title: The pathogenic Escherichia coli type III secreted protease NleC degrades the host acetyltransferase p300.
abstract: Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC respectively) are attaching and effacing bacterial pathogens that cause devastating diarrhoeal disease worldwide. These pathogens depend on a type III secretion system, which functions as a molecular syringe to translocate bacterial effector proteins directly into infected host cells. One of these effectors, NleC, was recently described as a zinc metalloprotease that targets NF-κB Rel-A (p65) and thus contributes to dampening of inflammatory signalling during EPEC and EHEC infection. We have identified the acetyltransferase p300 as an additional target of NleC. Several biochemical techniques were employed to demonstrate specific binding of p300 by NleC. We also show that NleC causes decreased abundance of p300 in cellular nuclei and that the metalloprotease domain of NleC is responsible for this phenotype. Furthermore, we demonstrate that overexpression of p300 can antagonize repression of IL-8 secretion by EPEC and that siRNA knock-down of p300 dampens IL-8 secretion by EPEC ΔnleC-infected cells. We have therefore identified a second target of NleC and provided the first example of a bacterial virulence factor targeting the acetyltransferase p300.
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, V6T 1Z4, Canada.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Shames
authors.forename: Amit P
authors.initials: AP
authors.lastname: Bhavsar
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Croxen
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Law
authors.forename: Stefanie H C
authors.initials: SH
authors.lastname: Mak
authors.forename: Wanyin
authors.initials: W
authors.lastname: Deng
authors.forename: Yuling
authors.initials: Y
authors.lastname: Li
authors.forename: Roza
authors.initials: R
authors.lastname: Bidshari
authors.forename: Carmen L
authors.initials: CL
authors.lastname: de Hoog
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D002460:Cell Line; D004926:Escherichia coli / Q000201:enzymology* / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D059748:Proteolysis; D037521:Virulence Factors / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D029968:Escherichia coli Proteins; D037521:Virulence Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C506688:Z0986 protein, E coli