Aberrant Community Architecture and Attenuated Persistence of Uropathogenic Escherichia coli in the Absence of Individual IHF Subunits

被引:22
作者
Justice, Sheryl S. [1 ,2 ]
Li, Birong [1 ]
Downey, Jennifer S. [3 ]
Dabdoub, Shareef M. [1 ]
Brockson, M. Elizabeth [1 ]
Probst, G. Duane [1 ]
Ray, William C. [4 ]
Goodman, Steven D. [3 ]
机构
[1] Nationwide Childrens Hosp, Res Inst, Ctr Microbial Pathogenesis, Columbus, OH USA
[2] Ohio State Univ, Coll Med, Dept Pediat & Urol, Columbus, OH 43210 USA
[3] Univ So Calif, Herman Ostrow Sch Dent, Div Biomed Sci, Los Angeles, CA USA
[4] Nationwide Childrens Hosp, Res Inst, Battelle Ctr Math Med, Columbus, OH USA
来源
PLOS ONE | 2012年 / 7卷 / 10期
基金
美国国家卫生研究院;
关键词
INTEGRATION HOST FACTOR; INTRACELLULAR BACTERIAL COMMUNITIES; SITE-SPECIFIC RECOMBINATION; URINARY-TRACT-INFECTION; DNA-BINDING PROTEIN; TYPE-1; FIMBRIAE; PHASE VARIATION; HIMA GENE; EXPRESSION; SURA;
D O I
10.1371/journal.pone.0048349
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:11
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