Bernhard Hube

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

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...

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...

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...

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...

For the human fungal pathogen Candida albicans , metabolic flexibility and the ability to transition between yeast and filamentous growth states are key virulence traits that enable disease in the host. These traits are particularly important during the interaction of C. albicans with macrophages, where the fungus must utilize multiple alternative...

Human fungal pathogens are a deadly and underappreciated risk to global health that most severely affect immunocompromised individuals. A virulence attribute shared by some of the most clinically relevant fungal species is their ability to survive inside macrophages and escape from these immune cells. In this review, we discuss the mechanisms behin...

The peptide toxin candidalysin, secreted by Candida albicans hyphae, promotes stimulation of neutrophil extracellular traps (NETs). However, candidalysin alone triggers a distinct mechanism for NET‐like structures (NLS), which are more compact and less fibrous than canonical NETs. Candidalysin activates NADPH oxidase and calcium influx, with both p...

Aberrant CD4⁺ T cell reactivity against intestinal microorganisms is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microorganism-specific, pathogenic T cell phenotypes remain largely unknown. In the present study, we identified common gut commensal and food-deri...

Candida species overgrowth in the human gut is considered a prerequisite for invasive candidiasis, but our understanding of gut bacteria promoting or restricting this overgrowth is still limited. By integrating cross-sectional mycobiome and shotgun metagenomics data from the stool of 75 male and female cancer patients at risk but without systemic c...

The human immune system uses an arsenal of effector mechanisms to prevent and counteract infections. Yet, some fungal species are extremely successful as human pathogens, which can be attributed to a wide variety of strategies by which these fungi evade, exploit, and modulate the immune system. These fungal pathogens normally are either harmless co...

Background: The fungus Aspergillus fumigatus causes a variety of clinical phenotypes in patients with cystic fibrosis (pwCF). T-helper (Th) cells orchestrate immune responses against fungi, but the types of A. fumigatus-specific Th-cells in pwCF and their contribution to protective immunity or inflammation remain poorly characterized. Methods: W...

Investigating the ecological context of microbial predator-prey interactions enables the identification of microorganisms, which produce multiple secondary metabolites to evade predation or to kill the predator. In addition, genome mining combined with molecular biology methods can be used to identify further biosynthetic gene clusters that yield n...

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...

Candida albicans produces an important virulence factor, the hypha-associated Ece1-derived secreted peptide toxin candidalysin, which is crucial for the establishment of mucosal and systemic infections. C. albicans has also long been known to be hemolytic, yet the hemolytic factor has not been clearly identified. Here, we show that candidalysin is...

Candida 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 val...

Sample degradation, in particular of biomolecules, frequently occurs in surface-enhanced Raman spectroscopy (SERS) utilizing supported silver SERS substrates. Currently, thermal and/or photocatalytic effects are considered to cause sample degradation. This paper establishes the efficient inhibition of sample degradation using iodide which is demons...

The cytolytic peptide toxin candidalysin is secreted by the invasive, hyphal form of the human fungal pathogen, Candida albicans . Candidalysin is essential for inducing host cell damage during mucosal and systemic C. albicans infections, resulting in neutrophil recruitment. Neutrophil influx to C. albicans -infected tissue is critical for limiting...

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...

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...

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)...

S4.3 Emergent species of the Candida genus, September 22, 2022, 10:30 AM - 12:00 PM Candida glabrata is among the most common pathogenic yeasts of humans. Yet, this fungus is phylogenetically, genetically, and phenotypically very different from other clinically relevant Candida species. This includes an unusual high level of intrinsic resistance to...

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...

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...

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...

Chitin is a highly abundant polysaccharide in nature and linked to immune recognition of fungal infections and asthma in humans. Ubiquitous in fungi and insects, chitin is absent in mammals and plants and, thus, represents a microbe-associated molecular pattern (MAMP). However, the highly polymeric chitin is insoluble, which potentially hampers rec...

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...

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.

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...

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...

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...

Introduction The FunHoMic project is a Marie Skłodowska-Curie Innovative Training Network comprising 13 PhD students, 8 academic partners and 3 industry partnersaimingto understand the interplay between fungi, hostsand microbiota to improve prevention and treatment of fungal infections. Importance About 2 billion people suffer fungal infections, w...

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.

Candida albicans is usually a benign member of the human gut microbiota, but can become pathogenic under certain circumstances, for example in an immunocompromised host. The innate immune system, in particular neutrophils and macrophages, constitutes a crucial first line of defense against fungal invasion, however adaptive immunity may provide long...

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...

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.

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...

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...

The burden of fungal infections for humans, animals and plants is widely underestimated and comprises deadly infections as well as great conomic costs. Despite that, antifungal drugs are scarce and emergence of resistance in fungal strains contributes to a high mortality. To overcome this shortage, we propose toxic intermediates and their controlli...

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...

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...

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...

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...

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...

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...

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...

The pathogenesis of life-threatening infections caused by emerging fungal pathogens remains largely unexplored. A new study provides unprecedented evidence for the pivotal role of a new ricin-like protein toxin, named mucoricin, in causing organ necrosis and mortality in Mucorales infections.

Fungal infections (mycoses) affect over a billion people per year. Approximately two million of these infections are life-threatening, especially for patients with a compromised immune system. Fungi of the genera Aspergillus, Candida, Histoplasma, and Cryptococcus are opportunistic pathogens that contribute to a substantial number of mycoses. To op...

Many fungi can cause deadly diseases in humans, and nearly every human will suffer from some kind of fungal infection in their lives. Only few antifungals are available, and some of these fail to treat intrinsically resistant species and the ever-increasing number of fungal strains that have acquired resistance. In nature, bacteria and fungi displa...

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 mitochon...

Experimental evolution is an experiment class of its own; instead of requiring an a priori hypothesis, the genetic adaptation of microbes to defined environments tells us about the underlying pathways and mechanisms. Such experiments are often deceptively simple in their design, based on a single abiotic stressor and what is in essence a long-term...

Microbial interactions with epithelial barriers are important steps preceding disease. Infections with Candida albicans are no exception. This opportunistic fungus, commonly harmlessly residing in close proximity to human epithelia, can shift to a more pathogenic form, can invade tissues, and cause disease. Pathogenesis, in C. albicans as well as i...

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 predic...

Although less prevalent than its relative Candida albicans, the yeast Candida glabrata is a successful pathogen of humans which causes life-threatening candidiasis. It is thus vital to understand the pathogenicity mechanisms and contributing genes in C. glabrata. However, gene complementation as a tool for restoring the function of a previously del...

Candida albicans-related bloodstream infections are often associated with infected central venous catheters (CVC) triggered by microbial adhesion and biofilm formation. We utilized single-cell force spectroscopy (SCFS) and flow chamber models to investigate the adhesion behavior of C. albicans yeast cells and germinated cells to naïve and human blo...

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 ca...

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 basi...

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...

Human and plant pathogenic fungi have a major impact on public health and agriculture. Although these fungi infect very diverse hosts and are often highly adapted to specific host niches, they share surprisingly similar mechanisms that mediate immune evasion, modulation of distinct host targets, and exploitation of host nutrients, highlighting that...

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 funga...

Candida albicans is a regular member of the intestinal microbiota in the majority of the human population. This underscores C. albicans’ adaptation to life in the intestine without inducing competitive interactions with other microbes, or immune responses detrimental to its survival. However, specific conditions such as a dysbalanced microbiome, a...

The dimorphic fungus Candida albicans is both a harmless commensal organism on mucosal surfaces and an opportunistic pathogen. Under certain predisposing conditions, the fungus can overgrow the mucosal microbiome and cause both superficial and life-threatening systemic infections after gaining access to the bloodstream. As the first line of defense...

Candida albicans is the most common human fungal pathogen that can cause superficial and deep-seated infections in susceptible individuals. Despite its medical importance, the vast majority of C. albicans genes remain of unknown function. Here we report a role for the lineage-specific gene, MRV8, in host pathogen interactions, mycelial microcolony...

Candida albicans is a major human fungal pathogen and the leading cause of systemic Candida infections. In recent years, Als3 and Ece1 were identified as important factors for fungal virulence. Transcription of both corresponding genes is closely associated with hyphal growth. Here, we describe how Tup1, normally a global repressor of gene expressi...

Host released alarmins and antimicrobial peptides (AMPs) are highly effective as antifungal agents and inducers. Whilst some are expressed constitutively at mucosal tissues, the primary site of many infections, others are elicited in response to pathogens. In the context of Candida albicans, the fungal factors inducing the release of these innate i...

Biotin is an important cofactor for multiple enzymes in central metabolic processes. While many bacteria and most fungi are able to synthesize biotin de novo, Candida spp. are auxotrophic for this vitamin and thus require efficient uptake systems to facilitate biotin acquisition during infection. Here we show that C. glabrata and C. albicans use a...