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Linkage of T3 and Cpa pilins in the Streptococcus pyogenes M3 pilus

Bernard R Quigley1, Dorothea Zähner, Matthew Hatkoff

  • 1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Molecular Microbiology
|May 13, 2009
PubMed

Insights

Streptococcus pyogenes pili are crucial for infection. Researchers identified key residues and mechanisms for pilus assembly, revealing the adhesin Cpa is located at the pilus tip, offering a new anti-infective target.

Area of Science:

  • Microbiology
  • Structural Biology
  • Infectious Diseases

Background:

  • * Streptococcus pyogenes (group A streptococcus, GAS) uses pili for host tissue attachment, making pili a target for anti-infective strategies.
  • * The T3 pilus of GAS is composed of T3 protein subunits with minor pilins Cpa and OrfB, lacking typical polymerization motifs found in other Gram-positive bacteria.

Purpose of the Study:

  • * To investigate the specific residues and mechanisms involved in the covalent linkage of GAS pilins.
  • * To elucidate the role of the sortase SrtC2 and specific motifs in T3 pilus assembly and adhesin attachment.

Main Methods:

  • * Investigated the role of the VPPTG motif in Cpa's cell wall-sorting signal for SrtC2-mediated linkage.
  • * Analyzed the function of K173 residue in T3 protein for both pilus polymerization and Cpa attachment.
  • * Employed immunogold electron microscopy to determine the location of Cpa on the pilus structure.

Main Results:

  • * SrtC2-mediated linkage of Cpa to T3 requires the VPPTG motif in Cpa.
  • * Residue K173 of T3 is essential for both T3 polymerization and Cpa attachment to the pilus.
  • * Cpa attachment to K173 of T3 blocks further T3 subunit addition, indicating Cpa is exclusively at the pilus tip.

Conclusions:

  • * The study reveals the mechanism of T3 pilus assembly in GAS, highlighting the importance of specific residues and motifs.
  • * Cpa's exclusive location at the pilus tip suggests its role in presenting adhesins externally, similar to Gram-negative bacterial pili.
  • * Understanding these mechanisms provides a basis for developing novel anti-infective strategies targeting GAS pilus assembly.

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