Distinct roles for different autophagy-associated genes in the virulence of the fungal wheat pathogen Zymoseptoria tritici.

The fungal wheat pathogen Zymoseptoria tritici causes major crop losses as the causal agent of the disease Septoria tritici blotch. The infection cycle of Z. tritici displays two distinct phases, beginning with an extended symptomless phase of 1-2 weeks, before the fungus induces host cell death and tissue collapse in the leaf.

Differences in fungal immune recognition by monocytes and macrophages: -mannan can be a shield or activator of immune recognition.

We designed experiments to assess whether fungal cell wall mannans function as an immune shield or an immune agonist. Fungal cell wall β-(1,3)-glucan normally plays a major and dominant role in immune activation. The outer mannan layer has been variously described as an immune shield, because it has the potential to mask the underlying β-(1,3)-glucan, or an immune activator, as it also has the potential to engage with a wide range of mannose detecting PRRs.

Functional Characterization of a Novel Oxidative Stress Protection Protein in the Pathogenic Yeast .

Candida species are important pathogens of humans and the fourth most commonly isolated pathogen from nosocomial blood stream infections. Although Candida albicans is the principle causative agent of invasive candidosis, the incidence of infections has rapidly grown. The reason for this increase is not fully understood, but it is clear that the species has a higher innate tolerance to commonly administered azole antifungals, in addition to being highly tolerant to stresses especially oxidative stress.

Attenuating the emergence of anti-fungal drug resistance by harnessing synthetic lethal interactions in a model organism.

Drug resistance is a rapidly emerging concern, thus prompting the development of novel therapeutics or combinatorial therapy. Currently, combinatorial therapy targets are based on knowledge of drug mode of action and/or resistance mechanisms, constraining the number of target proteins. Unbiased genome-wide screens could reveal novel genetic components within interaction networks as potential targets in combination therapies.

The ORFeome: A Functional Genomics Community Resource.

Libraries of protein-encoding sequences can be generated by identification of open reading frames (ORFs) from a genome of choice that are then assembled into collections of plasmids termed ORFeome libraries. These represent powerful resources to facilitate functional genomic characterization of genes and their encoded products. Here, we report the generation of an ORFeome for , which causes the most serious disease of wheat in temperate regions of the world.

The MNN2 Gene Knockout Modulates the Antifungal Resistance of Biofilms of Candida glabrata.

biofilms are recognized to have high resistance to antifungals. In order to understand the effect of mannans in the resistance profile of mature biofilms, Δ was evaluated. Biofilm cell walls were analysed by confocal laser scanning microscopy (CLSM) and their susceptibility was assessed for fluconazole, amphotericin B, caspofungin, and micafungin.

Author Correction: Drug-mediated metabolic tipping between antibiotic resistant states in a mixed-species community.

In the version of this Article originally published, the following sentence was missing from the Acknowledgements: "R.E.B.

Drug-mediated metabolic tipping between antibiotic resistant states in a mixed-species community.

Microbes rarely exist in isolation, rather, they form intricate multi-species communities that colonize our bodies and inserted medical devices. However, the efficacy of antimicrobials is measured in clinical laboratories exclusively using microbial monocultures. Here, to determine how multi-species interactions mediate selection for resistance during antibiotic treatment, particularly following drug withdrawal, we study a laboratory community consisting of two microbial pathogens.

A Host-Pathogen Interaction Screen Identifies as a Mediator of Defenses Against Reactive Oxygen Species.

() forms part of the normal human gut microbiota but can cause life-threatening invasive infections in immune-compromised individuals. displays high resistance to common azole antifungals, which necessitates new treatments. In this investigation, we identified five deletion mutants (, , hir3, and ) from a library of 196 transcription factor mutants that were unable to grow and activate an immune response in larvae.

New and Improved Techniques for the Study of Pathogenic Fungi.

Fungal pathogens pose serious threats to human, plant, and ecosystem health. Improved diagnostics and antifungal strategies are therefore urgently required. Here, we review recent developments in online bioinformatic tools and associated interactive data archives, which enable sophisticated comparative genomics and functional analysis of fungal pathogens in silico.

Utilising established SDL-screening methods as a tool for the functional genomic characterisation of model and non-model organisms.

The trend for large-scale genetic and phenotypic screens has revealed a wealth of information on biological systems. A major challenge is understanding how genes function and putative roles in networks. The majority of current gene knowledge is garnered from studies utilising the model yeast Saccharomyces cerevisiae.

Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans.

The major fungal pathogen of humans, Candida albicans, mounts robust responses to oxidative stress that are critical for its virulence. These responses counteract the reactive oxygen species (ROS) that are generated by host immune cells in an attempt to kill the invading fungus. Knowledge of the dynamical processes that instigate C.

Candida glabrata: new tools and technologies-expanding the toolkit.

In recent years, there has been a noticeable rise in fungal infections related to non-albicans Candida species, including Candida glabrata which has both intrinsic resistance to and commonly acquired resistance to azole antifungals. Phylogenetically, C. glabrata is more closely related to the mostly non-pathogenic model organism Saccharomyces cerevisiae than to other Candida species.

Conditional gene expression and promoter replacement in Zymoseptoria tritici using fungal nitrate reductase promoters.

Studying essential genes in haploid fungi requires specific tools. Conditional promoter replacement (CPR) is an efficient method for testing gene essentiality. However, this tool requires promoters that can be strongly down-regulated.

Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans.

Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CTG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C.

Mechanisms underlying the exquisite sensitivity of Candida albicans to combinatorial cationic and oxidative stress that enhances the potent fungicidal activity of phagocytes.

Immune cells exploit reactive oxygen species (ROS) and cationic fluxes to kill microbial pathogens, such as the fungus Candida albicans. Yet, C. albicans is resistant to these stresses in vitro.

Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes.

The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat.

Identification of Candida glabrata genes involved in pH modulation and modification of the phagosomal environment in macrophages.

Candida glabrata currently ranks as the second most frequent cause of invasive candidiasis. Our previous work has shown that C. glabrata is adapted to intracellular survival in macrophages and replicates within non-acidified late endosomal-stage phagosomes.

The form of a trade-off determines the response to competition.

Understanding how populations and communities respond to competition is a central concern of ecology. A seminal theoretical solution first formalised by Levins (and re-derived in multiple fields) showed that, in theory, the form of a trade-off should determine the outcome of competition. While this has become a central postulate in ecology it has evaded experimental verification, not least because of substantial technical obstacles.

Differential virulence of Candida glabrata glycosylation mutants.

The fungus Candida glabrata is an important and increasingly common pathogen of humans, particularly in immunocompromised hosts. Despite this, little is known about the attributes that allow this organism to cause disease or its interaction with the host immune system. However, in common with other fungi, the cell wall of C.

Modelling the activation of alkaline pH response transcription factor PacC in Aspergillus nidulans: involvement of a negative feedback loop.

Alkaline pH adaptation represents an important environmental stress response in Aspergillus nidulans. It is mediated by the pal signalling pathway and the PacC transcription factor. Although studied extensively experimentally, the activation mechanism of PacC has not been quantified, and it is not clear how this activation is regulated.

An integrative model of ion regulation in yeast.

Yeast cells are able to tolerate and adapt to a variety of environmental stresses. An essential aspect of stress adaptation is the regulation of monovalent ion concentrations. Ion regulation determines many fundamental physiological parameters, such as cell volume, membrane potential, and intracellular pH.

A systems biology analysis of long and short-term memories of osmotic stress adaptation in fungi.

Background: Saccharomyces cerevisiae senses hyperosmotic conditions via the HOG signaling network that activates the stress-activated protein kinase, Hog1, and modulates metabolic fluxes and gene expression to generate appropriate adaptive responses. The integral control mechanism by which Hog1 modulates glycerol production remains uncharacterized. An additional Hog1-independent mechanism retains intracellular glycerol for adaptation.