Anaplasma phagocytophilum AptA modulates Erk1/2 signalling.
Anaplasma phagocytophilum causes human granulocytic anaplasmosis, one of the most common tick-borne diseases in North America. This unusual obligate intracellular pathogen selectively persists within polymorphonuclear leucocytes. In this study, using the yeast surrogate model we identified an A. phagocytophilum virulence protein, AptA (A. phagocytophilum toxin A), that activates mammalian Erk1/2 mitogen-activated protein kinase. This activation is important for A. phagocytophilum survival within human neutrophils. AptA interacts with the intermediate filament protein vimentin, which is essential for A. phagocytophilum-induced Erk1/2 activation and infection. A. phagocytophilum infection reorganizes vimentin around the bacterial inclusion, thereby contributing to intracellular survival. These observations reveal a major role for the bacterial protein, AptA, and the host protein, vimentin, in the activation of Erk1/2 during A. phagocytophilum infection.
Sukumaran
Bindu
B
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8022, USA.
Mastronunzio
Juliana E
JE
Narasimhan
Sukanya
S
Fankhauser
Sarah
S
Uchil
Pradeep D
PD
Levy
Roie
R
Graham
Morven
M
Colpitts
Tonya Michelle
TM
Lesser
Cammie F
CF
Fikrig
Erol
E
D041081:Anaplasma phagocytophilum / Q000472:pathogenicity*; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009504:Neutrophils / Q000382:microbiology; D015398:Signal Transduction; D014746:Vimentin / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism*
D001426:Bacterial Proteins; D014746:Vimentin; D037521:Virulence Factors; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3