Human-restricted bacterial pathogens block shedding of epithelial cells by stimulating integrin activation.
Colonization of mucosal surfaces is the key initial step in most bacterial infections. One mechanism protecting the mucosa is the rapid shedding of epithelial cells, also termed exfoliation, but it is unclear how pathogens counteract this process. We found that carcinoembryonic antigen (CEA)-binding bacteria colonized the urogenital tract of CEA transgenic mice, but not of wild-type mice, by suppressing exfoliation of mucosal cells. CEA binding triggered de novo expression of the transforming growth factor receptor CD105, changing focal adhesion composition and activating beta1 integrins. This manipulation of integrin inside-out signaling promotes efficient mucosal colonization and represents a potential target to prevent or cure bacterial infections.
Muenzner
Petra
P
Lehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, 78457 Konstanz, Germany.
Bachmann
Verena
V
Zimmermann
Wolfgang
W
Hentschel
Jochen
J
Hauck
Christof R
CR
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D000071063:Endoglin; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology*; D005260:Female; D022001:Focal Adhesions; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000378:metabolism; D006069:Gonorrhea / Q000382:microbiology*; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000382:microbiology; D009344:Neisseria gonorrhoeae / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014621:Vagina / Q000166:cytology / Q000382:microbiology* / Q000473:pathology; D060589:Zyxin
D000942:Antigens, Bacterial; D015703:Antigens, CD; C527875:CEACAM5 protein, human; D002272:Carcinoembryonic Antigen; D003598:Cytoskeletal Proteins; C064206:ENG protein, human; D000071063:Endoglin; C502004:Eng protein, mouse; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D039641:Integrin beta Chains; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C092842:ZYX protein, human; D060589:Zyxin; C050308:opacity proteins