Hosting Infection: Experimental Models to Assay Candida Virulence

Although normally commensals in humans, Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei are capable of causing opportunistic infections in individuals with altered physiological and/or immunological responses. These fungal species are linked with a variety of infections, including oral, vaginal, gastrointestinal, and systemic infections, with C. albicans the major cause of infection. To assess the ability of different Candida species and strains to cause infection and disease requires the use of experimental infection models. This paper discusses the mucosal and systemic models of infection available to assay Candida virulence and gives examples of some of the knowledge that has been gained to date from these models

Massive induction of innate immune response to Candida albicans in the kidney in a murine intravenous challenge model

In the experimental Candida albicans intravenous challenge model, the kidney is one of the main organs involved in disease. In progressive infection, fungal burdens are found to increase over time, with rapid increases occurring from 24 h postinfection. Renal transcriptional responses were analyzed at this time in the kidneys of mice infected by either a virulent or an attenuated C. albicans strain, allowing comparison of host responses in progressive and nonprogressive infection. The results of this study demonstrate that both infections share a common transcriptional response, consisting of functions associated with the acute-phase reaction. In addition, challenge with the virulent strain led to a massively increased expression of cytokine genes, other innate response genes and genes suggestive of initiation of the adaptive immune response. This immune response to C. albicans infection, which occurs only in progressive infection, may contribute to development of sepsis and, ultimately, host death

Stress-induced nuclear accumulation is dispensable for Hog1-dependent gene expression and virulence in a fungal pathogen

The authors thank E. Veal for intellectual input. This work was funded by the UK Biotechnology and Biological Research Council [J.Q. BB/K016393/1; A.J.P.B. BB/K017365/1], the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [D.M.M. NC/N002482/1] and the Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology [097377]). D.M.M. and A.J.P.B. are also supported by the MRC Centre for Medical Mycology at the University of Aberdeen (MR/N006364/1).Peer reviewedPublisher PD

A Bright Future for Fluorescence Imaging of Fungi in Living Hosts

Funding: The PhD studentship (A.C.) was funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), grant number NC/N002482/1. We would also like to acknowledge the support of the Medical Research Council Centre for Medical Mycology at the University of Aberdeen (MR/N006364/1).Peer reviewedPublisher PD

Early-expressed chemokines predict kidney immunopathology in experimental disseminated Candida albicans infections

Available under the Creative Commons Attribution License (CCAL)Peer reviewedPublisher PD

Host responses in an ex-vivo human skin model challenged with Malassezia sympodialis

FUNDING: This project was funded by a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). We would like to acknowledge the support of Internal Funding through a Core Facilities Voucher from the University of Aberdeen. ACKNOWLEDGMENTS: The authors gratefully acknowledge the Technology hubs at the University of Aberdeen (Microscopy and Histology, qPCR facility and Proteomics) for their support, sample processing and training. Special thanks to Professor Annika Scheynius from the Karolinska Institute, Stockholm, Sweden for sharing her expertise and constructive discussions and for giving us the inspiration to work on Malassezia.Peer reviewedPublisher PD

Malassezia sympodialis Mala s 1 allergen is a potential KELCH protein that cross reacts with human skin

Open Access via the OUP Agreement We thank Giuseppe Ianiri and Joe Heitman for their continuous support and many insightful discussions. Thanks to the Microscopy and Histology Facility at the Institute of Medical Sciences, University of Aberdeen, for sample processing and access to microscopes. Thanks to Dr. David Stead and the Aberdeen Proteomics Facility, University of Aberdeen for the proteomics analysis. Funding This project was funded by a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). D.E.C.L., C.M,. and D.M. acknowledge funding from the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097 377/Z/11/Z. A.S. acknowledges, the Swedish Cancer and Allergy Fund.Peer reviewedPublisher PD

Property differences among the four major Candida albicans strain clades

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Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen

The survival of all microbes depends upon their ability to respond to environmental challenges. To establish infection, pathogens such as Candida albicans must mount effective stress responses to counter host defences while adapting to dynamic changes in nutrient status within host niches. Studies of C. albicans stress adaptation have generally been performed on glucose-grown cells, leaving the effects of alternative carbon sources upon stress resistance largely unexplored. We have shown that growth on alternative carbon sources, such as lactate, strongly influence the resistance of C. albicans to antifungal drugs, osmotic and cell wall stresses. Similar trends were observed in clinical isolates and other pathogenic Candida species. The increased stress resistance of C. albicans was not dependent on key stress (Hog1) and cell integrity (Mkc1) signalling pathways. Instead, increased stress resistance was promoted by major changes in the architecture and biophysical properties of the cell wall. Glucose- and lactate-grown cells displayed significant differences in cell wall mass, ultrastructure, elasticity and adhesion. Changes in carbon source also altered the virulence of C. albicans in models of systemic candidiasis and vaginitis, confirming the importance of alternative carbon sources within host niches during C. albicans infection

Amplification of TLO Mediator Subunit Genes Facilitate Filamentous Growth in Candida Spp

Funding: This work was funded by the National Institutes of Allergy and Infectious Disease (AI113390, LCM) and the National Institutes of General Medical Sciences (GM62483, LCM). The funders had no role in study design, data collection and analysis, decision topublish, or preparation of the manuscript.Non peer reviewedPublisher PD