(NAS Colloquium) Virulence and Defense in Host--Pathogen Interactions Common Features Between Plants and Animals (2001) / Chapter Skim
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Bad Bugs and Beleaguered Bladders: Interplay Between Uropathogenic Escherichia coli and Innate Host Defenses
Bad Bugs and Beleaguered Bladders: Interplay Between Uropathogenic Escherichia coli and Innate Host Defenses
Pages 78-84
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From page 78... ...
Upon entering the urinary tract, UPEC strains face a formidable array of host defenses, including the flow of urine and a panoply of antimicrobial factors. To gain an initial foothold within the bladder, most UPEC strains encode filamentous surface adhesive organelles called type 1 pill that can mediate bacterial attachment to, and invasion of, bladder epithelial cells.
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From page 79... ...
The ability of type 1 pill to mediate bacterial attachment to the AUM of the facet cells lining the bladder lumen has been investigated by using a mouse cystitis model and microscopic techniques (13~. Shortly after inoculation of UPEC into mouse bladders, numerous bacteria can be found attached to the urothelial surface as detected by scanning electron microscopy (EM)
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From page 80... ...
This suggests that FimH can function as an invasin, a class of molecules, exemplified by the invasin protein encoded by Yersinia pseudotuberculosis and internalin A expressed by Listeria monocytogenes, that can mediate bacterial internalization into host cells in the absence of other virulence factors (24, 25~. Initial investigations have demonstrated that FimH-mediated bacterial invasion of bladder epithelial cells requires the activation of host signal transduction cascades involving protein tyrosine kineses, phosphoinositide-3 kinase, and localized host actin cytoskeletal rearrangements (23~.
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From page 81... ...
Rather than replicating, we have found that individual uropathogens can also apparently enter a quiescent state within host bladder epithelial cells. External cues, perhaps provided by the host cells, may effect whether intracellular UPEC enters a replicative or quiescent state.
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From page 82... ...
Indeed, it has been reported that soluble LPS can induce the exfoliation of single bladder cells and cell clusters when inoculated into mouse bladders from Albany or ICR mice (28, 29~. However, recent studies have shown that bladder epithelial cells in C3H/HeJ mice, which are nonresponsive to LPS, still exfoliate Mulvey et a/.
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From page 83... ...
P-pili can activate kidney epithelial cell cytokine production, independent of LPS, through a ceramide and serine/threonine kinase-dependent signaling pathway (42, 43~. In contrast, we have found that type 1 pill indirectly activate IL-6 production by bladder epithelial cells by mediating bacterial internalization, which in turn boosts bladder epithelial responses to LPS (J.D.S., M.A.M., R
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From page 84... ...
This could also facilitate the dissemination of UPEC within the urinary tract and help bacteria evade both innate and adaptive host defenses. Furthermore, exfoliation of bladder epithelial cells could leave lower layers of the urothelium more susceptible to infection.
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