New Finding May Help Prevent Flesh-eating Group A Streptococcus Infections

A recent discovery by researchers at Houston Methodist Hospital may offer a new way to prevent and treat Group A Streptococcus infections, including deadly flesh-eating necrotizing fasciitis infections.

Group A strep bacteria cause a range of infections, from less severe cases of strep throat, scarlet fever, and impetigo to more serious conditions such as necrotizing fasciitis, a rare but deadly soft tissue infection that can spread quickly in the body. According to the Centers for Disease Control and Prevention (CDC), there are as many as 13,000 cases of invasive group A strep disease in the United States each year, including cellulitis with blood infection, pneumonia, and necrotizing fasciitis, causing 1,100 and 1,600 deaths. In fact, in recent news, a woman in Houston died of necrotizing fasciitis after becoming exposed to contaminated floodwater following Hurricane Harvey. Non-invasive group A strep infections—such as strep throat and impetigo—number in the millions each year, and while highly contagious, they are typically easy-to-treat with antibiotics such as penicillin or amoxicillin.

A new study published in the journal the Proceedings of the National Academy of Sciences details recent findings of a research team from Houston Methodist Hospital. Nearly a century ago, researchers discovered that during infection, strains of streptococci produce streptococcal pyrogenic exotoxin B (SpeB), a secreted cysteine protease responsible for causing the telltale fever and rash associated with scarlet fever, and also key to the development of necrotizing fasciitis. However, in the new paper, the study team notes that prior to their investigation the molecular basis for growth phase control of SpeB gene expression was unknown. Lead investigator Muthiah Kumaraswami, PhD, and his team found that group A strep bacteria secrete a peptide that then signals neighboring bacteria to produce SpeB. The discovery may lead to the development of new antibiotics or a vaccine to trigger the production of antibodies that can target the peptide signal or block the signal and interfere with toxin production.

While group strep A bacteria have not exhibited the antibiotic resistance of so many of today’s “superbugs,” a new antibiotic developed based on these findings could, in a sense, be resistance-proof. “Antibiotic resistance occurs, in most cases, when you target the fundamental cellular processes that are essential for bacterial growth,” such as DNA synthesis, protein synthesis, and cell wall synthesis, explained Dr. Kumaraswami in an interview with Contagion ^®. “Since these processes are critical for bacterial viability, the selection pressure on the bacteria is high to introduce mutations in the antibiotic targets to avoid antibiotic drug-induced cytotoxicity. On the other hand, the peptide communication pathway is not essential for bacterial survival, however, it is required for the disease pathogenesis. Thus, any interference strategies targeting the virulence regulatory pathways are likely to place less selection pressure on the pathogen, thereby reduced the frequency of mutations and resistance. Although these arguments provide a strong rationale for the reduced occurrence of resistance, it still needs to be tested.”

On the tail of these findings, Dr. Kumaraswami says that similar peptide signals may be discovered in other gram-positive bacterial human pathogens, such as Streptococcus pneumoniae (pneumococci), Staphylococcus aureus, group B streptococcus, and Enterococcus faecalis. “Our current work is primarily focused on group A streptococcus, flesh-eating bacteria, and we don't plan on expanding into other pathogens in the short term,” says Dr. Kumaraswami, noting the potential for further research. “Our goal is to continue elucidating different components of this crucial signaling pathway and to evaluate the translation potential of this pathway toward vaccine or antimicrobial development.

Feature Picture: A three-dimensional (3D) computer-generated image of a group of erythromycin-resistant Group-A Streptococcus (GAS), also known as S. pyogenes, bacteria, which were arranged in chains. Picture Feature Source: James Archer / Centers for Disease Control and Prevention.