across 8 genetic clusters. The figure below visualizes the distribution of emm types.
Figure 1. n = percent of specific infection type for each emm-type (Muhtarova et al., 2025)
It may look complicated, but when you break it down it becomes easier to understand. Each bar represents a different emm type and each color represents a type of infection. The chart is basically just showing us that the most common types were emm1, emm3, emm4, emm11, and emm28. There was significant genetic diversity even within these common types, emphasizing how adaptable this bacterium really can be. Interestingly enough, different emm types also appeared more frequently in certain infection categories, which suggest that certain genetic variants of S. pyogenes may be better equipped to infect specific tissue or perhaps cause particular types of disease. The biggest variations between emm types lie in the N-terminal region of the protein (Friães et al., 2019), this is the part exposed to the host (our) immune system. This changes how the bacteria attach to cells and avoid the immune system. This is why some emm types (emm1 and emm3) are more likely to cause severe/invasive infections, while others typically cause a milder, more localized infection like abscesses.
Another interesting finding of this study was the comparison between the current isolates (2023-2024) and data collected Pre-COVID (2014-2018). There has been a shift in the prevalence of certain emm types. In particular, emm1 has become more prevalent in recent isolates compared to pre-COVID isolates. This is important because these emm1 strains give rise to more severe and invasive infections. On the other hand, emm4 is linked to milder disease outcomes and is still present.
What could be driving this increase of prevalence? As mentioned previously, isolates were taken before and after the COVID-19 pandemic. Our behavior as a society and the use of antibiotics may have changed what bacterial strains are circulating. With social distancing and masks, people in society were interacting less and reshaping transmission patterns. Once our interactions return closer to normal, strains that are better at spreading or causing more severe disease (like emm1) may be working harder. This shows society that pathogens are constantly evolving and responding to changes in our environment and behavior.
The researchers of this study also investigated antibiotic resistance patterns which are crucial for treating diseases that arise. The good news: all 70 isolates remained susceptible to the antibiotics penicillin G and linezolid. This consistency is reassuring from a treatment POV, especially in a time where antibiotic resistance is a concern that is growing. According to the American Society for Microbiology, as strains of GAS become less susceptible to commonly used antibiotics, there would be a large impact on children around the world as 5-15 year olds are the most susceptible to strep throat.
However, when looking at other antibiotics, these results vary. Antibiotic resistance was observed in 14.3% of isolates for macrolides and lincosamides and 18.6% for tetracyclines. These antibiotics are especially important for patients who are allergic to penicillin and resistance to these could limit treatment options for some. Most of these strains were isolated from skin and soft tissue infections (SSTIs), showing that these environments may be places where resistant strains thrive. Delving deeper, researchers found that all resistant strains carried the ermB gene. This gene works by changing the bacterial ribosome, and essentially preventing the antibiotic from binding effectively. Like changing the lock so the key no longer fits! Similarly, isolates that were resistant to tetracycline were found to be positive for the tetM and tetO genes. These results show that genetic elements directly affect clinical outcomes.
Picture from Words of Friends
Weirdly enough, the study also noted a decrease in overall macrolide resistance compared to previous years which is linked to a lower prevalence of the emm28 strain, typically associated with the ermB resistance gene. Bacterial evolution has an ever-changing dynamic between strain prevalence and patterns of antibiotic resistance.
One of the biggest takeaways from this study is that not all S. pyogenes are created equal. The emm type can cause some strains to be easily treatable and somewhat harmless, and others to be much more severe. For researchers, these findings show the challenges that are faced with developing vaccines. Emm types can directly impact vaccine outcomes by how antibodies can identify and neutralize bacteria. For clinicians, looking deeper into emm types can help make more effective decisions regarding treatment.
In terms of limitations of this study, it included data that was collected from two university hospitals located in two cities within a relatively short period due to the COVID-19 pandemic. Some of the collected specimens (perianal abscesses) were limited in numbers, but the results disclose the emm-types associated with them and allow comparison with data from other studies. Other limitations are the absence of isolates from blood culture and the fact that we do not specifically investigate the presence of the M1 UK genetic variant, which is a rapidly expanding genetic lineage of S. pyogenes.
Despite these limitations, this study applies modern techniques to research antibiotic susceptibility in isolates from patients. They also state that this deepens current understanding of more severe GAS infections and its continued monitoring.
This study gave us a snapshot in time of a pathogen that is constantly evolving. It can be responsible for a large range of symptoms, and can even cause serious disease. By continuing to track its resistance patterns and evolution of genetics, physicians can guide more accurate treatment and us microbiologists can better understand the complexity behind casually mentioned conditions like “strep throat.”
Citations:
Friães, A., Melo-Cristino, J., Ramirez, M. et al. Changes in emm types and superantigen gene content of Streptococcus pyogenes causing invasive infections in Portugal. Sci Rep 9, 18051 (2019). https://doi.org/10.1038/s41598-019-54409-2
Muhtarova, A. A., Boyanov, V. S., Alexandrova, A. S., & Gergova, R. T. (2025). Molecular Characterization of Streptococcus pyogenes Isolates Recovered from Hospitalized Patients During the Years 2023-2024. Microorganisms, 13(9), 2148. https://doi.org/10.3390/microorganisms13092148
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