Aberrant community architecture and attenuated persistence of uropathogenic Escherichia coli in the absence of individual IHF subunits

• Published in: PloS one 2012-10, Vol.7 (10), p.e48349-e48349
• Main Authors: Justice, Sheryl S, Li, Birong, Downey, Jennifer S, Dabdoub, Shareef M, Brockson, M Elizabeth, Probst, G Duane, Ray, William C, Goodman, Steven D
• Format: Article
• Language: English
• Subjects: Aberration; Animal models; Animals; Architecture; Bacteria; Binding sites; Biology; Bladder; Cell division; Children & youth; Cholera; Chromosomes; Colonization; Communities; Cystitis; Cytoplasm; Dentistry; Deoxyribonuclease I - metabolism; Deoxyribonucleic acid; Dimerization; DNA; DNA, Bacterial - metabolism; E coli; Environmental DNA; Epithelial cells; Escherichia coli; Escherichia coli Infections - microbiology; Families & family life; Female; Gene expression; Hospitals; Humans; Integration host factor; Integration Host Factors - genetics; Kidney - microbiology; Kidneys; Laboratories; Medicine; Mice; Mice, Inbred C3H; Microscopy, Fluorescence - methods; Models, Genetic; Molecular biology; Mutation; Pathogenesis; Pili; Promoter Regions, Genetic; Protein binding; Restoration; Urinary bladder; Urinary Bladder - microbiology; Urinary tract; Urinary tract diseases; Urinary tract infections; Urinary Tract Infections - microbiology; Urogenital system; Uropathogenic Escherichia coli - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0048349

Uropathogenic Escherichia coli (UPEC) utilizes a complex community-based developmental pathway for growth within superficial epithelial cells of the bladder during cystitis. Extracellular DNA (eDNA) is a common matrix component of organized bacterial communities. Integration host factor (IHF) is a heterodimeric protein that binds to double-stranded DNA and produces a hairpin bend. IHF-dependent DNA architectural changes act both intrabacterially and extrabacterially to regulate gene expression and community stability, respectively. We demonstrate that both IHF subunits are required for efficient colonization of the bladder, but are dispensable for early colonization of the kidney. The community architecture of the intracellular bacterial communities (IBCs) is quantitatively different in the absence of either IhfA or IhfB in the murine model for human urinary tract infection (UTI). Restoration of Type 1 pili by ectopic production does not restore colonization in the absence of IhfA, but partially compensates in the absence of IhfB. Furthermore, we describe a binding site for IHF that is upstream of the operon that encodes for the P-pilus. Taken together, these data suggest that both IHF and its constituent subunits (independent of the heterodimer), are able to participate in multiple aspects of the UPEC pathogenic lifestyle, and may have utility as a target for treatment of bacterial cystitis.