| 1. |
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| 2. |
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| 3. |
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| 4. |
- Uhlen, P., et al.
(författare)
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alpha-Haemolysin of uropathogenic E-coli induces Ca2+ oscillations in renal epithelial cells
- 2000
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 405:6787, s. 694-697
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Tidskriftsartikel (refereegranskat)abstract
- Pyelonephritis is one of the most common febrile diseases in children. If not treated appropriately, it causes irreversible renal damage and accounts for a large proportion of end stage renal failures(1). Renal scarring can occur in the absence of inflammatory cells, indicating that bacteria may have a direct signalling effect on renal cells(2). Intracellular calcium ([Ca2+](i)) oscillations can protect cells from the cytotoxic effects of prolonged increases in intracellular calcium(3,4). However, no pathophysiologically relevant protein that induces such oscillations has been identified. Here we show that infection by uropathogenic Escherichia coli induces a constant, low-frequency oscillatory [Ca2+](i) response in target primary rat renal epithelial cells induced by the secreted RTX (repeats-in-toxin) toxin alpha-haemolysin. The response depends on calcium influx through L-type calcium channels as well as from internal stores gated by inositol triphosphate. Internal calcium oscillations induced by alpha-haemolysin in a renal epithelial cell line stimulated production of cytokines interleukin (IL)-6 and IL-8. Our findings indicate a novel role for alpha-haemolysin in pyelonephritis: as an inducer of an oscillating second messenger response in target cells, which fine-tunes gene expression during the inflammatory response.
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| 5. |
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| 6. |
- Antypas, H, et al.
(författare)
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Rapid diagnostic assay for detection of cellulose in urine as biomarker for biofilm-related urinary tract infections
- 2018
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Ingår i: NPJ biofilms and microbiomes. - : Springer Science and Business Media LLC. - 2055-5008. ; 4, s. 26-
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Tidskriftsartikel (refereegranskat)abstract
- The ability of uropathogenic Escherichia coli (UPEC) to adopt a biofilm lifestyle in the urinary tract is suggested as one cause of recurrent urinary tract infections (UTIs). A clinical role of UPEC biofilm is further supported by the presence of bacterial aggregates in urine of UTI patients. Yet, no diagnostics exist to differentiate between the planktonic and biofilm lifestyle of bacteria. Here, we developed a rapid diagnostic assay for biofilm-related UTI, based on the detection of cellulose in urine. Cellulose, a component of biofilm extracellular matrix, is detected by a luminescent-conjugated oligothiophene, which emits a conformation-dependent fluorescence spectrum when bound to a target molecule. We first defined the cellulose-specific spectral signature in the extracellular matrix of UPEC biofilm colonies, and used these settings to detect cellulose in urine. To translate this optotracing assay for clinical use, we composed a workflow that enabled rapid isolation of urine sediment and screening for the presence of UPEC-derived cellulose in <45 min. Using multivariate analysis, we analyzed spectral information obtained between 464 and 508 nm by optotracing of urine from 182 UTI patients and 8 healthy volunteers. Cellulose was detected in 14.8% of UTI urine samples. Using cellulose as a biomarker for biofilm-related UTI, our data provide direct evidence that UPEC forms biofilm in the urinary tract. Clinical implementation of this rapid, non-invasive and user-friendly optotracing diagnostic assay will potentially aid clinicians in the design of effective antibiotic treatment.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Gastric mucosal recognition of Helicobacter pylori is independent of Toll-like receptor 4
- 2003
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Ingår i: J Infect Dis. - 0022-1899. ; 187:5, s. 829-36
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the interactions between Helicobacter pylori, which specializes in colonizing the mucin layer that covers the gastric mucosa, and primary gastric epithelial cells. The expression pattern of Toll-like receptors (TLRs) in primary gastric epithelial cells and cell lines was compared. Primary cells did not express TLR4, whereas all cell lines expressed a nonsignaling form of TLR4. Because other cells within the mucosa expressed TLR4, it was next investigated whether H. pylori can be recognized by TLR4--they cannot. Moreover, H. pylori infection of primary cells induced a regulated production of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha, whereas infection of cell lines only resulted in IL-8 production. The cytokine production in all cell types was strictly cag dependent. These findings indicate that, although the epithelium is important in directing the immune response against H. pylori infections, the response is independent of TLR4.
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| 11. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Identification of target tissue glycosphingolipid receptors for uropathogenic, F1C-fimbriated Escherichia coli and its role in mucosal inflammation
- 2002
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 277:20, s. 18198-205
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial adherence to mucosal cells is a key virulence trait of pathogenic bacteria. The type 1 fimbriae and the P-fimbriae of Escherichia coli have both been described to be important for the establishment of urinary tract infections. While P-fimbriae recognize kidney glycosphingolipids carrying the Galalpha4Gal determinant, type 1 fimbriae bind to the urothelial mannosylated glycoproteins uroplakin Ia and Ib. The F1C fimbriae are one additional type of fimbria correlated with uropathogenicity. Although it was identified 20 years ago its receptor has remained unidentified. Here we report that F1C-fimbriated bacteria selectively interact with two minor glycosphingolipids isolated from rat, canine, and human urinary tract. Binding-active compounds were isolated and characterized as galactosylceramide, and globotriaosylceramide, both with phytosphingosine and hydroxy fatty acids. Comparison with reference glycosphingolipids revealed that the receptor specificity is dependent on the ceramide composition. Galactosylceramide was present in the bladder, urethers, and kidney while globotriaosylceramide was present only in the kidney. Using a functional assay, we demonstrate that binding of F1C-fimbriated Escherichia coli to renal cells induces interleukin-8 production, thus suggesting a role for F1C-mediated attachment in mucosal defense against bacterial infections.
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| 12. |
- Hornef, MW, et al.
(författare)
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Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells
- 2002
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 195:5, s. 559-570
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Tidskriftsartikel (refereegranskat)abstract
- Toll-like receptor (TLR) 4 is mainly found on cells of the myelopoietic lineage. It recognizes lipopolysaccharide (LPS) and mediates cellular activation and production of proinflammatory cytokines. Less is known about the distribution and role of TLR4 in epithelial cells that are continuously exposed to microbes and microbial products. Here we show that the murine small intestinal epithelial cell line m-ICcl2 is highly responsive to LPS and expresses both CD14 and TLR4. Transcription and surface membrane staining for CD14 were up-regulated upon LPS exposure. Surprisingly, TLR4 immunostaining revealed a strictly cytoplasmic paranuclear distribution. This paranuclear compartment could be identified as the Golgi apparatus. LPS added to the supernatant was internalized by m-ICcl2 cells and colocalized with TLR4. Continuous exposure to LPS led to a tolerant phenotype but did not alter TLR4 expression nor cellular distribution. Thus, intestinal epithelial cells might be able to provide the initial proinflammatory signal to attract professional immune cells to the side of infection. The cytoplasmic location of TLR4, which is identical to the final location of internalized LPS, further indicates an important role of cellular internalization and cytoplasmic traffic in the process of innate immune recognition.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Antypas, H., et al.
(författare)
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A universal platform for selection and high-resolution phenotypic screening of bacterial mutants using the nanowell slide
- 2018
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Ingår i: Lab on a Chip. - : ROYAL SOC CHEMISTRY. - 1473-0197 .- 1473-0189. ; 18:12, s. 1767-1777
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Tidskriftsartikel (refereegranskat)abstract
- The Petri dish and microtiter plate are the golden standard for selection and screening of bacteria in microbiological research. To improve on the limited resolution and throughput of these methods, we developed a universal, user-friendly platform for selection and high-resolution phenotypic screening based on the nanowell slide. This miniaturized platform has an optimal ratio between throughput and assay complexity, holding 672 nanowells of 500 nl each. As monoclonality is essential in bacterial genetics, we used FACS to inoculate each nanowell with a single bacterium in 15 min. We further extended the protocol to select and sort only bacteria of interest from a mixed culture. We demonstrated this by isolating single transposon mutants generated by a custom-made transposon with dual selection for GFP fluorescence and kanamycin resistance. Optical compatibility of the nanowell slide enabled phenotypic screening of sorted mutants by spectrophotometric recording during incubation. By processing the absorbance data with our custom algorithm, a phenotypic screen for growth-associated mutations was performed. Alternatively, by processing fluorescence data, we detected metabolism-associated mutations, exemplified by a screen for -galactosidase activity. Besides spectrophotometry, optical compatibility enabled us to perform microscopic analysis directly in the nanowells to screen for mutants with altered morphologies. Despite the miniaturized format, easy transition from nano- to macroscale cultures allowed retrieval of bacterial mutants for downstream genetic analysis, demonstrated here by a cloning-free single-primer PCR protocol. Taken together, our FACS-linked nanowell slide replaces manual selection of mutants on agar plates, and enables combined selection and phenotypic screening in a one-step process. The versatility of the nanowell slide, and the modular workflow built on mainstream technologies, makes our universal platform widely applicable in microbiological research.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Helicobacter pylori infection induces interleukin-8 receptor expression in the human gastric epithelium
- 2003
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Ingår i: Infect Immun. - 0019-9567. ; 71:6, s. 3357-60
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Tidskriftsartikel (refereegranskat)abstract
- The gastric pathogen Helicobacter pylori is known to activate multiple proinflammatory signaling pathways in epithelial cells. In this study, we addressed the question of whether expression of the interleukin-8 receptors IL-8RA (CXCR1) and IL-8RB (CXCR2) is upregulated in H. pylori-infected human gastric biopsy samples. Biopsy samples from patients infected with H. pylori strains harboring the cag pathogenicity island (PAI) expressed larger amounts of both receptors. In addition, IL-8RB expression was induced in the gastric epithelial cell line AGS upon infection with a clinical isolate containing the cag PAI, while a strain lacking the cag PAI did not. Our finding suggests that gastric epithelial cells express IL-8R in response to H. pylori infection.
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| 25. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Induction of innate immune responses by Escherichia coli and purified lipopolysaccharide correlate with organ- and cell-specific expression of Toll-like receptors within the human urinary tract
- 2001
-
Ingår i: Cell Microbiol. - 1462-5814. ; 3:3, s. 153-8
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal epithelial linings function as physical barriers against microbes. In addition, they participate in the first line of host defence by production of a variety of proinflammatory mediators when exposed to microbes and microbial agents. Here, we use a human urinary tract infection model to demonstrate that organ- and cell-specific innate responses induced by lipopolysaccharides (LPS) present on Gram-negative bacteria correlates with the expression of Toll-like receptor 4 (TLR4). The presence of TLR4 on human bladder epithelial cells enables them to rapidly respond to bacterial infections in vitro and in vivo. In contrast, TLR4 is not expressed on human proximal tubule cells isolated from the renal cortex, which may explain the cortical localization of bacteria in pyelonephritis. TLR4-negative renal epithelial cells, A498, are non-responsive to purified LPS, however, they respond to viable bacteria via a mannose-sensitive attachment-mediated pathway. To identify LPS components recognised by bladder epithelial cells, a bacterial lipid A mutant and LPS of different chemotypes were tested. Full interleukin 8 induction required hexa-acylated lipid A and was decreased by between 50% and 70% in the presence of O-antigen. Taken together, we propose that multiple independent pathways, which are organ- and cell-specifically expressed, mediate bacterial recognition and determine the outcome of innate responses to infection.
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| 26. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Structural requirements for TLR4-mediated LPS signalling: a biological role for LPS modifications
- 2003
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Ingår i: Microbes Infect. - 1286-4579 .- 1769-714X. ; 5:12, s. 1057-63
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Tidskriftsartikel (refereegranskat)abstract
- Cells of the mucosal lining are the first to encounter invading bacteria during infection, and as such, they have developed numerous ways of detecting microbial intruders. Recently, we showed that epithelial cells recognize lipopolysaccharide (LPS) through the CD14-Toll-like receptor (TLR)-4 complex. Here, we identify the substructures of LPS that are recognized by the TLR4 receptor complex. In contrast to lipid A, the O-antigen does not mediate an inflammatory response; rather it interferes with the lipid A recognition. An Escherichia coli strain genetically modified to express penta-acylated lipid A not only showed reduced immunogenicity, but was also found to inhibit pro-inflammatory signalling induced by wild-type E. coli (hexa-acylated lipid A) as well as LPS from other bacteria of the Enterobacteriaceae family. Furthermore, penta-acylated LPS from Pseudomonas aeruginosa acted as an antagonist to hexa-acylated E. coli LPS, as did E. coli, as shown by its inhibitory effect on IL-8 production in stimulated cells. Hypo-acylated lipid A, such as that of P. aeruginosa, is found in several species within the gut microflora as well as in several bacteria causing chronic infections. Thus, our results suggest that the composition of the microflora may be important in modulating pro-inflammatory signalling in epithelial cells under normal as well as pathologic conditions.
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| 27. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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TLR4-dependent recognition of lipopolysaccharide by epithelial cells requires sCD14
- 2002
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Ingår i: Cell Microbiol. - 1462-5814. ; 4:8, s. 493-501
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial cells lining the urinary bladder mucosa are engaged in numerous functions that act in concert to prevent exposure of the sensitive upper urinary tract to bacteria. This protective effect was recently suggested to be achieved mainly by compartmentalized, organ-specific expression of the lipopolysaccharide (LPS) receptor Toll-like receptor (TLR) 4 within epithelial cells of the urogenital tract. Here, we show that bladder epithelial cells recognize similarly low amounts of LPS as macrophages. LPS responsiveness measured as secretion of the chemoattractant interleukin 8 demonstrates a dependency on TLR4 in epithelial cells, which is similar to the situation in macrophages. The TLR4-mediated LPS response in bladder epithelial cells also uses the co-receptor CD14 for efficient LPS signalling. However, bladder epithelial cells do not express endogenous CD14 and are therefore dependent on the soluble form of CD14 that is present in body fluids. Furthermore, we demonstrate that epithelial chemokine production is augmented by type 1-mediated attachment of uropathogenic Escherichia coli in the absence, but not in the presence, of CD14. Collectively, our findings strengthen the role for bladder epithelial cells as important players in the innate immune system within the urinary tract.
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| 28. |
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| 29. |
- Choong, FX, et al.
(författare)
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Intravital models of infection lay the foundation for tissue microbiology
- 2012
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Ingår i: Future microbiology. - : Future Medicine Ltd. - 1746-0921 .- 1746-0913. ; 7:4, s. 519-533
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Tidskriftsartikel (refereegranskat)abstract
- In complex environments, such as those found in the human host, pathogenic bacteria constantly battle the unfavorable conditions imposed by the host response to their presence. During Escherichia coli-induced pyelonephritis, a cascade of events are shown in an intravital animal model to occur in a timely and sequential manner, representing the dynamic interplay between host and pathogen. Today, intravital techniques allow for observing infection in the living host. At resolutions almost on the single-cell level, improved detection methods offer a movie-like description of infection dynamics. Tissue microbiology involves monitoring host–pathogen interaction within the dynamic microecology of infectious sites in the live host. This new field holds great promise for insightful research into microbial disease intervention strategies.
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| 30. |
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| 31. |
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| 32. |
- Choong, FX, et al.
(författare)
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Real-time optotracing of curli and cellulose in live Salmonella biofilms using luminescent oligothiophenes
- 2016
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Ingår i: NPJ biofilms and microbiomes. - : Springer Science and Business Media LLC. - 2055-5008. ; 2, s. 16024-
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular matrix (ECM) is the protein- and polysaccharide-rich backbone of bacterial biofilms that provides a defensive barrier in clinical, environmental and industrial settings. Understanding the dynamics of biofilm formation in native environments has been hindered by a lack of research tools. Here we report a method for simultaneous, real-time, in situ detection and differentiation of the Salmonella ECM components curli and cellulose, using non-toxic, luminescent conjugated oligothiophenes (LCOs). These flexible conjugated polymers emit a conformation-dependent fluorescence spectrum, which we use to kinetically define extracellular appearance of curli fibres and cellulose polysaccharides during bacterial growth. The scope of this technique is demonstrated by defining biofilm morphotypes of Salmonella enterica serovars Enteritidis and Typhimurium, and their isogenic mutants in liquid culture and on solid media, and by visualising the ECM components in native biofilms. Our reported use of LCOs across a number of platforms, including intracellular cellulose production in eukaryotic cells and in infected tissues, demonstrates the versatility of this optotracing technology, and its ability to redefine biofilm research.
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| 33. |
- Eckert, Johannes A., et al.
(författare)
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An optotracer-based antibiotic susceptibility test specifically targeting the biofilm lifestyle of Salmonella
- 2022
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Ingår i: Biofilm. - : Elsevier BV. - 2590-2075. ; 4, s. 100083-
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance is a medical threat of global dimensions. Proper antimicrobial susceptibility testing (AST) for drug development, patient diagnosis and treatment is crucial to counteract ineffective drug use and resistance development. Despite the important role of bacterial biofilms in chronic and device-associated in-fections, the efficacy of antibiotics is determined using planktonic cultures. To address the need for antibiotics targeting bacteria in the biofilm lifestyle, we here present an optotracing-based biofilm-AST using Salmonella as model. Our non-disruptive method enables real-time recording of the extracellular matrix (ECM) components, providing specific detection of the biofilm lifestyle. Biofilm formation prior to antibiotic challenge can thus be confirmed and pre-treatment data collected. By introducing Kirby-Bauer discs, we performed a broad screen of the effects of antibiotics representing multiple classes, and identified compounds with ECM inhibitory as well as promoting effects. These compounds were further tested in agar-based dose-response biofilm-AST assays. By quantifying the ECM based on the amount of curli, and by visualizing the biofilm size and morphology, we achieved new information directly reflecting the treated biofilm. This verified the efficacy of several antibiotics that were effective in eradicating pre-formed biofilms, and it uncovered intriguing possible resistance mecha-nisms initiated in response to treatments. By providing deeper insights into the resistances and susceptibilities of microbes, expanded use of the biofilm-AST will contribute to more effective treatments of infections and reduced resistance development.
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| 34. |
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| 35. |
- Gomez-Carretero, S., et al.
(författare)
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Correction: Redox-active conducting polymers modulate Salmonella biofilm formation by controlling availability of electron acceptors (vol 3, article number 19, 2017)
- 2018
-
Ingår i: npj Biofilms and Microbiomes. - : Nature Publishing Group. - 2055-5008. ; 4:1
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In the original published article, the author list did not include Karl Svennersten, Kristin Persson, Edwin Jager and Magnus Berggren. After publication, we were notified by the corresponding author that the author list did not accurately reflect the contributions made, and these authors have been added to the author list. The original “Author Contributions” stated that “S.G.C., M.R., and A.R.D. designed research; S.G.C. performed all experiments…” this has been updated to read “S.G.C., K.S., K.M.P., E.W.H.J., M.B., M.R., and A.R.D. designed research; K.S., K.M.P., and E.W.H.J. performed experiments; S.G.C. performed all reported experiments…”. The “Acknowledgements” previously read “We thank K. Svennersten, A. Kader, K. Persson, and M. Berggren for fruitful discussions, and S. Löffler for insightful comments on the manuscript…” and have been updated to state “We thank A. Kader for fruitful discussions and S. Loffler for insightful comments on the manuscript…”. The “Competing Interests” section did not require any amendments. All authors have agreed with this correction statement and authorship change.
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| 36. |
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| 37. |
- Gomez-Carretero, S, et al.
(författare)
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Redox-active conducting polymers modulate Salmonella biofilm formation by controlling availability of electron acceptors
- 2017
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Ingår i: NPJ biofilms and microbiomes. - : Springer Science and Business Media LLC. - 2055-5008. ; 3, s. 19-
-
Tidskriftsartikel (refereegranskat)abstract
- Biofouling is a major problem caused by bacteria colonizing abiotic surfaces, such as medical devices. Biofilms are formed as the bacterial metabolism adapts to an attached growth state. We studied whether bacterial metabolism, hence biofilm formation, can be modulated in electrochemically active surfaces using the conducting conjugated polymer poly(3,4-ethylenedioxythiophene) (PEDOT). We fabricated composites of PEDOT doped with either heparin, dodecyl benzene sulfonate or chloride, and identified the fabrication parameters so that the electrochemical redox state is the main distinct factor influencing biofilm growth. PEDOT surfaces fitted into a custom-designed culturing device allowed for redox switching in Salmonella cultures, leading to oxidized or reduced electrodes. Similarly large biofilm growth was found on the oxidized anodes and on conventional polyester. In contrast, biofilm was significantly decreased (52–58%) on the reduced cathodes. Quantification of electrochromism in unswitched conducting polymer surfaces revealed a bacteria-driven electrochemical reduction of PEDOT. As a result, unswitched PEDOT acquired an analogous electrochemical state to the externally reduced cathode, explaining the similarly decreased biofilm growth on reduced cathodes and unswitched surfaces. Collectively, our findings reveal two opposing effects affecting biofilm formation. While the oxidized PEDOT anode constitutes a renewable electron sink that promotes biofilm growth, reduction of PEDOT by a power source or by bacteria largely suppresses biofilm formation. Modulating bacterial metabolism using the redox state of electroactive surfaces constitutes an unexplored method with applications spanning from antifouling coatings and microbial fuel cells to the study of the role of bacterial respiration during infection.
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| 38. |
- Gomez-Carretero, S., et al.
(författare)
-
Redox-active conducting polymers modulate Salmonella biofilm formation by controlling availability of electron acceptors (vol 3, article number 19, 2017)
- 2017
-
Ingår i: npj Biofilms and Microbiomes. - : Springer Science and Business Media LLC. - 2055-5008. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- Biofouling is a major problem caused by bacteria colonizing abiotic surfaces, such as medical devices. Biofilms are formed as the bacterial metabolism adapts to an attached growth state. We studied whether bacterial metabolism, hence biofilm formation, can be modulated in electrochemically active surfaces using the conducting conjugated polymer poly(3,4-ethylenedioxythiophene) (PEDOT). We fabricated composites of PEDOT doped with either heparin, dodecyl benzene sulfonate or chloride, and identified the fabrication parameters so that the electrochemical redox state is the main distinct factor influencing biofilm growth. PEDOT surfaces fitted into a custom-designed culturing device allowed for redox switching in Salmonella cultures, leading to oxidized or reduced electrodes. Similarly large biofilm growth was found on the oxidized anodes and on conventional polyester. In contrast, biofilm was significantly decreased (52-58%) on the reduced cathodes. Quantification of electrochromism in unswitched conducting polymer surfaces revealed a bacteria-driven electrochemical reduction of PEDOT. As a result, unswitched PEDOT acquired an analogous electrochemical state to the externally reduced cathode, explaining the similarly decreased biofilm growth on reduced cathodes and unswitched surfaces. Collectively, our findings reveal two opposing effects affecting biofilm formation. While the oxidized PEDOT anode constitutes a renewable electron sink that promotes biofilm growth, reduction of PEDOT by a power source or by bacteria largely suppresses biofilm formation. Modulating bacterial metabolism using the redox state of electroactive surfaces constitutes an unexplored method with applications spanning from antifouling coatings and microbial fuel cells to the study of the role of bacterial respiration during infection.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Loffler, S, et al.
(författare)
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Organic bioelectronics in infection
- 2015
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry (RSC). - 2050-7518 .- 2050-750X. ; 3:25, s. 4979-4992
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Tidskriftsartikel (refereegranskat)abstract
- Organic bioelectronics for dynamic modulation of normal and infected tissue microenvironments, and the development towards fully automated cell culture systems.
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| 46. |
- Loffler, S., et al.
(författare)
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Organic bioelectronics in medicine
- 2017
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Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 282:1, s. 24-36
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in the growing field of bioelectronic medicine is the development of tissue interface technologies promoting device integration with biological tissues. Materials based on organic bioelectronics show great promise due to a unique combination of electronic and ionic conductivity properties. In this review, we outline exciting developments in the field of organic bioelectronics and demonstrate the medical importance of these active, electronically controllable materials. Importantly, organic bioelectronics offer a means to control cell-surface attachment as required for many device-tissue applications. Experiments have shown that cells readily attach and proliferate on reduced but not oxidized organic bioelectronic materials. In another application, the active properties of organic bioelectronics were used to develop electronically triggered systems for drug release. After incorporating drugs by advanced loading strategies, small compound drugs were released upon electrochemical trigger, independent of charge. Another type of delivery device was used to achieve well-controlled, spatiotemporal delivery of cationic drugs. Via electrophoretic transport within a polymer, cations were delivered with single-cell precision. Finally, organic bioelectronic materials are commonly used as electrode coatings improving the electrical properties of recording and stimulation electrodes. Because such coatings drastically reduce the electrode impedance, smaller electrodes with improved signal-to-noise ratio can be fabricated. Thus, rapid technological advancement combined with the creation of tiny electronic devices reacting to changes in the tissue environment helps to promote the transition from standard pharmaceutical therapy to treatment based on electroceuticals. Moreover, the widening repertoire of organic bioelectronics will expand the options for true biological interfaces, providing the basis for personalized bioelectronic medicine.
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| 47. |
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| 48. |
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| 49. |
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| 50. |
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