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Cytolysin-mediated translocation (CMT): a functional equivalent of type III secretion in gram-positive bacteria

J C Madden1, N Ruiz, M Caparon

  • 1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Cell
|February 13, 2001
PubMed

Insights

Gram-positive bacteria like Streptococcus pyogenes use a novel pathway involving streptolysin O (SLO) to inject effector proteins. This cytolysin-mediated translocation (CMT) mechanism is key for pathogen virulence.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Type III secretion systems are crucial for Gram-positive bacterial virulence but their mechanisms remain poorly understood.
  • Streptococcus pyogenes is a significant Gram-positive pathogen responsible for various human diseases.

Purpose of the Study:

  • To elucidate the mechanism of effector protein injection by the Gram-positive pathogen Streptococcus pyogenes.
  • To investigate the role of streptolysin O (SLO) in mediating protein translocation into host cells.
  • To establish a novel paradigm for Gram-positive bacterial secretion.

Main Methods:

  • Investigated the interaction between SLO and effector proteins.
  • Utilized cell-based assays to demonstrate protein translocation.
  • Analyzed the synergistic cytotoxicity of SLO and the effector SPN.

Main Results:

  • Described a novel injection pathway for Gram-positive bacteria utilizing SLO, a cholesterol-dependent cytolysin.
  • Demonstrated that the effector SPN (S. pyogenes NAD-glycohydrolase) is translocated through the SLO pore via a polarized process.
  • Showed that SLO and SPN act synergistically to induce cytotoxicity, with SPN producing cyclic ADP-ribose.

Conclusions:

  • Cytolysin-mediated translocation (CMT) represents a novel mechanism for effector delivery by Gram-positive pathogens.
  • SLO-mediated translocation provides a functional equivalent to Type III secretion for Gram-positive bacteria.
  • This discovery offers new insights into the function of cholesterol-dependent cytolysins and their role in bacterial pathogenesis.

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