Strep Throat: Rising Antibiotic Resistance & New Bacterial Threat in France

A collaborative research effort has revealed a concerning trend: a potential decrease in the effectiveness of common antibiotics against a globally significant bacterial pathogen, Streptococcus pyogenes. This bacterium, responsible for an estimated 500,000 deaths annually worldwide, is increasingly showing signs of resistance, raising public health concerns about future treatment options.

The research, stemming from work initiated in 2009 at the University Hospital of Rennes in France, highlights the importance of ongoing surveillance of antibiotic resistance. Understanding how bacteria evolve and adapt is crucial for maintaining effective treatments against infectious diseases.

Streptococcus pyogenes, first identified long before the germ theory of disease was fully understood, is a bacterium that exclusively infects humans. As early as 1847, physician Ignace Semmelweis suspected an “invisible agent” transmitted by doctors’ hands was responsible for severe infections in women after childbirth, a prescient observation that foreshadowed the discovery of bacteria. Today, we know that agent was Streptococcus pyogenes.

“Streptococcus pyogenes,” Responsible for 500,000 Deaths Annually Worldwide

While the bacterium can reside in the throat or on the skin without causing illness, it can also lead to a range of conditions, from relatively mild infections like strep throat to life-threatening complications if left untreated. The World Health Organization (WHO) estimates that 700 million infections occur globally each year due to this bacterium, with 600 million specifically affecting the throat. Approximately 500,000 people die annually from these infections, making it one of the top ten leading causes of death worldwide.

Currently, Streptococcus pyogenes is generally susceptible to antibiotics, particularly penicillins, which belong to the beta-lactam family. Beta-lactams work by blocking essential proteins the bacteria need to survive, ultimately preventing them from multiplying. However, researchers are now observing changes that could undermine this effectiveness.

A Sensitivity to Penicillins That Risks Not Lasting

The target of beta-lactam antibiotics is a specific protein called PLP (penicillin-binding protein), vital for building the bacteria’s protective cell wall. When the antibiotic binds to PLP, it disables the protein, leading to bacterial death. However, mutations in the gene coding for PLP can reduce the antibiotic’s ability to bind, potentially leading to antibiotic resistance – a phenomenon already seen in other streptococcal species like Streptococcus pneumoniae.

Because Streptococcus pyogenes has historically been reliably susceptible to beta-lactams, antibiotic susceptibility testing (antibiograms) isn’t always performed before treatment. Recent reports, however, indicate a diminution in sensitivity to beta-lactams in some strains, potentially due to mutations in the PLP protein. These mutations may be driven by inappropriate antibiotic use, such as insufficient dosages or inconsistent patient adherence to treatment regimens.

A Collection of Streptococci from Patients at the CHU de Rennes

Researchers at the CHU Ponchaillou-University of Rennes began systematically collecting samples of this bacterium, alongside a closely related species, Streptococcus dysgalactiae subspecies equisimilis (SDSE), from patients in the Ille-et-Vilaine region of France as early as 2009. This proactive approach allowed them to detail the evolution of infections caused by the bacteria over a decade.

This work fostered a collaboration with Dr. James Musser, a global expert on Streptococcus pyogenes at Houston’s Baylor College of Medicine. Analyzing the genes of all collected strains revealed that Streptococcus pyogenes frequently incorporates DNA fragments from SDSE. More concerningly, these genetic exchanges were found to alter the PLP protein in S. pyogenes, reducing its susceptibility to several beta-lactam antibiotics.

This discovery serves as a warning, suggesting that antibiotic resistance in Streptococcus pyogenes may be underestimated and could spread further. Maintaining continuous monitoring is essential to quickly detect resistant bacteria and prevent a public health crisis.

SDSE, a Little-Known Species Not to Be Underestimated

Researchers also focused on the SDSE samples collected alongside those of Streptococcus pyogenes. In recent years, teams worldwide have reported a surprising increase in severe infections caused by SDSE, likely due to the spread of a particular strain (stG62647). Previously considered a harmless resident of the skin or throat, SDSE is now recognized as a potential source of serious infections.

The collaborative Franco-American team genetically analyzed approximately 500 samples collected in Rennes, pinpointing the first detection of the stG62647 strain to 2013 and its rapid spread throughout the Ille-et-Vilaine region. This strain is genetically homogenous, indicating it recently descended from a common ancestor particularly well-adapted to infecting humans.

The Severity of Infection Linked to Patient Characteristics

Laboratory studies aimed at understanding the infection process of SDSE revealed the complexity of its virulence mechanisms. Researchers also observed a paradox: despite their genetic similarity, SDSE strains exhibit varying levels of danger (virulence). This suggests that the severity of infection depends on complex regulatory mechanisms within the bacteria, and how it interacts with the infected individual.

In other words, the severity of the infection isn’t solely determined by the bacteria itself, but also by the unique characteristics of each person infected, as detailed in their latest publication on the subject.

Important Implications for Public Health

Building on their experience with S. pyogenes, these pioneering studies on SDSE reveal that many secrets remain to be uncovered about both bacteria. However, the results already have important implications for:

• improved diagnosis and monitoring of antibiotic resistance, requiring laboratories to be more vigilant in detecting resistant strains;

• continuous surveillance of infections to prevent the emergence of new, virulent bacterial clones;

• the development of new treatments, as understanding virulence mechanisms opens the door to new therapeutic targets and potential vaccine approaches.

A Model of Effective Collaborative Research for Health

This Franco-American collaboration demonstrates the value of combining different approaches – field surveillance, genetic analysis, gene expression studies, and laboratory testing. The researchers have made the genetic data of the Breton strains available to the international scientific community, facilitating future research on these bacteria of growing public health interest. This “translational” research – moving from the lab to the patient – is highly effective for anticipating future infectious disease crises and adapting prevention and treatment strategies to the constant evolution of pathogens.