| 1. |
- Dobrindt, Ulrich, et al.
(författare)
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Preface
- 2013
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Ingår i: Between Pathogenecity and Commensalism. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0070-217X. - 9783642365607 ; 358
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Bokkapitel (refereegranskat)
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| 2. |
- Adlerberth, Ingegerd, 1959, et al.
(författare)
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Adhesins of Escherichia coli associated with extra-intestinal pathogenicity confer binding to colonic epithelial cells.
- 1995
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Ingår i: Microbial pathogenesis. - 0882-4010. ; 18:6, s. 373-85
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli adhesins are virulence factors in intestinal and extra-intestinal infections, but their role in normal intestinal colonization has not been defined. We investigated the intestinal adherence of E. coli with Dr hemagglutinin, S fimbriae, CFA/I or CFA/II, using freshly isolated ileal or colonic enterocytes and cells from the human colonic cell line HT-29. E. coli with S-fimbrial adhesins (Sfa I or Sfa II), P or type 1 fimbriae, adhered in a non-polarized manner, and in similar numbers to colonic and ileal enterocytes. S fimbriae of the variety Sfa II (originating from a meningitis isolate), mediated a stronger binding than Sfa I (of uropathogenic origin). Strains expressing Dr hemagglutinin adhered preferentially to the brush borders, slightly better to colonic than ileal enterocytes. Strains expressing CFA/I or II adhered to colonic and ileal enterocytes, although brush border adherence was predominantly observed with ileal cells. Binding to HT-29 cells paralleled binding to colonic enterocytes for all adhesin specificities except CFA/I. The results suggest that Dr hemagglutinin, P-, type 1- and S-fimbrial adhesins mediate binding to both colonic and ileal enterocytes. These specificities may contribute to the establishment of E. coli in the intestinal microflora, which precedes their spread to extra-intestinal sites.
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| 3. |
- Adlerberth, Ingegerd, 1959, et al.
(författare)
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Interaction of P-fimbriated Escherichia coli with human meconium.
- 1991
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Ingår i: FEMS microbiology letters. - 0378-1097. ; 68:1, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- The ability of Escherichia coli with different receptor specificities to interact with meconium was studied. E. coli strains expressing P-fimbriae, specific for Gal alpha 1-4Gal beta-containing receptors, were agglutinated by meconium at high titres. This reaction was inhibited by globotetraosylceramide. The attachment of P-fimbriated E. coli to human colonic epithelial cells of the HT-29 cell line was inhibited by meconium. Some type 1 fimbriated strains were agglutinated by meconium, but the agglutination was rarely blocked by methyl alpha-D-mannoside. The attachment by type 1 fimbriated strains to HT-29 cells was reduced by meconium only in some cases. These results suggest that meconium interacts with the P-fimbriae of E. coli, in a way that may influence bacterial colonization of the neonatal intestine.
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| 4. |
- Adlerberth, Ingegerd, 1959, et al.
(författare)
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Intestinal colonization with Enterobacteriaceae in Pakistani and Swedish hospital-delivered infants.
- 1991
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Ingår i: Acta paediatrica Scandinavica. - 0001-656X. ; 80:6-7, s. 602-10
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Tidskriftsartikel (refereegranskat)abstract
- Rectal cultures from Swedish and Pakistani hospital-delivered newborn infants were analysed regarding the early acquisition of enterobacteria. Swedish infants were delivered vaginally, Pakistani infants were delivered either vaginally or by caesarean section. The Swedish infants were all breast-fed, whereas breastfeeding was incomplete and often started late among the Pakistani infants. Both groups of Pakistani infants were more rapidly colonized with enterobacteria than were the Swedish infants. Cultures from Swedish infants seldom yielded more than one kind of enterobacteria; E. coli and Klebsiella were most frequently isolated. E. coli dominated in both Pakistani groups, but especially caesarean section delivered infants were in addition often colonized with Proteus, Klebsiella, Enterobacter or Citrobacter species. Breastfeeding from the first day of life reduced colonization with Klebsiella/Enterobacter/Citrobacter. The results suggest that environmental exposure, delivery mode and early feeding habits all influence the early intestinal colonization with enterobacteria.
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| 5. |
- Ahmadi, Shahram, et al.
(författare)
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Similar immune responses to alpha1-oleate and Bacillus Calmette–Guérin treatment in patients with bladder cancer
- 2024
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Ingår i: Cancer Medicine. - 2045-7634. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: The molecular content of urine is defined by filtration in the kidneys and by local release from tissues lining the urinary tract. Pathological processes and different therapies change the molecular composition of urine and a variety of markers have been analyzed in patients with bladder cancer. The response to BCG immunotherapy and chemotherapy has been extensively studied and elevated urine concentrations of IL-1RA, IFN-α, IFN-γ TNF-α, and IL-17 have been associated with improved outcome. Methods: In this study, the host response to intravesical alpha 1-oleate treatment was characterized in patients with non-muscle invasive bladder cancer by proteomic and transcriptomic analysis. Results: Proteomic profiling detected a significant increase in multiple cytokines in the treatment group compared to placebo. The innate immune response was strongly activated, including IL-1RA and pro-inflammatory cytokines in the IL-1 family (IL-1α, IL-1β, IL-33), chemokines (MIP-1α, IL-8), and interferons (IFN-α2, IFN-γ). Adaptive immune mediators included IL-12, Granzyme B, CD40, PD-L1, and IL-17D, suggesting broad effects of alpha 1-oleate treatment on the tumor tissues. Conclusions: The cytokine response profile in alpha 1-oleate treated patients was similar to that reported in BCG treated patients, suggesting a significant overlap. A reduction in protein levels at the end of treatment coincided with inhibition of cancer-related gene expression in tissue biopsies, consistent with a positive treatment effect. Thus, in addition to killing tumor cells and inducing cell detachment, alpha 1-oleate is shown to activate a broad immune response with a protective potential.
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| 6. |
- Aits, Sonja, et al.
(författare)
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HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:5, s. 1008-1019
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Tidskriftsartikel (refereegranskat)abstract
- HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.
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| 7. |
- Ambite, Inès, et al.
(författare)
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Active bacterial modification of the host environment through RNA polymerase II inhibition
- 2021
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 131:4
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Tidskriftsartikel (refereegranskat)abstract
- Unlike pathogens, which attack the host, commensal bacteria create a state of friendly coexistence. Here, we identified a mechanism of bacterial adaptation to the host niche, where they reside. Asymptomatic carrier strains were shown to inhibit RNA polymerase II (Pol II) in host cells by targeting Ser2 phosphorylation, a step required for productive mRNA elongation. Assisted by a rare, spontaneous loss-of-function mutant from a human carrier, the bacterial NlpD protein was identified as a Pol II inhibitor. After internalization by host cells, NlpD was shown to target constituents of the Pol II phosphorylation complex (RPB1 and PAF1C), attenuating host gene expression. Therapeutic efficacy of a recombinant NlpD protein was demonstrated in a urinary tract infection model, by reduced tissue pathology, accelerated bacterial clearance, and attenuated Pol II-dependent gene expression. The findings suggest an intriguing, evolutionarily conserved mechanism for bacterial modulation of host gene expression, with a remarkable therapeutic potential.
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| 8. |
- Ambite, Ines, et al.
(författare)
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Bacterial suppression of RNA polymerase II-dependent host gene expression
- 2016
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Ingår i: Pathogens. - : MDPI AG. - 2076-0817. ; 5:3
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Forskningsöversikt (refereegranskat)abstract
- Asymptomatic bacteriuria (ABU) is a bacterial carrier state in the urinary tract that resembles commensalism at other mucosal sites. ABU strains often lack the virulence factors that characterize uropathogenic Escherichia coli (E. coli) strains and therefore elicit weak innate immune responses in the urinary tract. In addition, ABU strains are active modifiers of the host environment, which they influence by suppressing RNA polymerase II (Pol II)-dependent host gene expression. In patients inoculated with the ABU strain E. coli 83972, gene expression was markedly reduced after 24 h (>60% of all regulated genes). Specific repressors and activators of Pol II-dependent transcription were modified, and Pol II Serine 2 phosphorylation was significantly inhibited, indicating reduced activity of the polymerase. This active inhibition included disease–associated innate immune response pathways, defined by TLR4, IRF-3 and IRF-7, suggesting that ABU strains persist in human hosts by active suppression of the antibacterial defense. In a search for the mechanism of inhibition, we compared the whole genome sequences of E. coli 83972 and the uropathogenic strain E. coli CFT073. In addition to the known loss of virulence genes, we observed that the ABU strain has acquired several phages and identified the lytic Prophage 3 as a candidate Pol II inhibitor. Intact phage particles were released by ABU during in vitro growth in human urine. To address if Prophage 3 affects Pol II activity, we constructed a Prophage 3 negative deletion mutant in E. coli 83972 and compared the effect on Pol II phosphorylation between the mutant and the E. coli 83972 wild type (WT) strains. No difference was detected, suggesting that the Pol II inhibitor is not encoded by the phage. The review summarizes the evidence that the ABU strain E. coli 83972 modifies host gene expression by inhibition of Pol II phosphorylation, and discusses the ability of ABU strains to actively create an environment that enhances their persistence.
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| 9. |
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| 10. |
- Ambite, Ines, et al.
(författare)
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Fimbriae reprogram host gene expression - Divergent effects of P and type 1 fimbriae
- 2019
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 15:6, s. 1007671-1007671
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Tidskriftsartikel (refereegranskat)abstract
- Pathogens rely on a complex virulence gene repertoire to successfully attack their hosts. We were therefore surprised to find that a single fimbrial gene reconstitution can return the virulence-attenuated commensal strain Escherichia coli 83972 to virulence, defined by a disease phenotype in human hosts. E. coli 83972pap stably reprogrammed host gene expression, by activating an acute pyelonephritis-associated, IRF7-dependent gene network. The PapG protein was internalized by human kidney cells and served as a transcriptional agonist of IRF-7, IFN-β and MYC, suggesting direct involvement of the fimbrial adhesin in this process. IRF-7 was further identified as a potent upstream regulator (-log (p-value) = 61), consistent with the effects in inoculated patients. In contrast, E. coli 83972fim transiently attenuated overall gene expression in human hosts, enhancing the effects of E. coli 83972. The inhibition of RNA processing and ribosomal assembly indicated a homeostatic rather than a pathogenic end-point. In parallel, the expression of specific ion channels and neuropeptide gene networks was transiently enhanced, in a FimH-dependent manner. The studies were performed to establish protective asymptomatic bacteriuria in human hosts and the reconstituted E. coli 83972 variants were developed to improve bacterial fitness for the human urinary tract. Unexpectedly, P fimbriae were able to drive a disease response, suggesting that like oncogene addiction in cancer, pathogens may be addicted to single super-virulence factors.
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