Dissection of the Candida albicans class I chitin synthase promoters

We acknowledge financial support from the Biotechnology and Biological Sciences Research Council (10161), Medical Research Council (New Investigator Award to C.A.M.), the European Community FUNGALWALL and SIGNALPATH initiatives and the Wellcome Trust.Peer reviewedPublisher PD

Cell wall stress induces alternative fungal cytokinesis and septation strategies

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Cell wall protection by the Candida albicans class I chitin synthases

Open Access funded by Medical Research Council Acknowledgments We thank Kevin Mackenzie in the Microscopy and Histology Core Facility (Institute of Medical Sciences, University of Aberdeen), and Donna MacCallum for helpful statistical advice. This work was supported by grants from the Wellcome Trust (0868827 and 080088) including a Wellcome Trust Strategic Award (097377) and an Investigator Award to NG (101873), an MRC New Investigator Award to ML (MR/J008230/1) and a PhD scholarship awarded to KP from the Ministry of Sciences and Technology and Chiang Mai University, Thailand. Author contributions are as follows: KP constructed strains, performed the majority of the experiments, analyzed the data and contributed to the preparation of the manuscript. JA produced Fig. S1 using the data from the phosphoproteomic analysis conducted by SP and AB. NG conceived and designed experiments, analyzed data and commented on drafts of the manuscript. ML constructed strains, conceived, designed and performed experiments, analyzed data and wrote the manuscript.Peer reviewedPublisher PD

Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation

Funding: JW and NARG thank the Wellcome Trust (080088, 086827, 075470), The Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377) and the European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) for funding. MGN was supported by a Vici grant of the Netherlands Organisation for Scientific Research. AJPB and DMM were funded by STRIFE, ERC-2009-AdG-249793 and AJPB additionally by FINSysB, PITN-GA-2008-214004 and the BBSRC [BB/F00513X/1]. MDL was supported by the MRC (MR/J008230/1). GDB and SV were funded by the Wellcome Trust (086558) and TB and MK were funded by the Deutsche Forschungsgemeinschaft (Bi 696/3-1; Bi 696/5-2; Bi 696/10-1). MS was supported by the Deutsche Forschungsgemeinschaft (Sch 897/1-3) and the National Institute of Dental and Craniofacial Research (R01 DE017514-01). TDK and RKSM were funded by the National Institute of Health (AR056296, AI101935) and the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Crosstalk between the calcineurin and cell wall integrity pathways prevents chitin overexpression in Candida albicans

Funding Information: We thank Carol Munro for helpful discussions during the research, Raif Yuecel, Elizabeth Adams, Linda Duncan, Barry Lewis and Kimberley Sim for assistance with FACS at Aberdeen Cytometry Core Facility, and Yang Meng and Dominique Sanglard with help in construction of mutants. We also thank Linghuo Jiang, David Soll, Jes?s Pla, Jan Quinn, Terry Roemer and Joseph Heitman for mutant strains. N.A.R.G. acknowledges support from the Wellcome Trust [Senior Investigator (101873/Z/13/Z), Collaborative (200208/A/15/Z and 215599/Z/19/Z) and Strategic (097377/Z11/Z) Awards] and from the Medical Research Council Centre for Medical Mycology (MR/N006364/2). This work was also supported by a Marie Curie FP7-PEOPLE-ITN-2008 grant (MB004 RGE0655 ARIADNE) and by a Wellcome Trust project grant (086827). Open access funding provided by University of Exeter. Deposited in PMC for immediate release.Peer reviewedPublisher PD

The Viscoelastic Properties of the Fungal Cell Wall Allow Traffic of AmBisome as Intact Liposome Vesicles

NARG thanks The Wellcome Trust (080088, 086827, 075470, 099215 & 097377) and MRC Centre for Medical Mycology (MR/N006364/1) and acknowledges financial support from Gilead Sciences for a studentship and grant IX-EU-131-0262. Dr. Linda Soo Hoo and Tark Bunch of Gilead provided expert technical assistance in liposomal sample preparations and GF provided gold labelled test articles. JAM is funded in part from a research grant from Gilead Sciences Inc. ML was supported by the MRC (MR/J008230/1). AC was supported in part by 5R01HL059842, 5R01AI033774, 5R37AI033142, and 5R01AI052733. We thank Debbie Wilkinson and Kevin McKenzie at the Imaging Core Facility at the University of Aberdeen for expert assistance with TEM.Peer reviewedPublisher PD

Recognition and blocking of innate immunity cells by Candida albicans chitin

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Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition

Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection

The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans

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The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD