Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood.

Murine infection models are widely used to study systemic candidiasis caused by . Whole-blood models can help to elucidate host-pathogens interactions and have been used for several species in human blood. We adapted the human whole-blood model to murine blood.

Experimental Evolution of Candida by Serial Passaging in Host Cells.

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 continuous culture. However, they generally provide a starting point to thorough follow-up analyses (which are specific for the organism at hand and not part of this method chapter).

Serological Proteome Analysis for the Characterization of Secreted Fungal Protein Antigens.

Defining the humoral immune response to infectious agents is important for gaining insights into infectious diseases and the response of the immune system. It can further aid development of serodiagnostic tests, discovery of vaccine antigen candidates, and immuno-epidemiological research. During the last three decades, serological proteome analyses (SERPAs) have played a significant role in characterizing the antibody response of humans or animals to fungal pathogens.

Breakthrough Fungemia in an Immuno-Compromised Adolescent: Case Report and Review of the Literature.

is a rare cause of candidemia that is known for its unique capability to rapidly acquire resistance to amphotericin B. We report the case of an adolescent with grade IV graft-vs.-host disease after hematopoietic cell transplantation who developed catheter-associated candidemia while on therapeutic doses of liposomal amphotericin B.

A TRP1-marker-based system for gene complementation, overexpression, reporter gene expression and gene modification in Candida glabrata.

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.

Phylogenomic Analysis of a 55.1-kb 19-Gene Dataset Resolves a Monophyletic that Includes the Species Complex.

Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user's needs and established successful practice. In 2013, the community voiced near unanimous support for a concept of that represented a clade comprising all agriculturally and clinically important species, including the species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus into seven genera, including the FSSC described as members of the genus , with subsequent justification in 2018 based on claims that the 2013 concept of is polyphyletic.

From bench to bedside - translational approaches in anti-fungal immunology.

Invasive fungal infections mainly occur in patients suffering from impaired immunity. Their associated mortality is high despite antifungal treatment. Thus, several efforts have been made to translate our knowledge on protective antifungal immunity into clinical application.

Human recombinant interleukin-38 suppresses inflammation in mouse models of local and systemic disease.

Interleukin (IL)-38 belongs to the IL-1 family and is part of the IL-36 subfamily due to its binding to the IL-36 Receptor (IL-1R6). In the current study, we assessed the anti-inflammatory properties of IL-38 in murine models of arthritis and systemic inflammation. First, the anti-inflammatory properties of mouse and human IL-38 precursors were compared to forms with a truncated N-terminus.

adhesion to central venous catheters: Impact of blood plasma-driven germ tube formation and pathogen-derived adhesins.

-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 yeast cells and germinated cells to naïve and human blood plasma (HBP)-coated CVC tubing. Germinated cells demonstrated up to 56.

Characterization of a Mutant Defective in All MAPKs Highlights the Major Role of Hog1 in the MAPK Signaling Network.

The success of as a pathogen relies on its ability to adapt and proliferate in different environmental niches. Pathways regulated by mitogen-activated protein kinases (MAPKs) are involved in sensing environmental conditions and developing an accurate adaptive response. Given the frequent cooperative roles of these routes in cellular functions, we have generated mutants defective in all combinations of the four described MAPKs in and characterized its phenotype regarding sensitiveness to specific drugs, morphogenesis and interaction with host immune cells.

Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans.

Invasive pulmonary aspergillosis (IPA) is a severe infection that is difficult to diagnose due to the ubiquitous presence of fungal spores, the underlying diseases of risk patients, and limitations of currently available markers. In this study, we performed a comprehensive liquid chromatography tandem mass spectrometry (LC-MS/MS)-based identification of host and fungal proteins expressed during IPA in mice and humans. The proteomic analysis of bronchoalveolar lavage samples of individual IPA and control cases allowed the description of common host factors that had significantly increased abundance in both infected animals and IPA patients compared to their controls.

Lysosome Fusion Maintains Phagosome Integrity during Fungal Infection.

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.

Reconstituting NK Cells After Allogeneic Stem Cell Transplantation Show Impaired Response to the Fungal Pathogen .

Delayed natural killer (NK) cell reconstitution after allogeneic stem cell transplantation (alloSCT) is associated with a higher risk of developing invasive aspergillosis. The interaction of NK cells with the human pathogen is mediated by the fungal recognition receptor CD56, which is relocated to the fungal interface after contact. Blocking of CD56 signaling inhibits the fungal mediated chemokine secretion of MIP-1α, MIP-1β, and RANTES and reduces cell activation, indicating a functional role of CD56 in fungal recognition.

Fungal factors involved in host immune evasion, modulation and exploitation during infection.

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 successful strategies have evolved independently among diverse fungal pathogens. These attributes are facilitated by an arsenal of fungal factors.

Clinical Vaginal Isolates and a Laboratory Strain Show Divergent Behaviors during Macrophage Interactions.

Typically, established lab strains are widely used to study host-pathogen interactions. However, to better reflect the infection process, the experimental use of clinical isolates has come more into focus. Here, we analyzed the interaction of multiple vaginal isolates of the opportunistic fungal pathogen , the most common cause of vulvovaginal candidiasis in women, with key players of the host immune system: macrophages.

The Dual Function of the Fungal Toxin Candidalysin during -Macrophage Interaction and Virulence.

The dimorphic fungus 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 of the innate immune response, infecting cells face macrophages, which mediate the clearance of invading fungi by intracellular killing.

Detection and Differentiation of Bacterial and Fungal Infection of Neutrophils from Peripheral Blood Using Raman Spectroscopy.

Neutrophils are important cells of the innate immune system and the major leukocyte subpopulation in blood. They are responsible for recognizing and neutralizing invading pathogens, such as bacteria or fungi. For this, neutrophils are well equipped with pathogen recognizing receptors, cytokines, effector molecules, and granules filled with reactive oxygen species (ROS)-producing enzymes.

The gut, the bad and the harmless: Candida albicans as a commensal and opportunistic pathogen in the intestine.

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.

Candida albicans Mrv8, is involved in epithelial damage and biofilm formation.

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.

Optofluidic detection setup for multi-parametric analysis of microbiological samples in droplets.

High-throughput microbiological experimentation using droplet microfluidics is limited due to the complexity and restricted versatility of the available detection techniques. Current detection setups are bulky, complicated, expensive, and require tedious optical alignment procedures while still mostly limited to fluorescence. In this work, we demonstrate an optofluidic detection setup for multi-parametric analyses of droplet samples by easily integrating micro-lenses and embedding optical fibers for guiding light in and out of the microfluidic chip.

Low rate of azole resistance in cases of avian aspergillosis in Germany.

Aspergillosis is the most common fungal disease of the avian respiratory tract. Due to delayed diagnosis and treatment failure, the outcome of these infections is often poor. We investigate 159 cases of avian aspergillosis among captive birds in Germany to define clinical features as well as the frequency of in vitro triazole resistance.

Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in Candida albicans.

The capacity of to reversibly change its morphology between yeast and filamentous stages is crucial for its virulence. Formation of hyphae correlates with the upregulation of genes and , which are involved in pathogenicity processes such as invasion, iron acquisition, and host cell damage. The global repressor Tup1 and its cofactor Nrg1 are considered to be the main antagonists of hyphal development in However, our experiments revealed that Tup1, but not Nrg1, was required for full expression of and In contrast to , overexpression of was found to inhibit neither filamentous growth nor transcription of and In addition, we identified the transcription factor Ahr1 as being required for full expression of both genes.

Interference with ERK-dimerization at the nucleocytosolic interface targets pathological ERK1/2 signaling without cardiotoxic side-effects.

Dysregulation of extracellular signal-regulated kinases (ERK1/2) is linked to several diseases including heart failure, genetic syndromes and cancer. Inhibition of ERK1/2, however, can cause severe cardiac side-effects, precluding its wide therapeutic application. ERK-autophosphorylation was identified to cause pathological cardiac hypertrophy.

Fungal biotin homeostasis is essential for immune evasion after macrophage phagocytosis and virulence.

Biotin is an important cofactor for multiple enzymes in central metabolic processes. While many bacteria and most fungi are able to synthesise biotin de novo, Candida spp. are auxotrophic for this vitamin and thus require efficient uptake systems to facilitate biotin acquisition during infection.

Cooperative Role of MAPK Pathways in the Interaction of with the Host Epithelium.

is an important human fungal pathogen responsible for tens of millions of infections as well as hundreds of thousands of severe life-threatening infections each year. MAP kinase (MAPK) signal transduction pathways facilitate the sensing and adaptation to external stimuli and control the expression of key virulence factors such as the yeast-to-hypha transition, the biogenesis of the cell wall, and the interaction with the host. In the present study, we have combined molecular approaches and infection biology to analyse the role of MAPK pathways during an epithelial invasion.