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Streptococcal Lancefield polysaccharides are critical cell wall determinants for human Group IIA secreted

Vincent P van Hensbergen1, Elin Movert2, Vincent de Maat1

  • 1Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Plos Pathogens
|October 16, 2018
PubMed

Insights

Human Group IIA secreted phospholipase A2 (hGIIA) kills bacteria, but Group A Streptococcus (GAS) is resistant. Researchers found that altering the Group A Carbohydrate (GAC) structure significantly increases resistance to hGIIA, revealing a key bacterial defense mechanism.

Area of Science:

  • Microbiology
  • Immunology
  • Biochemistry

Background:

  • Human Group IIA secreted phospholipase A2 (hGIIA) is an innate immune protein with bactericidal activity against Gram-positive bacteria.
  • hGIIA plays a role in defense against pathogens like Group A Streptococcus (GAS) and Group B Streptococcus (GBS).
  • GAS exhibits remarkable resistance to hGIIA compared to other Gram-positive bacteria, necessitating investigation into its resistance mechanisms.

Purpose of the Study:

  • To identify genetic mechanisms underlying GAS resistance to hGIIA.
  • To elucidate the role of the Group A Carbohydrate (GAC) in hGIIA resistance.
  • To understand how streptococcal Lancefield antigens influence hGIIA's bactericidal function.

Main Methods:

  • Utilized transposon sequencing (Tn-seq) on a saturated GAS M1 transposon library exposed to hGIIA.
  • Analyzed mutant abundance to identify genes conferring hGIIA susceptibility or resistance.
  • Generated and characterized GAS isogenic mutants (ΔgacI) and complemented strains to assess the role of GAC in hGIIA resistance.

Main Results:

  • Identified nine genes, including dltA and lytR, that increase hGIIA susceptibility in GAS.
  • Discovered seven genes conferring hGIIA resistance, including gacH and gacI within the GAC gene cluster.
  • Demonstrated that loss of the GAC N-acetylglucosamine side chain in ΔgacI mutants increases hGIIA resistance approximately 10-fold.
  • Observed that loss of the Lancefield Group B Carbohydrate (GBC) in GBS also increased resistance to hGIIA-mediated killing.

Conclusions:

  • GAS resistance to hGIIA involves multiple genetic factors, including those affecting the GAC structure.
  • The GAC and GBC, critical streptococcal antigens, are required for hGIIA's bactericidal activity.
  • These findings highlight the importance of streptococcal cell wall carbohydrates in evading innate immune defenses like hGIIA.

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