المؤلفون: Raquel Alonso-Roman, Antonia Last, Mohammad H. Mirhakkak, Jakob L. Sprague, Lars Möller, Peter Großmann, Katja Graf, Rena Gratz, Selene Mogavero, Slavena Vylkova, Gianni Panagiotou, Sascha Schäuble, Bernhard Hube, Mark S. Gresnigt

المصدر: Nature Communications, Vol 13, Iss 1, Pp 1-15 (2022)

مصطلحات موضوعية: Science

الوصف: Commensal bacteria such as Lactobacillus rhamnosus can inhibit the pathogenicity of the fungus Candida albicans. Here, Alonso-Roman et al. investigate the interplay between C. albicans, L. rhamnosus and intestinal epithelial cells, showing that changes in the metabolic environment, induced by the bacteria, trigger adaptations in C. albicans that reduce fungal pathogenicity.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/4b43000037904e2aabfc1a7cd0eee186Test

المؤلفون: Jakob L. Sprague, Lydia Kasper, Bernhard Hube

المصدر: Gut Microbes, Vol 14, Iss 1 (2022)

مصطلحات موضوعية: Candida albicans, intestinal translocation, dissemination, fungi, gut colonization, Diseases of the digestive system. Gastroenterology, RC799-869

الوصف: ABSTRACTCandida species are the most prevalent cause of invasive fungal infections, of which Candida albicans is the most common. Translocation across the epithelial barrier into the bloodstream by intestinal-colonizing C. albicans cells serves as the main source for systemic infections. Understanding the fungal mechanisms behind this process will give valuable insights on how to prevent such infections and keep C. albicans in the commensal state in patients with predisposing conditions. This review will focus on recent developments in characterizing fungal translocation mechanisms, compare what we know about enteric bacterial pathogens with C. albicans, and discuss the different proposed hypotheses for how C. albicans enters and disseminates through the bloodstream immediately following translocation.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1949-0976Test; https://doaj.org/toc/1949-0984Test

الوصول الحر: https://doaj.org/article/9a3eda3b70b74f6bb80f094e0042d9a9Test

المؤلفون: Jakob L. Sprague, Tim B. Schille, Stefanie Allert, Verena Trümper, Adrian Lier, Peter Großmann, Emily L. Priest, Antzela Tsavou, Gianni Panagiotou, Julian R. Naglik, Duncan Wilson, Sascha Schäuble, Lydia Kasper, Bernhard Hube

مصطلحات موضوعية: Medicine, Microbiology, Cell Biology, Molecular Biology, Physiology, Ecology, Immunology, Cancer, Science Policy, Infectious Diseases, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, process remain unclear, microbial mechanisms behind, human mucosal surfaces, full virulence potential, frequently causes infections, div >< p, certain predisposing conditions, opportunistic fungal pathogen, peptide toxin candidalysin, intestinal epithelial barrier, fungal zinc acquisition, intestinal epithelial cells, mediated barrier protection, restrict fungal translocation, candida albicans <, iecs limits candidalysin, iecs counteract damage

الوصف: Expression of the genes involved in zinc transport ( ZRT101 , ZRT2 , ZRT3 , ZRC1 ), zinc scavenging ( PRA1 ), and regulation of zinc acquisition genes ( ZAP1 ). Log 2 (fold-change) compares infected samples to the yeast pre-culture conditions on the left and medium-only samples to the yeast pre-culture conditions on the right. Asterisks indicate time points with significantly expression changes (DESeq2 p < 0.05). (TIF)

العلاقة: https://figshare.com/articles/figure/_i_C_i_i_albicans_i_zinc-associated_genes_are_more_highly_expressed_in_the_absence_of_IECs_/25328929Test

الإتاحة: https://doi.org/10.1371/journal.ppat.1012031.s001Test
https://figshare.com/articles/figure/_i_C_i_i_albicans_i_zinc-associated_genes_are_more_highly_expressed_in_the_absence_of_IECs_/25328929Test

المؤلفون: Jakob L. Sprague, Tim B. Schille, Stefanie Allert, Verena Trümper, Adrian Lier, Peter Großmann, Emily L. Priest, Antzela Tsavou, Gianni Panagiotou, Julian R. Naglik, Duncan Wilson, Sascha Schäuble, Lydia Kasper, Bernhard Hube

مصطلحات موضوعية: Medicine, Microbiology, Cell Biology, Molecular Biology, Physiology, Ecology, Immunology, Cancer, Science Policy, Infectious Diseases, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, process remain unclear, microbial mechanisms behind, human mucosal surfaces, full virulence potential, frequently causes infections, div >< p, certain predisposing conditions, opportunistic fungal pathogen, peptide toxin candidalysin, intestinal epithelial barrier, fungal zinc acquisition, intestinal epithelial cells, mediated barrier protection, restrict fungal translocation, candida albicans <, iecs limits candidalysin, iecs counteract damage

الوصف: Fold change in gene expression in C . albicans WT (BWP17) and ece1 Δ/Δ strains during incubation in cell culture medium for (A) ZRT101 , (B) ZRT2 , (C) PRA1 , (D) ZRT3 , and (E) ZRC1 . All values are shown as the mean with standard deviation. (TIF)

العلاقة: https://figshare.com/articles/figure/Loss_of_i_ECE1_i_has_no_effect_on_the_transcriptional_zinc_starvation_response_in_medium_only_/25328935Test

الإتاحة: https://doi.org/10.1371/journal.ppat.1012031.s003Test
https://figshare.com/articles/figure/Loss_of_i_ECE1_i_has_no_effect_on_the_transcriptional_zinc_starvation_response_in_medium_only_/25328935Test

المؤلفون: Jakob L. Sprague, Tim B. Schille, Stefanie Allert, Verena Trümper, Adrian Lier, Peter Großmann, Emily L. Priest, Antzela Tsavou, Gianni Panagiotou, Julian R. Naglik, Duncan Wilson, Sascha Schäuble, Lydia Kasper, Bernhard Hube

مصطلحات موضوعية: Medicine, Microbiology, Cell Biology, Molecular Biology, Physiology, Ecology, Immunology, Cancer, Science Policy, Infectious Diseases, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, process remain unclear, microbial mechanisms behind, human mucosal surfaces, full virulence potential, frequently causes infections, div >< p, certain predisposing conditions, opportunistic fungal pathogen, peptide toxin candidalysin, intestinal epithelial barrier, fungal zinc acquisition, intestinal epithelial cells, mediated barrier protection, restrict fungal translocation, candida albicans <, iecs limits candidalysin, iecs counteract damage

الوصف: (A) Confluent, differentiated C2BBe1 cells were infected with WT (BWP17) and ece1 Δ/Δ C . albicans for 6 h and the protein content was sampled. Proteins involved in the damage response of oral epithelial cells were detected with ACT1 serving as a control. n.d. = not determined. (B) Protein levels normalized to actin. For p38, MKP1, EPHA2, EGFR, and AKT the normalized protein level for the phosphorylated protein is presented relative to the total respective protein level. (TIF)

العلاقة: https://figshare.com/articles/figure/Western_blot_detection_of_immune_signaling_proteins_for_IECs_infected_with_WT_and_i_ece1_i_/25328944Test

الإتاحة: https://doi.org/10.1371/journal.ppat.1012031.s006Test
https://figshare.com/articles/figure/Western_blot_detection_of_immune_signaling_proteins_for_IECs_infected_with_WT_and_i_ece1_i_/25328944Test

المؤلفون: Jakob L. Sprague, Tim B. Schille, Stefanie Allert, Verena Trümper, Adrian Lier, Peter Großmann, Emily L. Priest, Antzela Tsavou, Gianni Panagiotou, Julian R. Naglik, Duncan Wilson, Sascha Schäuble, Lydia Kasper, Bernhard Hube

مصطلحات موضوعية: Medicine, Microbiology, Cell Biology, Molecular Biology, Physiology, Ecology, Immunology, Cancer, Science Policy, Infectious Diseases, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, process remain unclear, microbial mechanisms behind, human mucosal surfaces, full virulence potential, frequently causes infections, div >< p, certain predisposing conditions, opportunistic fungal pathogen, peptide toxin candidalysin, intestinal epithelial barrier, fungal zinc acquisition, intestinal epithelial cells, mediated barrier protection, restrict fungal translocation, candida albicans <, iecs limits candidalysin, iecs counteract damage

الوصف: Loss of ZRT101 , ZRT2 , or PRA1 did not significantly impact hypha formation. However, loss of ZRC1 significantly decreased hyphal length in C . albicans in cell culture medium after 6 h. All values are shown as the mean with standard deviation. Data were compared using a one-way ANOVA with a post-hoc Dunnett’s multiple comparisons test. Statistical significance: *, P ≤ 0.05. (TIF)

العلاقة: https://figshare.com/articles/figure/Loss_of_i_ZRC1_i_significantly_impairs_hyphal_growth_in_i_C_i_i_albicans_i_/25328932Test

الإتاحة: https://doi.org/10.1371/journal.ppat.1012031.s002Test
https://figshare.com/articles/figure/Loss_of_i_ZRC1_i_significantly_impairs_hyphal_growth_in_i_C_i_i_albicans_i_/25328932Test

المؤلفون: Jakob L. Sprague, Tim B. Schille, Stefanie Allert, Verena Trümper, Adrian Lier, Peter Großmann, Emily L. Priest, Antzela Tsavou, Gianni Panagiotou, Julian R. Naglik, Duncan Wilson, Sascha Schäuble, Lydia Kasper, Bernhard Hube

مصطلحات موضوعية: Medicine, Microbiology, Cell Biology, Molecular Biology, Physiology, Ecology, Immunology, Cancer, Science Policy, Infectious Diseases, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, process remain unclear, microbial mechanisms behind, human mucosal surfaces, full virulence potential, frequently causes infections, div >< p, certain predisposing conditions, opportunistic fungal pathogen, peptide toxin candidalysin, intestinal epithelial barrier, fungal zinc acquisition, intestinal epithelial cells, mediated barrier protection, restrict fungal translocation, candida albicans <, iecs limits candidalysin, iecs counteract damage

الوصف: Genes differentially expressed when comparing the non-damaging ece1 Δ/Δ and the non-filamentous efg1 ΔΔ/ cph1 ΔΔ strains to their respective WT strains ( ece1 Δ/Δ compared to WT (BWP17) and efg1 ΔΔ/ cph1 ΔΔ compared to WT (SC5314)). The data are shown as the Log 2 (fold-change) of infected cells with the different strains compared to uninfected IECs. Asterisks indicate genes with statistically significant differences in expression (DESeq2 p < 0.05). (TIFF)

العلاقة: https://figshare.com/articles/figure/Transcriptional_response_of_IECs_to_infection_with_non-damaging_and_non-filamentous_i_C_i_i_albicans_i_/25328941Test

الإتاحة: https://doi.org/10.1371/journal.ppat.1012031.s005Test
https://figshare.com/articles/figure/Transcriptional_response_of_IECs_to_infection_with_non-damaging_and_non-filamentous_i_C_i_i_albicans_i_/25328941Test

المؤلفون: Jakob L. Sprague, Tim B. Schille, Stefanie Allert, Verena Trümper, Adrian Lier, Peter Großmann, Emily L. Priest, Antzela Tsavou, Gianni Panagiotou, Julian R. Naglik, Duncan Wilson, Sascha Schäuble, Lydia Kasper, Bernhard Hube

مصطلحات موضوعية: Medicine, Microbiology, Cell Biology, Molecular Biology, Physiology, Ecology, Immunology, Cancer, Science Policy, Infectious Diseases, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, process remain unclear, microbial mechanisms behind, human mucosal surfaces, full virulence potential, frequently causes infections, div >< p, certain predisposing conditions, opportunistic fungal pathogen, peptide toxin candidalysin, intestinal epithelial barrier, fungal zinc acquisition, intestinal epithelial cells, mediated barrier protection, restrict fungal translocation, candida albicans <, iecs limits candidalysin, iecs counteract damage

الوصف: (A) Inhibition of NFκB activation using the high affinity NFκB activation inhibitor quinazoline (QNZ) increases the damage potential of C . albicans wildtype, but not for the non-filamentous efg1 ΔΔ/ cph1 ΔΔ strain or the non-damaging ece1 Δ/Δ strain towards C2BBe1 cells after 24 h. LDH release was adjusted by subtracting the release from uninfected and untreated host cells. (B) Inhibition of NFκB activation increases fungal translocation of C . albicans after 24 h across intestinal epithelial cells independent of damage potential. (C) Blocking NFκB activation significantly increases the breakdown of barrier integrity after 24 h of the intestinal epithelial cell layer for efg1 ΔΔ/ cph1 ΔΔ and ece1 Δ/Δ, with a similar but not significant effect on both WT strains. (D) E-cadherin protein levels normalized to GAPDH and presented relative to levels in untreated C2BBe1 cells. QNZ treatment further increased degradation of E-cadherin during infection with WT (SC5314) and ece1 Δ/Δ. (E) Fluorescent labeling of E-cadherin during C . albicans infection with and without QNZ treatment (scale bar = 50 μm). Inhibition of NFκB activation decreased the organization of E-cadherin at IEC borders upon infection with the ece1 Δ/Δ and both WT strains. Representative pictures for each strain and treatment condition are shown from 3 biological replicates with median score values in the inset for each strain and condition. All values are shown as the mean with standard deviation. Host-cell damage (A), fungal translocation (B), and barrier integrity (C) data were compared using a one-way ANOVA. Statistical significance for host-cell damage (A) and fungal translocation (B) data was determined with a post-hoc Tukey’s multiple comparisons test, while significance for the barrier integrity (C) data was determined using a post-hoc Šidák’s multiple comparisons test. Statistical significance: **, P ≤ 0.01; ****, P ≤ 0.0001.

العلاقة: https://figshare.com/articles/figure/NF_B_activation_limits_i_ECE1_i_-dependent_damage_and_paracellular_translocation_/25328980Test

الإتاحة: https://doi.org/10.1371/journal.ppat.1012031.g005Test
https://figshare.com/articles/figure/NF_B_activation_limits_i_ECE1_i_-dependent_damage_and_paracellular_translocation_/25328980Test

المؤلفون: Jakob L. Sprague, Tim B. Schille, Stefanie Allert, Verena Trümper, Adrian Lier, Peter Großmann, Emily L. Priest, Antzela Tsavou, Gianni Panagiotou, Julian R. Naglik, Duncan Wilson, Sascha Schäuble, Lydia Kasper, Bernhard Hube

مصطلحات موضوعية: Medicine, Microbiology, Cell Biology, Molecular Biology, Physiology, Ecology, Immunology, Cancer, Science Policy, Infectious Diseases, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, process remain unclear, microbial mechanisms behind, human mucosal surfaces, full virulence potential, frequently causes infections, div >< p, certain predisposing conditions, opportunistic fungal pathogen, peptide toxin candidalysin, intestinal epithelial barrier, fungal zinc acquisition, intestinal epithelial cells, mediated barrier protection, restrict fungal translocation, candida albicans <, iecs limits candidalysin, iecs counteract damage

الوصف: (A) Inhibition of NFκB activation using the NFκB inhibitor SC75741 at concentrations of either 2.5 or 5 μM increased the damage of WT (BWP17) C . albicans , but not for the ece1 Δ/Δ strains. LDH release was adjusted by subtracting the release from uninfected and untreated host cells. (B) NFκB inhibition using either concentration also decreased the barrier integrity during infection with both WT and ece1 Δ/Δ strains. (C) Fungal translocation was significantly increased during infection with both WT and ece1 Δ/Δ C . albicans upon inhibition of NFκB using both concentrations of SC75741. These results match those obtained with the high-affinity NFκB inhibitor quinazoline. All values are shown as the mean with standard deviation. Host-cell damage (A), barrier integrity (B), and fungal translocation (C) data were compared using a one-way ANOVA with a post-hoc Šidák’s multiple comparisons test. Statistical significance: *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001. (TIF)

العلاقة: https://figshare.com/articles/figure/Treatment_of_IECs_with_another_NF_B_inhibitor_increases_host_cell_damage_loss_of_barrier_integrity_and_fungal_translocation_/25328950Test

الإتاحة: https://doi.org/10.1371/journal.ppat.1012031.s008Test
https://figshare.com/articles/figure/Treatment_of_IECs_with_another_NF_B_inhibitor_increases_host_cell_damage_loss_of_barrier_integrity_and_fungal_translocation_/25328950Test

المؤلفون: Jakob L. Sprague, Tim B. Schille, Stefanie Allert, Verena Trümper, Adrian Lier, Peter Großmann, Emily L. Priest, Antzela Tsavou, Gianni Panagiotou, Julian R. Naglik, Duncan Wilson, Sascha Schäuble, Lydia Kasper, Bernhard Hube

مصطلحات موضوعية: Medicine, Microbiology, Cell Biology, Molecular Biology, Physiology, Ecology, Immunology, Cancer, Science Policy, Infectious Diseases, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, process remain unclear, microbial mechanisms behind, human mucosal surfaces, full virulence potential, frequently causes infections, div >< p, certain predisposing conditions, opportunistic fungal pathogen, peptide toxin candidalysin, intestinal epithelial barrier, fungal zinc acquisition, intestinal epithelial cells, mediated barrier protection, restrict fungal translocation, candida albicans <, iecs limits candidalysin, iecs counteract damage

الوصف: All data used to generate graphs for main text and supplementary figures. (XLSX)

العلاقة: https://figshare.com/articles/dataset/Source_data_/25328965Test

الإتاحة: https://doi.org/10.1371/journal.ppat.1012031.s013Test
https://figshare.com/articles/dataset/Source_data_/25328965Test