Molecular Aspects of Host-pathogen Interactions in the Urinary Tract PDF Download

Author: Matthew J. Duncan
Publisher:
ISBN: 9781109909654
Category : Urinary tract infections
Languages : en
Pages : 147

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Book Description
Urinary tract infections are one of the most common bacterial infections in humans and diagnosis and treatment of UTIs among women in the United States alone is the cause for an estimated 8 million office visits per year, and up to 25% of women who experience a first UTI will have a second infection within 6 months. Type 1 fimbriated Escherichia coli represents the most common uropathogen, owing much of its virulence to adherence and invasion of the uroepithelium, mediated by bacterial type 1 fimbriae. Type 1 fimbriae are heteropolymeric organelles of adhesion composed of the tip-located adhesin FimH and a fimbrial shaft. Previously, the specificity of uropathogenic E. coli type 1 fimbriae for the uroepithelium was thought to be mediated by the amino acid structure of FimH, but in these studies, we have demonstrated that the fimbrial shaft also plays a role in determining E. coli type 1 fimbriae-mediated tissue tropism. As well as mediating adherence, E. coli type 1 fimbriae also mediate invasion of the uroepithelium, which could explain the frequent recurrence of E. coli infections of the bladder and their apparent resistance to antibiotic therapy. Using in vitro systems, as well as a mouse model of urinary tract infection, we demonstrated that host cell lipid rafts, which are cholesterol and sphingolipid enriched membrane domains, were required for E. coli uroepithelial invasion. Through this, and the development of an additional model of a lipid raft targeting bacterium, we found that targeting lipid rafts allows bacteria to bypass the barrier function of the mucosal epithelium, and to invade immune cells via a route that avoids the immune cell's bactericidal functions. In summary, we have demonstrated a novel modulator of type 1 fimbrial specificity which allows E. coli to target uroepithelial lipid rafts for invasion. As more and more bacterial pathogens are found to target host cell lipid rafts, the importance of studying bacterial-host cell lipid raft interactions becomes clearer. Understanding the mechanics of these interactions, and the bacterial advantage gained by targeting lipid rafts, could lead to novel therapeutic regimes to treat infections caused by lipid raft targeting pathogens.