Invasive and adherent bacterial pathogens co-Opt host clathrin for infection.
Infection by the bacterium Listeria monocytogenes depends on host cell clathrin. To determine whether this requirement is widespread, we analyzed infection models using diverse bacteria. We demonstrated that bacteria that enter cells following binding to cellular receptors (termed "zippering" bacteria) invade in a clathrin-dependent manner. In contrast, bacteria that inject effector proteins into host cells in order to gain entry (termed "triggering" bacteria) invade in a clathrin-independent manner. Strikingly, enteropathogenic Escherichia coli (EPEC) required clathrin to form actin-rich pedestals in host cells beneath adhering bacteria, even though this pathogen remains extracellular. Furthermore, clathrin accumulation preceded the actin rearrangements necessary for Listeria entry. These data provide evidence for a clathrin-based entry pathway allowing internalization of large objects (bacteria and ligand-coated beads) and used by "zippering" bacteria as part of a general mechanism to invade host mammalian cells. We also revealed a nonendocytic role for clathrin required for extracellular EPEC infections.
Veiga
Esteban
E
Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris F-75015, France. eveiga@pasteur.fr
Guttman
Julian A
JA
Bonazzi
Matteo
M
Boucrot
Emmanuel
E
Toledo-Arana
Alejandro
A
Lin
Ann E
AE
Enninga
Jost
J
Pizarro-Cerdá
Javier
J
Finlay
B Brett
BB
Kirchhausen
Tomas
T
Cossart
Pascale
P
D000199:Actins / Q000378:metabolism; D000818:Animals; D001419:Bacteria / Q000378:metabolism / Q000472:pathogenicity*; D001422:Bacterial Adhesion / Q000502:physiology*; D002460:Cell Line; D002966:Clathrin / Q000502:physiology*; D034281:Dynamins / Q000502:physiology; D004705:Endocytosis / Q000502:physiology*; D054308:Enteropathogenic Escherichia coli / Q000472:pathogenicity / Q000502:physiology; D004927:Escherichia coli Infections / Q000382:microbiology; D006801:Humans; D008089:Listeria monocytogenes / Q000472:pathogenicity / Q000502:physiology; D008088:Listeriosis / Q000382:microbiology; D011956:Receptors, Cell Surface / Q000378:metabolism; D014774:Virulence
D000199:Actins; D002966:Clathrin; D011956:Receptors, Cell Surface; D034281:Dynamins