Streptococcal pyrogenic exotoxin B cleaves properdin and inhibits complement-mediated opsonophagocytosis

Nina Tsao1, Wan-Hua Tsai, Yee-Shin Lin

  • 1Department of Biological Science and Technology, I-Shou University, Kaohsiung County, Taiwan.

Insights

Group A Streptococcus uses pyrogenic exotoxin B (SPE B) to degrade serum properdin, a novel mechanism that helps bacteria evade immune cells and resist phagocytosis during infection.

Area of Science:

  • Microbiology
  • Immunology
  • Biochemistry

Background:

  • Streptococcal pyrogenic exotoxin B (SPE B) is a key virulence factor in Group A Streptococcus (GAS) infections.
  • SPE B's ability to reduce phagocytic activity suggests a role in bacterial evasion of host immune defenses.

Purpose of the Study:

  • To elucidate the mechanism by which SPE B facilitates bacterial resistance to opsonophagocytosis.
  • To investigate the interaction of SPE B with serum components involved in complement-mediated immunity.

Main Methods:

  • Western blotting was employed to detect interactions between SPE B and serum proteins.
  • Affinity chromatography using immobilized SPE B identified properdin as a binding partner.
  • Functional assays assessed the impact of SPE B on the alternative complement pathway and neutrophil killing.

Main Results:

  • Both active SPE B and its protease-inactive mutant (C192S) bound to serum properdin.
  • Active SPE B, but not C192S, degraded properdin, leading to the blockage of the alternative complement pathway.
  • Properdin reconstitution restored alternative pathway function in SPE B-treated serum.
  • GAS opsonized with SPE B-treated serum exhibited increased resistance to neutrophil-mediated killing.

Conclusions:

  • Group A Streptococcus employs a novel mechanism involving the degradation of serum properdin by SPE B to evade opsonophagocytosis.
  • This degradation of properdin by SPE B impairs the alternative complement pathway, contributing to bacterial survival.

Related Concept Videos

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...
Complement System01:27

Complement System

The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a membrane...
Diphtheria01:28

Diphtheria

Diphtheria is an acute, toxin-mediated infectious disease that primarily affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, a Gram-positive, pleomorphic rod that lacks spore-forming capability and exhibits a characteristic club-shaped morphology under microscopic examination. While C. diphtheriae can asymptomatically colonize mucosal surfaces, clinical disease manifests only when the bacterial strain is lysogenized by a specific β-corynephage. This phage...
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...
Bacterial Toxins01:12

Bacterial Toxins

Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
Antibody Actions01:26

Antibody Actions

Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...