Cytolysin-mediated translocation (CMT): a functional equivalent of type III secretion in gram-positive bacteria.
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.
Madden
J C
JC
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ruiz
N
N
Caparon
M
M
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism; D001422:Bacterial Adhesion / Q000502:physiology; D001426:Bacterial Proteins; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D036563:Cyclic ADP-Ribose; D003593:Cytoplasm / Q000201:enzymology; D003603:Cytotoxins / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000382:microbiology; D009244:NAD+ Nucleosidase / Q000378:metabolism; D021382:Protein Sorting Signals / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D013297:Streptococcus pyogenes / Q000378:metabolism* / Q000472:pathogenicity; D013301:Streptolysins / Q000378:metabolism*; D014774:Virulence
D001426:Bacterial Proteins; D003603:Cytotoxins; D021382:Protein Sorting Signals; D013301:Streptolysins; C025964:streptolysin O; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D009244:NAD+ Nucleosidase