Open AccessThe pathogenic Escherichia coli type III secreted protease NleC degrades the host acetyltransferase p300
Author(s) -
Shames Stephanie R.,
Bhavsar Amit P.,
Croxen Matthew A.,
Law Robyn J.,
Mak Stefanie H. C.,
Deng Wanyin,
Li Yuling,
Bidshari Roza,
de Hoog Carmen L.,
Foster Leonard J.,
Finlay B. Brett
Publication year - 2011
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2011.01640.x
Subject(s) - biology , secretion , virulence , effector , microbiology and biotechnology , metalloproteinase , enteropathogenic escherichia coli , escherichia coli , type three secretion system , protease , virulence factor , gene , matrix metalloproteinase , enzyme , genetics , biochemistry
Summary 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 Δ nleC ‐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.