WWW.DISSERTATION.XLIBX.INFO
FREE ELECTRONIC LIBRARY - Dissertations, online materials
 
<< HOME
CONTACTS



Pages:     | 1 | 2 || 4 | 5 |   ...   | 21 |

«(Über die Bedeutung der bakteriellen Genomplastizität für die Adaptation und Evolution asymptomatischer Bakteriurie (ABU) Escherichia coli ...»

-- [ Page 3 ] --

2.2.1. Virulence factors of uropathogenic E. coli   Adhesins   Adherence factors facilitate the colonization of the urinary tract and promote E. coli colonization and persistence in the colon or vagina, which may serve as a reservoir for ascending infection in the urinary tract (Johnson, 1991). They include fimbrial (fimbriae, pili) and afimbrial adhesins. Various adhesins have been identified and studied. The P-, type 1, S-, and F1C fimbriae exhibit a composite structure, consisting of a rod-shaped shaft of 6-7 nm in diameter comprising over a thousand major and minor subunits (Sauer et al., 2000). The adhesin is located at the very tip of the fimbriae, often connected with the shaft via the socalled adapter pilus (Schilling et al., 2001). The adhesin and some other minor subunits are responsible for the specific binding to carbohydrate moieties on the surface of eukaryotic cells, therefore contributing to specific adherence (Johnson, 1991). The synthesis, export, correct folding and ordered assembly during fimbrial biogenesis occurs in a coordinated manner (Smyth et al., 1996). The P-, S- and F1C-fimbriae are more exclusively associated with extraintestinal E. coli isolates and the tip of these adhesins recognizes carbohydrate moieties: Galα(1-4)Gal, α-sialyl-2,3-β-galactose, and GalNAcβ(1-4)Galβ, respectively (Johnson, 1991). P fimbriae are shown to induce strongly inflammatory response (Bergsten et al., 2005; Wullt et al., 2002).

Type 1 fimbriae are not only expressed by pathogenic strains, and there is no difference in fim gene frequency in more and less virulent strains in the urinary tract (Plos et al., 1991). This fimbrial type mediates adhesion to mannose-containing oligosaccharides, e.g. on bladder epithelial cells. Type 1 fimbriae promote attachment and virulence in the murine urinary tract infection model (Hagberg et al., 1983; Snyder et al., 2004). The fimbriae have been shown to enhance bacterial survival, to stimulate mucosal inflammation and to promote bacterial invasion (Anderson et al., 2003; Connell et al., 2000). Allelic variation exists in fimH, the gene for the lectin subunit of type I fimbriae. Sokurenko et al. (1997) have shown that type 1 fimbriae with different fimH alleles vary in their ability to recognize various mannosides and only those capable of mediating high levels of adhesion via mono-mannosyl residues are more capable of mediating E. coli adhesion to uroepithelial cells. Therefore, it seems that certain variants of type 1 fimbriae may contribute more than others to E. coli urovirulence.

20   Introduction 

Most of the UPEC strains express curli fimbriae. It is suggested that these fimbriae play a role only in the early phase of infection (e.g., adherence to periurethral skin surface), since they are frequently expressed only at 30 °C (Olsen et al., 1993). In the last years, isolates have been detected in which co-expression of curli fimbriae and cellulose occurs at 30 °C as well as at 37 °C (rdar morphotype), but the importance of this trait for the survival and colonization in the host organism remains unclear (Zogaj et al., 2001).

Flagella 

The bacterial flagellum is a long helical surface appendage composed of polymerized flagellin subunits encoded by fliC. Although it has never been proven, flagella-mediated motility has been hypothesized to play a role in the pathogenesis of UTI caused by UPEC (Emody et al., 2003). Lane et al. (2005) demonstrated that flagella and flagellum mediated motility/chemotaxis may not be absolutely required but contributes to the fitness of bacterium and therefore significantly enhance colonisation of the urinary tract by UPEC. The same group later demonstrated that UPEC indeed utilize flagellin to ascend the upper urinary tract and fliC mutant bacteria were able to colonize the bladder but were significantly attenuated in the kidneys (Lane et al., 2007). Flagella are also implicated in virulence of other E. coli pathotypes, by inducing interleukin 8 expression and Toll-like receptor 5 (TLR-5) activation upon adhesion of EPEC to epithelial cells in vitro (Giron et al., 2002). Moreover, flagella have been shown to contribute to the virulence of other uropathogens, such as Proteus mirabilis (Mobley et al., 1996).

Toxins   Toxins are prominent virulence factors of bacterial pathogens. Three toxins play a major role during UTI: the cytotoxic necrotizing factor 1 (CNF-1), the cytolethal distending toxin (CDT) and α-haemolysin.

The α-haemolysin is widely disseminated among pathogenic bacteria and widely distributed in UPEC as well as in EHEC isolates. The hly gene cluster encoding the toxin and the enzymes for its biosynthesis is located on PAIs or on plasmids. Secretion via the type I secretion pathway, a posttranslational maturation and the presence of a C-terminal calcium binding domain are characteristics of this pore-forming toxin (Johnson, 1991). α-hemolysin is able to lyse a broad range of host cells which probably contributes to inflammation, tissue injury, and impaired host defences (Cavalieri et al., 1984).

21   Introduction 

CDT is a secreted protein which has the capacity to inhibit cellular proliferation by inducing an irreversible cell cycle block at the G2/M position (Comayras et al., 1997). CDT is composed of three polypeptides (CdtA, B and C) which are all required for CDT activity. The direct role of the toxin in urinary tract infection, however, remains to be proven.





CNF-1 is widely distributed in extraintestinal pathogens and belongs to a toxin family which modifies Rho, a subfamily of small GTP-binding proteins that are regulators of the actin cytoskeleton (Aktories, 1997). The gene for CNF-1 is chromosomally located on different pathogenicity islands of UPEC (Blum et al., 1994). Eukaryotic cells intoxicated with CNF-1 exhibit membrane ruffling, formation of focal adhesions and actin stress fibers and DNA replication in absence of cell division.

Iron acquisition systems 

Iron is needed by all living cells. E. coli uses iron for oxygen transport and storage, DNA synthesis, electron transport, and metabolism of peroxides. Ferric iron is highly insoluble and almost all of this iron is complexed with host iron proteins. Part of the host response to infection is to further reduce the amount of iron available for the invading pathogen (Der Vartanian et al., 1992). Pathogens are able to counter the iron restriction imposed by their hosts through the use of siderophores. Siderophores can compete with host iron-binding proteins and several siderophore-based transport systems are known to be required for effective host colonisation. The genes coding for the biosynthesis of such iron-uptake systems in E. coli may be located on plasmids or on the chromosome. The gene clusters encoding the enzymes for enterobactin (ent) and the ferric dicitrate transport system (fec) have a commonly conserved localization in the E. coli core genome. However the fec gene cluster has been identified to be PAI-encoded in Shigella flexneri (Luck et al., 2001). The iuc operon coding for aerobactin is either located on plasmids (pColV) or on different genomic islands, whereas the yersiniabactin-encoding HPI (fyu/irp) is widely distributed among Enterobacteriaceae and shows a rather conserved chromosomal localization at the asnT gene. The chu system is a well-characterized haeme transport system that firstly has been found in the chromosome of EHEC O157:H7 strains (Torres and Payne, 1997). This system enables the bacteria to utilize iron directly from the haeme and is widely distributed among UPEC isolates (Wyckoff et al., 1998). The iro gene cluster (coding for the enzymes required for salmochelin biosynthesis), firstly described for Salmonella enterica (Baumler et al., 1996), is involved in the uptake of catecholate-type siderophore compounds. The iro genes are widely distributed among E. coli

–  –  –

isolates and can be chromosomally or plasmid-encoded (Dobrindt et al., 2003). The ability for iron acquisition of bacteria might be advantageous for their survival in the urinary tract, therefore it is considered an important fitness trait.

O-, K-antigens and serum resistance   Lipopolysaccharide (LPS) is a key component of the outer membrane of Gram-negative bacteria. It comprises three distinct regions: Lipid A, the oligosaccharide core, and commonly a long-chain polysaccharide O antigen that causes a smooth phenotype (Amor et al., 2000).

Lipid A is the most conserved part of LPS. It is connected to the core part, which links it to the O repeating units. The O repeating units are highly polymorphic, and more than 190 serologically distinguished forms in E. coli are known today (Orskov et al., 1977). Since LPS is located on the outer surface of bacterial cells, its expression is known to be responsible for many features of the cell surface of the Gram–negative bacteria, such as resistance to detergents, hydrophobic antibiotics, organic acids, serum complement factors, adherence to eukaryotic cells etc. (Barua et al., 2002; Jacques, 1996; Svanborg-Eden et al., 1987). It has been suggested that some of these characteristics, especially resistance to the bactericidal effect of the complement system, are dependent on the length of the O side chain (Porat et al., 1992). LPS is believed to significantly contribute to virulence by protecting bacteria from the bactericidal effect of serum complement (Reeves, 1995).

Capsular polysaccharides, more than 80 types of which have been described for E. coli, are linear polymers of repeating carbohydrate subunits that sometimes also include a prominent amino acid or lipid component. They coat the cell, interfering with O-antigen detection and protecting the cell from host defence mechanisms (Johnson, 1991). Zingler et al. (1993) reported that the most frequent K antigens determined in 253 UPEC isolates are K1 and K5 (31 % and 35 % of the cases respectively); nevertheless more than 26 different K-antigens were identified. The high prevalence of these two capsular serogroups is not astonishing, since both capsular oligosaccharides mimic human antigens by being antigenically and structurally similar to carbohydrates present in human glycosphingolipids, thus preventing effective immune response against bacteria expressing them. The K1 capsule is present in all MENEC isolates and contributes to the ability to cross of the blood-brain barrier (Kim, 2002).

–  –  –

2.3. Asymptomatic bacteriuria (ABU)   2.3.1. UTI versus ABU   While much effort was taken to characterise isolates and the virulence traits of bacteria causing symptomatic urinary tract infections (Brzuszkiewicz et al., 2006; Welch et al., 2002), not much is known why patients with ABU do not develop symptoms. The organisms recovered in many cases belong to the same types of bacteria that cause cystitis, the most common being E. coli (Raz, 2003). However, little is yet known about the difference between symptomatic and asymptomatic UTI in terms of pathogenesis, natural history and risk factors.

Hanson (1982) suggested that strains with decreased virulence may colonize the urine rather than cause asymptomatic infection. Hull et al. (1998) compared virulence factors of isolates from UTI and ABU with isolates from patients with a neuropathic bladder due to spinal cord and brain injury. This group reported that UTI isolates are more likely than ABU strains to be haemolytic and exhibit mannose-resistant hemagglutination of human erythrocytes. It has been also shown that adhesiveness to human urinary tract epithelial cells was high for E. coli strains isolated from patients with acute pyelonephritis and acute cystitis, and low for asymptomatic bacteriuria strains (Edén et al., 1979). Taken together, it has been suggested that there might exist differences in the virulence between UTI and ABU isolates. However, the molecular basis for this is unknown.

2.3.2. Escherichia coli strain 83972: a model ABU E. coli isolate 

Many uropathogenic E. coli isolates (e.g. strain 536, UTI89, CFT073, J96, NU14) are widely used as a model to investigate symptomatic UTIs. However, the only established prototypic ABU isolate is currently E. coli strain 83972. This strain has originally been isolated from a young Swedish girl, who carried it for at least three years without symptoms (Lindberg et al., 1975). Isolate 83972 belongs to the phylogenetic lineage B2 of E. coli indicating a close relatedness to the UPEC strains, which cause symptomatic UTI. Moreover, it belongs to the same sequence type as UPEC strain CFT073 and commensal E. coli Nissle 1917 (Zdziarski et al., 2008) (Fig. 2). The strain does not express classical UPEC virulence factors, but genotypic analysis has revealed that this E. coli possess a large number of virulenceassociated genes (Dobrindt et al., 2003). A recent genotypic analysis of selected pathogenicity factors of strain 83972 suggested that the loss of functional type 1, F1C, and P fimbriae was due to deletions or multiple point mutations (Klemm et al., 2006; Roos et al., 2006a).

–  –  –

Fig. 2: Phenotypic comparison of E. coli strains CFT073, Nissle 1917 and 83972. All these strains belong to the same sequence type, ST 73 (Dobrindt, U.).

  Strain 83972 has been successfully used as a prophylactic agent in patients with recurrent urinary tract infections (Andersson et al., 1991; Sunden et al., 2006). For this, the bladder of patients was deliberately colonised with a monoculture of E. coli 83972 and asymptomatic bacteriuria was established for up to three years (Wullt et al., 1998). In these cases successful long-term colonisation with strain 83972 prevented the establishment of symptomatic UTI.

Deliberate colonisation with this strain has also been shown to reduce the frequency of UTI in patients with a neurogenic bladder secondary to spinal cord injuries (Hull et al., 2000).



Pages:     | 1 | 2 || 4 | 5 |   ...   | 21 |


Similar works:

«The Peak Oil and Die-Off. Mat Savinar Part I: Introduction “Perhaps the sentiments contained in the following pages are not yet sufficiently fashionable to procure them general favor; a long habit of not thinking a thing wrong gives it a superficial appearance of being right, and raises at first a formidable outcry in defense of custom. But the tumult soon subsides. Time makes more converts than reason.” -Thomas Paine, Common Sense (1776) “For my part, whatever anguish of spirit it may...»

«TIMOTHY ELDRED AUTHOR OF PRAY21 4-HOUR YOUTH MINISTRY ESCAPING THE TRAP OF FULL-TIME YOUTH MINISTRY © 2010 Timothy Eldred International Standard Book Number: 978-0-9796551-2-8 Unless otherwise indicated, Scripture quotations are from: The Message by Eugene Petersen. © 1993, 1994, 1995, 1996, 2000, 2001, 2002. Used by permission of NavPress Publishing Group. Other Scripture quotations are from: The Holy Bible, New International Version® (NIV). © 1973, 1978, 1984 by International Bible...»

«Koncepcja przebiegu zimowej trasy Pomorską Drogą św. Jakuba etapami nr 21 i 22 Łebień – Łeba Izbica Opracowanie przygotowane w ramach projektu „RECReate – Revitalisation of the European Culture Route in the South Baltic Area”, finansowanego z środków Europejskiego Funduszu Rozwoju Regionalnego w ramach Programu Współpracy Transgranicznej Południowy Bałtyk. W latach 2011 – 2014. Lębork 2014 Opracowanie i Redakcja: Tadeusz Krawczyk przy współpracy: J. Bona, E. Boniecka,...»

«The Art of Price War: a Perspective from China Z. John Zhang and Dongsheng Zhou1 A price war is something to be avoided in the West. However, Chinese companies have earned a reputation for starting price wars. Many US companies know too well that the first sight of a Chinese company in a US market means a price war is coming: it always offers a price that is 30-50% lower than its closest competition (BusinessWeek 2004). By now, many US companies have a taste of that terrifying “China...»

«ASEAN Corporate Governance Scorecard Country Reports and Assessments 2012–2013 Joint Initiative of the ASEAN Capital Markets Forum and the Asian Development Bank ASEAN CorporAtE GovErNANCE SCorECArd Country Reports and Assessments 2012–2013 Joint Initiative of the ASEAN Capital Markets Forum and the Asian Development Bank © 2013 Asian Development Bank All rights reserved. Published 2013. Printed in the Philippines. ISBN 978-92-9254-069-2 (Print), 978-92-9254-070-8 (PDF) Publication Stock...»

«Cordarone® (amiodarone HCl) TABLETS Rx only DESCRIPTION Cordarone (amiodarone HCl) is a member of a new class of antiarrhythmic drugs with predominantly Class III (Vaughan Williams' classification) effects, available for oral administration as pink, scored tablets containing 200 mg of amiodarone hydrochloride. The inactive ingredients present are colloidal silicon dioxide, lactose, magnesium stearate, povidone, starch, and FD&C Red 40. Cordarone is a benzofuran derivative:...»

«              Determining  Motivations  Behind  Business  Involvement  in  the  Dolphin  SMART   Program      by     Julia  Goss       Advisor:  Dr.  Andy  Read     May  2013                                 Masters  project  submitted  in  partial  fulfillment  of  the     requirements  for  the  Master  of  Environmental  Management  degree  in  the   the  Nicholas  School  of  the...»

«Acevedo-Muñoz 1 ERNESTO R. ACEVEDO-MUÑOZ 710 36th St. Film Studies Program University of Colorado at Boulder Boulder, Colorado 80303 316 UCB, ATLAS 327 Phone: (303) 374-4690 Boulder, CO 80309-0316 Fax: (303) 492-1362 Phone: (303) 735-2322 Ernesto.Acevedo@Colorado.edu DOB: 19 July 1968: Aguada, Puerto Rico Nationality: Puerto Rico (USA) Ph.D. University of Iowa, Iowa City (Film Studies/Communication Studies), 1998 Dissertation: “Deconstructing nationalism: Luis Buñuel and the crisis of...»

«1 Grupo Compás – The Alloy Valve Stockist Alloy gate, globe, check, ball, and butterfly valves in duplex, 6moly SMO super duplex, alloy 20, monel, hastelloy, inconel, incoloy and titanium. Alloy Valves from stock Corrosion-resistant, high-alloy valves Duplex valves Super duplex valves Alloy 20 valves Hastelloy valves Inconel valves Incoloy valves Monel valves 6moly & 254 SMO valves Titanium valves Zirconium, Uranus, 904L valves Gate, globe, check, ball and butterfly valves Barcelona, Spain....»

«“En el lugar de las tunas empedernidas”: Tenochtitlan en las crónicas mestizas1 Valeria AÑÓN Universidad de Buenos Aires–Conicet/Idihcs (UNLP) RESUMEN Espacio, ciudad, desplazamiento, viaje han sido ejes fundamentales en los estudios literarios coloniales hispanoamericanos en las últimas décadas. En ese marco, la atención hacia las tradiciones discursivas occidentales, el peso de la retórica, las inflexiones humanistas en la historia y la filología han aportado nuevas miradas a un...»

«REVIEW ESSAY Narrating Sorcery in the Sahel Joseph Hellweg University of Virginia Paul Stoller and Cheryl Olkes. In Sorcery's Shadow: A Memoir of Apprenticeship among the Songhay of Niger. Chicago: University of + Chicago Press, 1987. Pp. xviii 236. $19.95 cloth, $12.95 paper. The authors of this anthropological memoir have made an indispensable contribution to West African ethnography by describing their participation in Songhay sorcery. Beginning in 1976, Stoller made a series of five trips...»

«Before the Federal Communications Commission Washington, D.C. 20554 Petition for Rulemaking to Amend the ) Commission’s Rules to Promote Expanded Free ) Access to Local Broadcast Television Stations ) RM 11752 Via Over-the-Air Reception, Internet Streaming, ) Or Other Means ) OPPOSITION OF THE NATIONAL ASSOCIATION OF BROADCASTERS August 14, 2015 Table of Contents I. INTRODUCTION II. MEDIACOM’S PETITION IS GROUNDED IN MULTIPLE UNSUPPORTED AND INACCURATE ASSERTIONS III. MEDIACOM’S PROPOSAL...»





 
<<  HOME   |    CONTACTS
2016 www.dissertation.xlibx.info - Dissertations, online materials

Materials of this site are available for review, all rights belong to their respective owners.
If you do not agree with the fact that your material is placed on this site, please, email us, we will within 1-2 business days delete him.