Interaction of uropathogenic Escherichia coli with host uroepithelium
Introduction
The first step in the encounter between a host and pathogen is the attachment of the pathogen to the host epithelium by way of an interaction between an adhesin on the pathogen and a receptor on the host tissue. This contact initiates a dynamic molecular cross-talk that ultimately determines the outcome of the infectious process. The interaction between host and pathogen is one of the most complex and interesting fields of study in medicine. Further understanding of the host–pathogen interface has important implications for disease treatment and prevention.
The study of urinary tract infections (UTIs) has provided many insights into the molecular basis of host–pathogen interactions. UTIs are among the most common and troublesome bacterial infections, accounting for approximately seven million infections per year and over $1 billion in annual cost, making them a major public health concern [1]. These infections occur mostly in women and are usually caused by Escherichia coli, although other pathogens such as Staphylococcus saprophyticus, Enterococcus faecalis, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa infrequently cause disease [2]. An acute UTI caused by uropathogenic Escherichia coli (UPEC) can lead to recurrent infection, often by the same bacterial strain and despite antibiotic treatment [3]. The inability of current antimicrobial regimens to adequately address this problem suggests that our understanding of UTIs is incomplete. Although recurrent infections are typically thought of as being due to re-inoculation with a strain colonizing the gastrointestinal tract [4], another viable possibility is that bacteria from the original acute infection persist within the urinary tract.
In this review, we discuss the molecular interactions between UPEC and host epithelium and subsequent events in the pathogenesis of urinary tract infection.
Section snippets
The chaperone/usher pathway
Factors favoring the introduction of UPEC into the bladder include the proximity of the anus to the urethral opening in the human female, as well as sexual intercourse [1] and other unappreciated factors. The bacterial factors that aid in the ascent of UPEC from the urethral opening to the bladder are not known. Once UPEC arrives in the bladder, at least two adhesins, type 1 and P pili, are known to play crucial roles in the development of cystitis and pyelonephritis, respectively.
Pili are
Intracellular bacterial communities
The FimH-mediated interaction of UPEC with bladder epithelial cells triggers a signal transduction cascade that results in the uptake of the attached bacteria by superficial umbrella cells [20]. In a unique strategy to subvert epithelial barrier function, type 1 piliated bacteria enter bladder epithelial cells through an interaction with lipid rafts and uroplakins, the very components of the bladder epithelium that provide an impermeable layer necessary for bladder function [21]. In the murine
Host response
Upon UPEC infection, the host tissue responds by initiating defense pathways, leading to epithelial exfoliation and neutrophil influx. Exfoliation of the superficial facet cell layer begins within hours of infection and facilitates the elimination of infected cells into the urine [26]. Exfoliation and/or infection was found to trigger prominent changes in the transcriptional regulation of epithelial differentiation and proliferation, pro-inflammatory and apoptotic responses, and barrier
Conclusions
UTIs continue to represent a major public health problem, despite the availability of current antimicrobial therapies. Recent advances at the molecular level include the elucidation of the structural basis for contacts between primary bacterial virulence factors and key host epithelial receptors. At the microscopic level, the murine model of IBC formation and maturation offers a powerful system to examine the temporal and spatial expression of virulence determinants during cystitis. Synergy
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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Urosepsis
2022, Small Animal Critical Care MedicinePayload hardware and experimental protocol development to enable future testing of the effect of space microgravity on the resistance to gentamicin of uropathogenic Escherichia coli and its σ <sup>s</sup> -deficient mutant
2017, Life Sciences in Space ResearchCitation Excerpt :As in our previous work (Wang et al., 2014; Matin, 2009; Zgurskaya et al., 1997), our focus here is on stationary-phase UPEC. This is because: (a) due, for example, to lack of nutrients or the presence of oxidative stress, this late-growth phase is often experienced by bacteria in the human host (Matin, 2014; Hengge-Aronis, 2002a, Kolter et al., 1993); (b) it is in the stationary phase that bacteria express many of the virulence traits required for disease causation (Sonenshein, 2005; Llorens et al., 2010; Cabeen, 2014; Dalebroux et al., 2010; Mangan et al., 2006; Mouslim and Hughes, 2014; Roop et al., 2003) (an example is UPEC Type I fimbriae, which it uses in bladder colonization (Kau et al., 2005a, b)); and (c) bacteria in this phase are hard to eradicate, because the GSR activated in this phase makes bacteria broadly resistant (Matin, 1991, 2014). Nanosatellite systems, such as GeneSat, PharmaSat, and O/OREOS, were developed by NASA to augment the capability for studying microbial behavior in space MG over that offered by the Space Shuttle and the International Space Station (Nicholson et al., 2011; Woellert et al., 2011; Ricco et al., 2011).
Urinary Tract Infections, Renal Abscess, and Other Complex Renal Infections
2017, Principles and Practice of Pediatric Infectious DiseasesQuantification of filamentation by uropathogenic Escherichia coli during experimental bladder cell infection by using semi-automated image analysis
2015, Journal of Microbiological MethodsCitation Excerpt :UPEC filamentation during urinary tract infection (UTI) has been studied for the last decade (Horvath et al., 2011; Justice et al., 2004, 2006; Mulvey et al., 2001), and is suggested to occur as part of a so-called intracellular uropathogenic cascade (Justice et al., 2004). In this cyclic pathway UPEC invades the superficial bladder epithelial cell (BEC) layer, forms intracellular colonies and ultimately breaks out of the host cell in the form of highly filamentous bacteria (reviewed in Justice et al., 2008; Kau et al., 2005). By reverting back to its normal rod-shape through coordinated cell division each UPEC filament can give rise to multiple infectious single bacteria (Andersen et al., 2012; Justice et al., 2004), which can reinvade neighboring cells of the bladder epithelium.
Effects of single- and multi-strain probiotics on biofilm formation and invitro adhesion to bladder cells by urinary tract pathogens
2014, AnaerobeCitation Excerpt :This suggests that competition for nutrients and production of antagonistic compounds are potential mechanisms for the inhibition of UTI by probiotics, and that multi-strain treatments may provide extra benefits due to their species-specific effects on different pathogenic strains. Adherence to host cells is thought to be a major contributor to both E. faecalis [16] and E. coli pathogenesis [17,18], particularly with regard to UTI-causing strains [19]. Formation of biofilms is a major mechanism of attachment, in which a group of bacterial cells adhere to the host epithelium, covered with an extracellular polymer which protects the colony from environmental stresses such as changes to pH and temperature [20] and antibiotics [21].
Urosepsis
2014, Small Animal Critical Care Medicine, Second Edition