SOS regulatory elements are essential for UPEC pathogenesis.
Epithelial cells are highly regarded as the first line of defense against microorganisms, but the mechanisms used to control bacterial diseases are poorly understood. A component of the DNA damage repair regulon, SulA, is essential for UPEC virulence in a mouse model for human urinary tract infection, suggesting that DNA damage is a key mediator in the primary control of pathogens within the epithelium. In this study, we examine the role of DNA damage repair regulators in the intracellular lifestyle of UPEC within superficial bladder epithelial cells. LexA and RecA coordinate various operons for repair of DNA damage due to exogenous and endogenous agents and are known regulators of sulA. UPEC strains defective in regulation of the SOS response mediated by RecA and LexA display attenuated virulence in immunocompetent mice within the first 6 h post infection. RecA and LexA regulation of the SOS regulon is dispensable in immunocompromised mice. These data suggest that epithelial cells produce sufficient levels of DNA damaging agents, such that the bacterial DNA damage repair response is essential, as a means to control invading bacteria. Since many pathogens interact with the epithelium before exposure to professional phagocytes, it is likely that adaptation to oxidative radicals during intracellular growth provides additional protection from killing by innate immune phagocytes.
Li
Birong
B
Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, The Ohio State University School of Medicine, Columbus, OH 43205, USA.
Smith
Peter
P
Horvath
Dennis J
DJ
Romesberg
Floyd E
FE
Justice
Sheryl S
SS
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology*; D029968:Escherichia coli Proteins / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism*; D013014:SOS Response, Genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001743:Urinary Bladder / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000472:pathogenicity*; D014774:Virulence; D000099160:LexA Repressor Protein
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D011938:Rec A Recombinases; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein; C053139:sulA protein, E coli