Bernhard Hube

Bernhard Hube
Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute | HKI · Department of Microbial Pathogenicity Mechanisms

PhD

About

546
Publications
63,526
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22,184
Citations
Citations since 2016
150 Research Items
11412 Citations
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201620172018201920202021202205001,0001,500
201620172018201920202021202205001,0001,500
Introduction
Bernhard Hube is Head of the Department of "Microbial Pathogenicity Mechanisms" at the Hans Knoell Institute (HKI), a German Leibniz Institute which investigates the infection biology of human pathogenic fungi, and Professor at the Friedrich Schiller University (FSU) of Jena, Germany. His major research interest are the molecular pathogenicity mechanisms of infections with Candida albicans and C. glabrata. Webpage: www.leibniz-hki.de
Additional affiliations
January 2007 - present
Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute
Position
  • Head of Department and Chair Microbial Pathogenicity
Description
  • Current research is focussed on fungal functional genomics, host-pathogen interactions, infection models, extracellular enzymes, regulatory proteases, morphology, virulence associated genes, iron and zinc acquisition, and microevolution.
January 2007 - present
Friedrich Schiller University Jena
Position
  • Chair Microbial Pathogenicity
November 2006 - present
Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute
Position
  • Head of Department

Publications

Publications (546)
Article
Human fungal pathogens are a commonly underestimated cause of severe diseases associated with high morbidity and mortality. Like other pathogens, their survival and growth in the host, as well as subsequent host damage, is thought to be mediated by virulence factors which set them apart from harmless microbes. In this review, we describe and discus...
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Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Such toxins have not been identified previously in human pathogenic fungi. Here we identify the first, to our knowledge, fungal cytolytic peptide...
Article
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Multiple types of microbial infections in humans are caused by viruses, bacteria, fungi, or parasites. The outcome of these infections is largely determined by the genomes of the pathogen and host and the appropriate expression of their genes. As both host and microbe have to dynamically respond to changing conditions during the course of an infect...
Article
Candida glabrata is a successful human opportunistic pathogen which causes superficial but also life-threatening systemic infections. During infection, C. glabrata has to cope with cells of the innate immune system such as macrophages, which belong to the first line of defense against invading pathogens. C. glabrata is able to survive and even repl...
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Candida species are a major cause of invasive fungal infections. While Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis are the most dominant species causing life-threatening candidiasis, C. auris recently emerged as a new species causing invasive infections with high rates of clinical treatment failures. To mimic initial phases of...
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Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Fungal infections represent a serious burden on human health. Increasing numbers of susceptible hosts, a limited set of approved antifungal drugs which frequently trigger undesired side effects, and the emergence of resistant strains highlight the urgent demand for novel antifungal drug formu...
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Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM The pathogenicity of the dimorphic yeast Candida albicans is associated with filamentation, adhesion, invasion, and production of the toxin Candidalysin. However, there are certain clinical isolates and other Candida spp., that cause infection independent of filamentation or the production of...
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S9.3 Drug resistance in emerging pathogenic fungi, September 23, 2022, 4:45 PM - 6:15 PM Candida albicans is an opportunistic fungal pathogen. While nearly 40%-60% of humans are colonized harmlessly by C. albicans, prolonged use of antibiotics or an immune-compromised status can lead to mucosal or deadly systemic candidiasis (Kumamoto et al., 2020)...
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Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Microbial dysbiosis can lead to vulvovaginal candidiasis (VVC) which is characterized by a pathogenicity-induced inflammatory response progressing to neutrophil-driven immunopathology. Probiotic treatment has varied success rates and some women still experience VVC despite being colonized by...
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Intestinal microbiota dysbiosis can initiate overgrowth of commensal Candida species – a major predisposing factor for disseminated candidiasis. Commensal bacteria such as Lactobacillus rhamnosus can antagonize Candida albicans pathogenicity. Here, we investigate the interplay between C. albicans , L. rhamnosus , and intestinal epithelial cells by...
Article
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The fungal microbiota (mycobiota) is an integral part of the complex multikingdom microbial community colonizing the mammalian gastrointestinal tract and has an important role in immune regulation1–6. Although aberrant changes in the mycobiota have been linked to several diseases, including inflammatory bowel disease3–9, it is currently unknown whe...
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Pathogenic fungi kill an estimated 1.5 million people every year. Recently, we discovered that the fungal pathogen Candida albicans secretes a peptide toxin called candidalysin during mucosal infection.
Article
One billion people worldwide are affected by fungal pathogens, of which 1.6 million succumb to fungal infections per year. This review discusses the emergence and evolution of fungal pathogenesis in humans in the form of opportunistic commensal and environmental fungi. We explore the attributes that contribute to their success as pathogens and the...
Article
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Candida albicans is both a commensal and an opportunistic fungal pathogen. Invading hyphae of C. albicans secrete candidalysin, a pore-forming peptide toxin. To prevent cell death, epithelial cells must protect themselves from direct damage induced by candidalysin and by the mechanical forces exerted by expanding hyphae. We identify two key Ca²⁺-de...
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Candida albicans (C. albicans) is an opportunistic pathogen causing infections ranging from superficial to life-threatening disseminated infections. In a susceptible host, C. albicans is able to translocate through the gut barrier, promoting its dissemination into deeper organs. C. albicans hyphae can invade human epithelial cells by two well-docum...
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Candida albicans is a common commensal on human mucosal surfaces, but can become pathogenic, e.g. if the host is immunocompromised. While neutrophils, macrophages and T cells are regarded as major players in the defense against pathogenic C. albicans, the role of B cells and the protective function of their antibodies are less well characterized. I...
Article
The fungivorous amoeba Protostelium aurantium feeds on a wide range of fungal species. The image shows amoebae digesting GFP‐expressing cells of the human pathogenic yeast Candida parapsilosis. For further details, readers are referred to the article by Radosa et al. on p. e13389 of this issue.
Article
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The opportunistic pathogen Candida glabrata is the second most frequent causative agent of vulvovaginal candidiasis (VVC), a disease that affects 70–75% of women at least once during their life. However, C . glabrata is almost avirulent in mice and normally incapable of inflicting damage to vaginal epithelial cells in vitro . We thus proposed that...
Article
Candida albicans hyphae secreting the peptide toxin candidalysin (green) during invasion of epithelial cells. The toxin accumulates in the “invasion pocket” and damages the host cell. For further details, readers are referred to the article by Mogavero et al. on p. e13378 of this issue.
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Neutrophils are the most abundant leukocytes in circulation playing a key role in acute inflammation during microbial infections. Phagocytosis, one of the crucial defence mechanisms of neutrophils against pathogens, is amplified by chemotactic leukotriene (LT)B4 , which is biosynthesized via 5-lipoxygenase (5-LOX). However, extensive liberation of...
Article
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Vulvovaginal candidiasis (VVC), caused primarily by the human fungal pathogen Candida albicans , results in significant quality-of-life issues for women worldwide. Candidalysin, a toxin derived from a polypeptide (Ece1p) encoded by the ECE1 gene, plays a crucial role in driving immunopathology at the vaginal mucosa. This study aimed to determine if...
Article
Fungal airway infection (airway mycosis) is an important cause of allergic airway diseases such as asthma, but the mechanisms by which fungi trigger asthmatic reactions are poorly understood. Here, we leverage wild-type and mutant Candida albicans to determine how this common fungus elicits characteristic Th2 and Th17 cell-dependent allergic airway...
Article
Predatory interactions among microbes are a major evolutionary driving force for biodiversity. The fungivorous amoeba Protostelium aurantium has a wide fungal food spectrum including foremost pathogenic members of the genus Candida. Here we show that upon phagocytic ingestion by the amoeba, C. parapsilosis is confronted with an oxidative burst and...
Article
The human pathogenic fungus Candida albicans is a frequent cause of mucosal infections. Although the ability to transition from the yeast to the hypha morphology is essential for virulence, hypha formation and host cell invasion per se are not sufficient for the induction of epithelial damage. Rather, the hypha-associated peptide toxin, candidalysi...
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Albumin is abundant in serum but is also excreted at mucosal surfaces and enters tissues when inflammation increases vascular permeability. Host-associated opportunistic pathogens encounter albumin during commensalism and when causing infections. Considering the ubiquitous presence of albumin, we investigated its role in the pathogenesis of infecti...
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Loss or inactivation of antivirulence genes is an adaptive strategy in pathogen evolution. Candida glabrata is an important opportunistic pathogen related to baker's yeast, with the ability to both quickly increase its intrinsic high level of azole resistance and persist within phagocytes. During C. glabrata's evolution as a pathogen, the mitochond...
Article
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Candida albicans is a common opportunistic fungal pathogen that causes a wide range of infections from superficial mucosal to hematogenously disseminated candidiasis. The hyphal form plays an important role in the pathogenic process by invading epithelial cells and causing tissue damage. Notably, the secretion of the hyphal toxin candidalysin is es...
Article
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Vaginal candidiasis is an extremely common disease predominantly caused by four phylogenetically diverse species: Candida albicans; Candida glabrata; Candida parapsilosis; and Candida tropicalis. Using a time course infection model of vaginal epithelial cells and dual RNA sequencing, we show that these species exhibit distinct pathogenicity pattern...
Data
Supplementary material: -Selection of lys2 mutants of C. glabrata. -Plasmid construction. -Deoxyribonucleoside kinase (dNK) enzyme assay. -Selection of promoters for gene expression in C. glabrata. -Yeast transformants stability test.
Article
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Membrane bilayers of eukaryotic cells are an amalgam of lipids and proteins that distinguish organelles and compartmentalize cellular functions. The mammalian cell has evolved mechanisms to sense membrane tension or damage and respond as needed. In the case of the plasma membrane and phagosomal membrane these bilayers act as a barrier to microorgan...
Article
Th17 cells provide protection at barrier tissues but may also contribute to immune pathology. The relevance and induction mechanisms of pathologic Th17 responses in humans are poorly understood. Here, we identify the mucocutaneous pathobiont Candida albicans as the major direct inducer of human anti-fungal Th17 cells. Th17 cells directed against ot...
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Clearance of invading microbes requires phagocytes of the innate immune system. However, successful pathogens have evolved sophisticated strategies to evade immune killing. The opportunistic human fungal pathogen Candida albicans is efficiently phagocytosed by mac-rophages, but causes inflammasome activation, host cytolysis, and escapes after hypha...
Article
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Macrophages rely on phagosomal acidity to destroy engulfed microorganisms. To survive this hostile response, opportunistic fungi such as Candida albicans developed strategies to evade the acidic environment. C. albicans is polymorphic and able to convert from yeast to hyphae, and this transition is required to subvert the microbicidal activity of t...
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Inflammatory bowel diseases (IBD) is a multifactorial disorder. Our understanding of the role of bacteria in the pathogenesis of IBD has increased substantially; however, only scarce data exist regarding the role of commensal fungi in maintaining intestinal homeostasis and triggering IBD. Candida albicans (C. albicans) is a member of the intestinal...
Article
Bacteria use sophisticated translocation systems to manipulate or kill host cells and competing bacteria. A new study shows that bacteria also deliver anti-fungal effectors.
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Protection against microbial infection by the induction of inflammation is a key function of the IL-1 superfamily, including both classical IL-1 and the new IL-36 cytokine families. Candida albicans is a frequent human fungal pathogen causing mucosal infections. Although the initiators and effectors important in protective host responses to C. albi...
Preprint
Full-text available
Macrophages rely on phagosomal acidity to destroy engulfed microorganisms. To survive this hostile response, opportunistic fungi such as Candida albicans developed strategies to evade the acidic environment. C. albicans is polymorphic, able to convert from yeast to hyphae, and this transition is required to subvert the microbicidal activity of the...
Article
Full-text available
Life-threatening systemic infections often occur due to the translocation of pathogens across the gut barrier and into the bloodstream. While the microbial and host mechanisms permitting bacterial gut translocation are well characterized, these mechanisms are still unclear for fungal pathogens such as Candida albicans, a leading cause of nosocomial...
Article
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Nutritional immunity describes the host-driven manipulation of essential micronutrients, including iron, zinc and manganese. To withstand nutritional immunity and proliferate within their hosts, pathogenic microbes must express efficient micronutrient uptake and homeostatic systems. Here we have elucidated the pathway of cellular zinc assimilation...
Data
Zrt2 protects against calprotectin-dependent inhibition of fungal growth during C. albicans-neutrophil extracellular trap interaction. Indicated strains were incubated with wild type or S100A9-/- -derived NETs or in medium only. Following ~21 hours incubation, metabolic activity was determined by XTT assay. Activity in the presence of both NET grou...
Data
Effect of zinc and manganese, copper or iron on the growth of wild-type C. albicans and ZnT deletion mutants. Optical densities of SD overnight cultures were adjusted to 0.05 then incubated for 24 hrs in SD media containing indicated metal concentrations. Data are the mean of two independent experiments, performed in duplicate. Standard deviation (...
Data
Zrc1 is dispensable for mouse kidney colonisation. Kidney fungal burden from the mouse infection experiment reported in Fig 12. No significant differences between strains. (TIF)
Data
Fluorescent microscopy files. Original DV files used to generate Figs 7, 9 and 12. (ZIP)
Data
Phylogenetic relationship of zinc transporters in human fungal pathogens. All Zip-type proteins (PF02535) from S. cerevisiae, C. albicans, A. fumigatus, C. neoformans and C. gattii. Red circle denotes demonstrated role in pathogenicity in relevant invasive fungal infection model; blue asterisks denote no/minor role in virulence; yellow diamonds den...
Data
Zrc1 is required for virulence in a Galleria infection model. Galleria larvae (10 per group) were infected with 105 C. albicans cells and monitored every 12 h. Note that whilst wild type result in high mortality, zrc1Δ-infected larvae were not killed. Experiment performed twice—here, and in Fig 13. (TIF)
Data
Biofilm formation. Biofilms formed in RPMI (a, b), SD (c) or Spider (d) media and metabolic activity measured at 1.5 and 24 h (a, c) or biomass determined at 72 h. Experiment performed twice in triplicate. (TIF)
Data
Zrt2-dependence is bypassed at pH 7 and above. Strains from a YPD overnight culture were washed, inoculated into LZM at an OD600 of 0.005 and incubated at 30°C for seven days. (A) Growth recovery of zrt2Δ occurs at pH 7.0 and above. (B) Growth of all strains in LZM is recovered by addition of zinc (500 μM). Experiments were performed three times. *...
Data
Strains used in this study. All homozygous mutant strains created in the BWP17 (ura3::λimm434/ura3:: λimm434 his1::hisG/his1::hisG arg4::hisG/arg4::hisG) background. GFP reporters created in the CAI4 (ura3::imm434/ura3::imm434 iro1/iro1::imm434) background. Primers used in this study. FG and RG were used for deletion construct generation, pFA plasm...
Data
Relationship between environmental pH and zinc import copy number. (a) Map of soil acidity in the contiguous USA from the BONAP website (http://www.bonap.org/), reproduced with permission from Greg Schmidt, 2008, and includes data from the USDA Natural Resource Conservation Service. Pink colouring shows areas with high percentages (50–100%) of acid...
Article
Full-text available
Candida albicans is an opportunistic fungal pathogen responsible for superficial and life-threatening infections in humans. During mucosal infection, C. albicans undergoes a morphological transition from yeast to invasive filamentous hyphae that secrete candidalysin, a 31-amino-acid peptide toxin required for virulence. Candidalysin damages epithel...
Article
Full-text available
Iron availability is a central factor in infections, since iron is a critical micronutrient for all living organisms. The host employs both iron limitation and toxicity strategies to control microbial growth, and successful pathogens are able to tightly coordinate iron homeostasis in response to changing iron levels. As a commensal and opportunisti...
Data
PCR amplification of HAP43 from cDNA. 1, 16, 17, 28 - 1 kb DNA ladder; 2 - wild type; 3 - hap43Δ/Δ; 4 - hap43Δ/Δ+HAP43; 5 - ΔB-; 6 - ΔC-; 7 - ΔCys-; 8 - Δ*- ; 9 - ΔN; 10 - Δ*-A; 11 - Δ*-B; 12 - ΔA; 13 - ΔB; 14 - ΔC; 15 - ΔCys; 18, 20, 22, 24, 26 - wild type gDNA; 19, 21, 23, 25, 27 - H2O.