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Host DNA repair proteins in response to Pseudomonas aeruginosa in lung epitehlial cells and in mice

Permanent URL:
http://handle.nal.usda.gov/10113/58091
Abstract:
Host DNA damage and DNA repair response to bacterial infections and its significance are not fully understood. Here, we demonstrate that infection by Gram-negative bacterium P. aeruginosa significantly altered the expression and enzymatic activity of base excision DNA repair protein OGG1 in lung epithelial cells. Down-regulation of OGG1 with siRNA strategy resulted in severe DNA damage and cell death. In addition, OGG1 knockout mice infected by P. aeruginosa exhibited increased lung injury with higher activities of myeloperoxidase and lipid peroxidation. Furthermore, acetylation of OGG1 correlates with host responses to bacterial genotoxicity as mutations of OGG1 acetylation sites increased nuclear excision DNA repair protein CSB expression. An interaction between OGG1 and CSB was identified during infection, indicating that a synergy between these two DNA repair pathways is required for the repair of damaged DNA. This synergy may be critical for maintaining homeostasis in severe infection cases. ExoS, a major virulence factor belonging to type 3 secretion system exoenzymes, was found to induce activities of DNA repair protein OGG1 and ERK1/2, whereas siRNA inhibition of ERK1/2 decreased cell proliferation in an Akt dependent manner. Together, our studies indicate that DNA damage responses by certain DNA repair proteins, along with other signaling systems (e.g., Akt), play a concerted role in host defense against P. aeruginosa, and may be promising targets for the treatment of Gram-negative bacterial infection.
Author(s):
MIN WU , HUANG HUANG , WEIDONG ZHANG , SHIBICHAKRAVART KANNAN , ANDREW WEAVER , MOLYNDA MCKIBBEN , DANIELLE HERINGTON , HUAWEI ZENG , HONGWEI GAO
Subject(s):
DNA damage , DNA repair , Gram-negative bacteria , Pseudomonas aeruginosa , acetylation , bacterial infections , cell death , cell proliferation , enzyme activity , epithelial cells , gene expression regulation , genotoxicity , lipid peroxidation , lungs , mice , mutation , myeloperoxidase , proteins , secretion , small interfering RNA , virulence
Source:
Infection and Immunity 2011 1 v.79 no.1
Language:
English
Year:
2011
Collection:
Journal Articles, USDA Authors, Peer-Reviewed
File:
Download [PDF File]
Rights:
Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.