Group A streptococcal myonecrosis: increased vimentin expression after skeletal-muscle injury mediates the binding of

Amy E Bryant1, Clifford R Bayer, Jeremy D Huntington

  • 1Veterans Affairs Medical Center, Boise, Idaho 83702, USA. amy.bryant@mindspring.com

Insights

Group A Streptococcus (GAS) causes severe myonecrosis by binding to vimentin, a protein upregulated on injured muscle cells. This explains how GAS infections develop at minor injury sites, paving the way for new therapies.

Area of Science:

  • Microbiology
  • Cell Biology
  • Pathology

Background:

  • Invasive group A streptococci (GAS) infections, including necrotizing fasciitis and myonecrosis, are life-threatening and reemerging globally.
  • A significant proportion of GAS myonecrosis cases lack a clear entry point, with infections often establishing at sites of prior minor trauma.

Purpose of the Study:

  • To investigate the molecular mechanisms by which GAS establishes infection at sites of minor muscle injury.
  • To identify specific skeletal muscle cell surface molecules that GAS binds to during infection.

Main Methods:

  • Isolation and identification of GAS-binding proteins from skeletal muscle cells.
  • In vitro assessment of vimentin expression on injured skeletal muscle cells.
  • Analysis of vimentin expression in muscle tissue from a patient with fatal GAS myonecrosis.

Main Results:

  • Vimentin was identified as the primary protein on skeletal muscle cells to which GAS binds.
  • Vimentin expression was significantly increased on injured skeletal muscle cells in vitro.
  • Vimentin was present in muscle tissue from a patient who succumbed to GAS myonecrosis and streptococcal toxic shock syndrome.

Conclusions:

  • GAS utilizes vimentin, upregulated on injured muscle, as a key binding protein to initiate infection.
  • This molecular interaction provides a mechanism explaining GAS soft-tissue infections at sites of prior minor muscle trauma.
  • Understanding this pathway may lead to novel preventive strategies and treatments for severe GAS infections.

Related Concept Videos

Streptococcal Pharyngitis01:27

Streptococcal Pharyngitis

Streptococcal pharyngitis, commonly known as “strep throat,” is an acute infection of the oropharyngeal tissues caused by the Gram‑positive Group A Streptococcus (Streptococcus pyogenes). Transmission occurs primarily through respiratory droplets expelled during coughing, sneezing, or talking.Mechanisms of Host Entry and Immune EvasionUpon entering the host, S. pyogenes adheres to the mucosal epithelial cells of the pharynx via surface proteins, notably lipoteichoic acid and the antiphagocytic...
Determinants of Bacterial Pathogenicity and Virulence01:20

Determinants of Bacterial Pathogenicity and Virulence

Pathogenic bacteria employ a variety of strategies to establish infections, including the secretion of extracellular enzymes that act as potent virulence factors. These enzymes facilitate bacterial colonization of host tissues and help evade immune surveillance. By targeting structural components of host tissues and interfering with immune mechanisms, these enzymes play a pivotal role in disease progression.Extracellular Enzymes Facilitating Tissue Invasion: Several bacterial pathogens secrete...
Myocarditis I: Introduction01:21

Myocarditis I: Introduction

Myocarditis is inflammation of the myocardium, which is the muscular layer of the heart.EtiologyMyocarditis has a diverse etiology, including a wide range of infectious and non-infectious causes:Infectious CausesViral: Common viruses include Coxsackie A and B, adenovirus, parvovirus B19, enteroviruses, and influenza A.Bacterial: Examples include infections caused by Streptococcus, Staphylococcus, and Mycoplasma species.Rickettsial: Infections like Rocky Mountain spotted fever can result in...
Disorders of the Skeletal Muscle01:28

Disorders of the Skeletal Muscle

The clinical conditions affecting the skeletal muscle tissue are broadly categorized as musculoskeletal and neuromuscular disorders.
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...
Formation of Muscle Fibers from Myoblasts01:13

Formation of Muscle Fibers from Myoblasts

De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
Tissue Injury: Inflammation and Repair01:28

Tissue Injury: Inflammation and Repair

Following injury, the integrity of the injured tissues must be reestablished. For example, in skin tissue, wound repair involves coordination among resident skin cells, blood mononuclear cells, extracellular matrix, growth factors, and cytokines to complete the healing cascade.
Formation of Blood Clot
In case of deep injuries, trauma to blood vessels results in blood loss. In the meantime, phospholipids released from the ruptured endothelial cellular membrane are converted into arachidonic...