Cytolysin-mediated Translocation (CMT): A Functional Equivalent of Type III Secretion in Gram-Positive Bacteria

Cell. 2001 Jan 12;104(1):143-52. doi: 10.1016/s0092-8674(01)00198-2.


Type III secretion for injection of effector proteins into host cells has not been described for Gram-positive bacteria despite their importance in disease. Here, we describe an injection pathway for the Gram-positive pathogen Streptococcus pyogenes that utilizes streptolysin O (SLO), a cholesterol-dependent cytolysin. The data support a model in which an effector is translocated through the SLO pore by a polarized process. The effector, SPN (S. pyogenes NAD-glycohydrolase), is capable of producing the potent second messenger cyclic ADP-ribose, and SLO and SPN act synergistically to trigger cytotoxicity. These data provide a novel paradigm for the function of the cholesterol-dependent cytolysin family and its wide distribution suggests that cytolysin-mediated translocation (CMT) may be the equivalent of type III secretion for Gram-positive pathogens.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate Ribose / analogs & derivatives*
  • Adenosine Diphosphate Ribose / metabolism
  • Bacterial Adhesion / physiology
  • Bacterial Proteins
  • Biological Transport / physiology
  • Cell Line
  • Cell Membrane / metabolism
  • Cyclic ADP-Ribose
  • Cytoplasm / enzymology
  • Cytotoxins / metabolism*
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / microbiology
  • NAD+ Nucleosidase / metabolism
  • Protein Sorting Signals / physiology
  • Second Messenger Systems / physiology
  • Streptococcus pyogenes / metabolism*
  • Streptococcus pyogenes / pathogenicity
  • Streptolysins / metabolism*
  • Virulence


  • Bacterial Proteins
  • Cytotoxins
  • Protein Sorting Signals
  • Streptolysins
  • streptolysin O
  • Cyclic ADP-Ribose
  • Adenosine Diphosphate Ribose
  • NAD+ Nucleosidase