title: The F pilus mediates a novel pathway of CDI toxin import.
abstract: Contact-dependent growth inhibition (CDI) is a widespread form of inter-bacterial competition that requires direct cell-to-cell contact. CDI(+) inhibitor cells express CdiA effector proteins on their surface. CdiA binds to specific receptors on susceptible target bacteria and delivers a toxin derived from its C-terminal region (CdiA-CT). Here, we show that purified CdiA-CT(536) toxin from uropathogenic Escherichia coli 536 translocates into bacteria, thereby by-passing the requirement for cell-to-cell contact during toxin delivery. Genetic analyses demonstrate that the N-terminal domain of CdiA-CT(536) is necessary and sufficient for toxin import. The CdiA receptor plays no role in this import pathway; nor do the Tol and Ton systems, which are exploited to internalize colicin toxins. Instead, CdiA-CT(536) import requires conjugative F pili. We provide evidence that the N-terminal domain of CdiA-CT(536) interacts with F pilin, and that pilus retraction is critical for toxin import. This pathway is reminiscent of the strategy used by small RNA leviviruses to infect F(+) cells. We propose that CdiA-CT(536) mimics the pilin-binding maturation proteins of leviviruses, allowing the toxin to bind F pili and become internalized during pilus retraction.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, 93106-9625, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Beck
authors.forename: Elie J
authors.initials: EJ
authors.lastname: Diner
authors.forename: Jeff J
authors.initials: JJ
authors.lastname: Kim
authors.forename: David A
authors.initials: DA
authors.lastname: Low
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hayes
mesh_terms: D000595:Amino Acid Sequence; D000898:Antibiosis / Q000502:physiology*; D001427:Bacterial Toxins / Q000302:isolation & purification* / Q000378:metabolism; D017104:Bacteriophage M13 / Q000502:physiology; D001435:Bacteriophages / Q000502:physiology; D003227:Conjugation, Genetic; D003260:Contact Inhibition; D004722:Endoribonucleases / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000302:isolation & purification / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000378:metabolism / Q000502:physiology*; D017909:Levivirus / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport
chemical_list: D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D004722:Endoribonucleases; C515828:colicin E5 protein, E coli