Resistance to phagocytosis by Yersinia.
Enteropathogenic species of the genus Yersinia penetrate the intestinal epithelium and then spread to the lymphatic system, where they proliferate extracellularly. At this location, most other bacteria are effectively ingested and destroyed by the resident phagocytes. Yersinia, on the other hand binds to receptors on the external surface of phagocytes, and from this location it blocks the capacity of these cells to exert their phagocytic function via different receptors. The mechanism behind the resistance to phagocytosis involves the essential virulence factor YopH, a protein tyrosine phosphatase that is translocated into interacting target cells via a type III secretion machinery. YopH disrupts peripheral focal complexes of host cells, seen as a rounding up of infected cells. The focal complex proteins that are dephosphorylated by YopH are focal adhesion kinase and Crk-associated substrate, the latter of which is a common substrate in both professional and non-professional phagocytes. In macrophages additional substrates have been found, the Fyn-binding/SLP-76-associated protein and SKAP-HOM. Phagocytosis is a rapid process that is activated when the bacterium interacts with the phagocyte. Consequently, the effect exerted by a microbe to block this process has to be rapid and precise. This review deals with the mechanisms involved in impeding uptake as well as with the role of the YopH substrates and focal complex structures in normal cell function.
Fällman
Maria
M
Department of Molecular Biology, Umeå University, Sweden. Maria.Fällman@cmb.umu.se
Deleuil
Fabienne
F
McGee
Karen
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D010587:Phagocytosis; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014774:Virulence; D015007:Yersinia / Q000378:metabolism / Q000472:pathogenicity*; D015009:Yersinia Infections / Q000382:microbiology
D048868:Adaptor Proteins, Signal Transducing; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C106957:FYB1 protein, human; D008565:Membrane Proteins; C109742:SLMAP protein, human; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia