Role for FimH in Extraintestinal Pathogenic Escherichia coli Invasion and Translocation through the Intestinal Epithelium

被引:34
|
作者
Poole, Nina M. [1 ]
Green, Sabrina I. [1 ]
Rajan, Anubama [1 ]
Vela, Luz E. [1 ]
Zeng, Xi-Lei [1 ]
Estes, Mary K. [1 ]
Maresso, Anthony W. [1 ]
机构
[1] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA
关键词
ExPEC; FimH; intestinal epithelium; invasion; translocation; URINARY-TRACT-INFECTION; LACTAMASE-PRODUCING ENTEROBACTERIACEAE; BLOOD-STREAM INFECTIONS; BACTERIAL TRANSLOCATION; GASTROINTESTINAL-TRACT; INDIGENOUS BACTERIA; SIDEROPHORE RECEPTOR; STRUCTURAL BASIS; TYPE-1; FIMBRIAE; PHASE VARIATION;
D O I
10.1128/IAI.00581-17
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The translocation of bacteria across the intestinal epithelium of 'immunocompromised patients can lead to bacteremia and life-threatening sepsis. Extraintestinal pathogenic Escherichia coli (ExPEC), so named because this pathotype infects tissues distal to the intestinal tract, is a frequent cause of such infections, is often multidrug resistant, and chronically colonizes a sizable portion of the healthy population. Although several virulence factors and their roles in pathogenesis are well described for ExPEC strains that cause urinary tract infections and meningitis, they have not been linked to translocation through intestinal barriers, a fundamentally distant yet important clinical phenomenon. Using untransformed ex situ human intestinal enteroids and transformed Caco-2 cells, we report that ExPEC strain CP9 binds to and invades the intestinal epithelium. ExPEC harboring a deletion of the gene encoding the mannose-binding type 1 pilus tip protein FimH demonstrated reduced binding and invasion compared to strains lacking known E. coli virulence factors. Furthermore, in a murine model of chemotherapy-induced translocation, ExPEC lacking fimH colonized at levels comparable to that of the wild type but demonstrated a statistically significant reduction in translocation to the kidneys, spleen, and lungs. Collectively, this study indicates that FimH is important for ExPEC translocation, suggesting that the type 1 pilus is a therapeutic target for the prevention of this process. Our study also highlights the use of human intestinal enteroids in the study of enteric diseases.
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页数:14
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