1. Home
  2. People Index
  3. Bernhard Hube

Bernhard Hube

About Bernhard Hube:
No description specified

SEEK ID: https://funginet.hki-jena.de/people/11

Location:  Germany

Expertise: Not specified

Tools: Not specified

ORCID: Not specified

project_administrator
help Bernhard's tags

This person has not yet tagged anything.

Related items

3 hidden items
3 hidden items
4 hidden items
Metabolic modeling predicts specific gut bacteria as key determinants for Candida albicans colonization levels.
INF, A5, C1, C2, B5

Abstract (Expand)

Candida albicans is a leading cause of life-threatening hospital-acquired infections and can lead to Candidemia with sepsis-like symptoms and high mortality rates. We reconstructed a genome-scale C. … albicans metabolic model to investigate bacterial-fungal metabolic interactions in the gut as determinants of fungal abundance. We optimized the predictive capacity of our model using wild type and mutant C. albicans growth data and used it for in silico metabolic interaction predictions. Our analysis of more than 900 paired fungal-bacterial metabolic models predicted key gut bacterial species modulating C. albicans colonization levels. Among the studied microbes, Alistipes putredinis was predicted to negatively affect C. albicans levels. We confirmed these findings by metagenomic sequencing of stool samples from 24 human subjects and by fungal growth experiments in bacterial spent media. Furthermore, our pairwise simulations guided us to specific metabolites with promoting or inhibitory effect to the fungus when exposed in defined media under carbon and nitrogen limitation. Our study demonstrates that in silico metabolic prediction can lead to the identification of gut microbiome features that can significantly affect potentially harmful levels of C. albicans.

Authors: Mohammad Mirhakkak, Sascha Schäuble, Tilman Klassert, S. Brunke, Philipp Brandt, D. Loos, R. V. Uribe, F. Senne de Oliveira Lino, Y. Ni, Slavena Vylkova, Hortense Slevogt, Bernhard Hube, Esther Weiß, M. O. A. Sommer, Gianni Panagiotou

Date Published: 15th Dec 2020

Journal: ISME J

Lysosome Fusion Maintains Phagosome Integrity during Fungal Infection.
C1

Abstract (Expand)

Phagosomes must maintain membrane integrity to exert their microbicidal function. Some microorganisms, however, survive and grow within phagosomes. In such instances, phagosomes must expand to avoid … rupture and microbial escape. We studied whether phagosomes regulate their size to preserve integrity during infection with the fungal pathogen Candida albicans. Phagosomes release calcium as C. albicans hyphae elongate, inducing lysosome recruitment and insertion, thereby increasing the phagosomal surface area. As hyphae grow, the expanding phagosome consumes the majority of free lysosomes. Simultaneously, lysosome biosynthesis is stimulated by activation of TFEB, a transcriptional regulator of lysosomal biogenesis. Preventing lysosomal insertion causes phagosomal rupture, NLRP3 inflammasome activation, IL-1beta secretion and host-cell death. Whole-genome transcriptomic analysis demonstrate that stress responses elicited in C. albicans upon engulfment are reversed if phagosome expansion is prevented. Our findings reveal a mechanism whereby phagosomes maintain integrity while expanding, ensuring that growing pathogens remain entrapped within this microbicidal compartment.

Authors: J. Westman, G. F. W. Walpole, Lydia Kasper, B. Y. Xue, O. Elshafee, Bernhard Hube, S. Grinstein

Date Published: 9th Dec 2020

Journal: Cell Host Microbe

The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives.
FungiNet C - Candida projects, C5

Abstract (Expand)

Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers … and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.

Authors: C. d'Enfert, A. K. Kaune, L. R. Alaban, S. Chakraborty, N. Cole, M. Delavy, D. Kosmala, B. Marsaux, R. Frois-Martins, M. Morelli, D. Rosati, M. Valentine, Z. Xie, Y. Emritloll, P. A. Warn, F. Bequet, M. E. Bougnoux, S. Bornes, Mark Gresnigt, Bernhard Hube, Ilse Jacobsen, M. Legrand, S. Leibundgut-Landmann, C. Manichanh, C. A. Munro, M. G. Netea, K. Queiroz, K. Roget, V. Thomas, C. Thoral, P. Van den Abbeele, A. W. Walker, A. J. P. Brown

Date Published: 24th Nov 2020

Journal: FEMS Microbiol Rev

Survival Strategies of Pathogenic Candida Species in Human Blood Show Independent and Specific Adaptations.
INF, B3 (E), C1, C3

Abstract (Expand)

Only four species, Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis, together account for about 90% of all Candida bloodstream infections and are among the most common causes of invasive … fungal infections of humans. However, virulence potential varies among these species, and the phylogenetic tree reveals that their pathogenicity may have emerged several times independently during evolution. We therefore tested these four species in a human whole-blood infection model to determine, via comprehensive dual-species RNA-sequencing analyses, which fungal infection strategies are conserved and which are recent evolutionary developments. The ex vivo infection progressed from initial immune cell interactions to nearly complete killing of all fungal cells. During the course of infection, we characterized important parameters of pathogen-host interactions, such as fungal survival, types of interacting immune cells, and cytokine release. On the transcriptional level, we obtained a predominantly uniform and species-independent human response governed by a strong upregulation of proinflammatory processes, which was downregulated at later time points after most of the fungal cells were killed. In stark contrast, we observed that the different fungal species pursued predominantly individual strategies and showed significantly different global transcriptome patterns. Among other findings, our functional analyses revealed that the fungal species relied on different metabolic pathways and virulence factors to survive the host-imposed stress. These data show that adaptation of Candida species as a response to the host is not a phylogenetic trait, but rather has likely evolved independently as a prerequisite to cause human infections.IMPORTANCE To ensure their survival, pathogens have to adapt immediately to new environments in their hosts, for example, during the transition from the gut to the bloodstream. Here, we investigated the basis of this adaptation in a group of fungal species which are among the most common causes of hospital-acquired infections, the Candida species. On the basis of a human whole-blood infection model, we studied which genes and processes are active over the course of an infection in both the host and four different Candida pathogens. Remarkably, we found that, while the human host response during the early phase of infection is predominantly uniform, the pathogens pursue largely individual strategies and each one regulates genes involved in largely disparate processes in the blood. Our results reveal that C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis all have developed individual strategies for survival in the host. This indicates that their pathogenicity in humans has evolved several times independently and that genes which are central for survival in the host for one species may be irrelevant in another.

Authors: P. Kammer, S. McNamara, Thomas Wolf, Theresia Conrad, Stefanie Allert, F. Gerwien, Kerstin Hünniger, Oliver Kurzai, Reinhard Guthke, Bernhard Hube, Jörg Linde, S. Brunke

Date Published: 6th Oct 2020

Journal: mBio

Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria.
INF, C1, B5

Abstract (Expand)

BACKGROUND: Antibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal … tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing. RESULTS: While the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate. CONCLUSIONS: We demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition. Video abstract.

Authors: Bastian Seelbinder, J. Chen, S. Brunke, R. Vazquez-Uribe, R. Santhaman, A. C. Meyer, F. S. de Oliveira Lino, K. F. Chan, D. Loos, L. Imamovic, C. C. Tsang, R. P. Lam, S. Sridhar, K. Kang, Bernhard Hube, P. C. Woo, M. O. A. Sommer, Gianni Panagiotou

Date Published: 12th Sep 2020

Journal: Microbiome

Molecular characterization of Candida albicans mucosal colonization, infection and translocation
FungiNet total

Talk at internal seminar in Jena_21.11.2017

Creators: Toni Förster, Selene Mogavero, Bernhard Hube, Lydia Kasper, Stefanie Allert

Contributor: Toni Förster

Download
Molecular characterization of Candida albicans mucosal colonization, infection and translocation
FungiNet C - Candida projects

FungiNet C1 Talk September 2017

Creators: Toni Förster, Stefanie Allert, Bernhard Hube, Selene Mogavero, Lydia Kasper, Christian Pérez, Juliane Meir

Contributor: Toni Förster

Download
5 hidden items
Powered by
 (v.1.9.1)
About INF | FungiNet | Funding and Programmes | Credits | Imprint
Copyright © 2008 - 2019 The University of Manchester and HITS gGmbH