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2. Immune cells fold and damage fungal hyphae

Author

Bain, Judith M., Alonso, M. Fernanda, Childers, Delma S., Walls, Catriona A., Mackenzie, Kevin, Pradhan, Arnab, Lewis, Leanne E., Louw, Johanna, Avelar, Gabriela M., Larcombe, Daniel E., Netea, Mihai G., Gow, Neil A. R., Brown, Gordon D., Erwig, Lars P., and Brown, Alistair J. P.

Published
2021

5. A CO 2 sensing module modulates β-1,3-glucan exposure in Candida albicans

Author

Avelar, Gabriela M., primary, Pradhan, Arnab, additional, Ma, Qinxi, additional, Hickey, Emer, additional, Leaves, Ian, additional, Liddle, Corin, additional, Rodriguez Rondon, Alejandra V., additional, Kaune, Ann-Kristin, additional, Shaw, Sophie, additional, Maufrais, Corinne, additional, Sertour, Natacha, additional, Bain, Judith M., additional, Larcombe, Daniel E., additional, de Assis, Leandro J., additional, Netea, Mihai G., additional, Munro, Carol A., additional, Childers, Delma S., additional, Erwig, Lars P., additional, Brown, Gordon D., additional, Gow, Neil A. R., additional, Bougnoux, Marie-Elisabeth, additional, d'Enfert, Christophe, additional, and Brown, Alistair J. P., additional

Published
2024
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6. Impact of the Environment upon the Candida albicans Cell Wall and Resultant Effects upon Immune Surveillance

Author

Childers, Delma S., Avelar, Gabriela M., Bain, Judith M., Larcombe, Daniel E., Pradhan, Arnab, Budge, Susan, Heaney, Helen, Brown, Alistair J. P., Ahmed, Rafi, Series Editor, Akira, Shizuo, Series Editor, Aktories, Klaus, Series Editor, Casadevall, Arturo, Series Editor, Compans, Richard W, Series Editor, Galan, Jorge E, Series Editor, Garcia-Sastre, Adolfo, Series Editor, Malissen, Bernard, Series Editor, Rappuoli, Rino, Series Editor, and Latgé, Jean-Paul, editor

Published
2020
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8. Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris

Author

Bruno, Mariolina, Kersten, Simone, Bain, Judith M., Jaeger, Martin, Rosati, Diletta, Kruppa, Michael D., Lowman, Douglas W., Rice, Peter J., Graves, Bridget, Ma, Zuchao, Jiao, Yue Ning, Chowdhary, Anuradha, Renieris, George, van de Veerdonk, Frank L., Kullberg, Bart-Jan, Giamarellos-Bourboulis, Evangelos J., Hoischen, Alexander, Gow, Neil A. R., Brown, Alistair J. P., Meis, Jacques F., Williams, David L., and Netea, Mihai G.

Published
2020
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10. Candida auris undergoes adhesin-dependent and -independent cellular aggregation.

Author

Pelletier, Chloe, Shaw, Sophie, Alsayegh, Sakinah, Brown, Alistair J. P., and Lorenz, Alexander

Subjects
CANDIDA, LIFE cycles (Biology), CELL aggregation, CELL separation, NOSOCOMIAL infections
Abstract

Candida auris is a fungal pathogen of humans responsible for nosocomial infections with high mortality rates. High levels of resistance to antifungal drugs and environmental persistence mean these infections are difficult to treat and eradicate from a healthcare setting. Understanding the life cycle and the genetics of this fungus underpinning clinically relevant traits, such as antifungal resistance and virulence, is of the utmost importance to develop novel treatments and therapies. Epidemiological and genomic studies have identified five geographical clades (I-V), which display phenotypic and genomic differences. Aggregation of cells, a phenotype primarily of clade III strains, has been linked to reduced virulence in some infection models. The aggregation phenotype has thus been associated with conferring an advantage for (skin) colonisation rather than for systemic infection. However, strains with different clade affiliations were compared to infer the effects of different morphologies on virulence. This makes it difficult to distinguish morphology-dependent causes from clade-specific or even strain-specific genetic factors. Here, we identify two different types of aggregation: one induced by antifungal treatment which is a result of a cell separation defect; and a second which is controlled by growth conditions and only occurs in strains with the ability to aggregate. The latter aggregation type depends on an ALS-family adhesin which is differentially expressed during aggregation in an aggregative C. auris strain. Finally, we demonstrate that macrophages cannot clear aggregates, suggesting that aggregation might after all provide a benefit during systemic infection and could facilitate long-term persistence in the host. Author summary: Candida auris is a single-celled fungus, a yeast, that can cause severe infections in hospital patients. This fungus is difficult to treat because it is resistant to many antifungal drugs. Therefore, to understand the processes that enhance the virulence of this yeast with a view to developing new treatments is of the utmost importance. Previous studies have found that C. auris can form aggregates, or clumps of cells, which may play a role in how the fungus infects people. In this study, we identified two different types of aggregation in C. auris, one triggered by antifungal treatment, and another controlled by growth conditions. This discovery allowed us to study aggregate formation in the same genetic background. In doing so, we found that a certain protein, an ALS-family adhesin, is involved in the aggregation process. Surprisingly, we also discovered that aggregates may promote infection by making it harder for the immune system to clear the yeast. This new understanding could help researchers develop better ways to fight C. auris infections. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Glucose-enhanced oxidative stress resistance—A protective anticipatory response that enhances the fitness of Candida albicans during systemic infection

Author

Larcombe, Daniel E., primary, Bohovych, Iryna M., additional, Pradhan, Arnab, additional, Ma, Qinxi, additional, Hickey, Emer, additional, Leaves, Ian, additional, Cameron, Gary, additional, Avelar, Gabriela M., additional, de Assis, Leandro J., additional, Childers, Delma S., additional, Bain, Judith M., additional, Lagree, Katherine, additional, Mitchell, Aaron P., additional, Netea, Mihai G., additional, Erwig, Lars P., additional, Gow, Neil A. R., additional, and Brown, Alistair J. P., additional

Published
2023
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15. The pathobiology of human fungal infections

Author

Brown, Gordon D., Ballou, Elizabeth R., Bates, Steven, Bignell, Elaine M., Borman, Andrew M., Brand, Alexandra C., Brown, Alistair J. P., Coelho, Carolina, Cook, Peter C., Farrer, Rhys A., Govender, Nelesh P., Gow, Neil A. R., Hope, William, Hoving, J. Claire, Dangarembizi, Rachael, Harrison, Thomas S., Johnson, Elizabeth M., Mukaremera, Liliane, Ramsdale, Mark, Thornton, Christopher R., Usher, Jane, Warris, Adilia, and Wilson, Duncan

Abstract

Human fungal infections are a historically neglected area of disease research, yet they cause more than 1.5 million deaths every year. Our understanding of the pathophysiology of these infections has increased considerably over the past decade, through major insights into both the host and pathogen factors that contribute to the phenotype and severity of these diseases. Recent studies are revealing multiple mechanisms by which fungi modify and manipulate the host, escape immune surveillance and generate complex comorbidities. Although the emergence of fungal strains that are less susceptible to antifungal drugs or that rapidly evolve drug resistance is posing new threats, greater understanding of immune mechanisms and host susceptibility factors is beginning to offer novel immunotherapeutic options for the future. In this Review, we provide a broad and comprehensive overview of the pathobiology of human fungal infections, focusing specifically on pathogens that can cause invasive life-threatening infections, highlighting recent discoveries from the pathogen, host and clinical perspectives. We conclude by discussing key future challenges including antifungal drug resistance, the emergence of new pathogens and new developments in modern medicine that are promoting susceptibility to infection.

Published
2024
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21. Nature of β-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation

Author

de Assis, Leandro José, primary, Bain, Judith M., additional, Liddle, Corin, additional, Leaves, Ian, additional, Hacker, Christian, additional, Peres da Silva, Roberta, additional, Yuecel, Raif, additional, Bebes, Attila, additional, Stead, David, additional, Childers, Delma S., additional, Pradhan, Arnab, additional, Mackenzie, Kevin, additional, Lagree, Katherine, additional, Larcombe, Daniel E., additional, Ma, Qinxi, additional, Avelar, Gabriela Mol, additional, Netea, Mihai G., additional, Erwig, Lars P., additional, Mitchell, Aaron P., additional, Brown, Gordon D., additional, Gow, Neil A. R., additional, and Brown, Alistair J. P., additional

Published
2022
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24. Translational Control of GCN4

Author

You, Tao, Coghill, George M., Brown, Alistair J. P., Dubitzky, Werner, editor, Wolkenhauer, Olaf, editor, Cho, Kwang-Hyun, editor, and Yokota, Hiroki, editor

Published
2013
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25. S9.4c Diverse environmental inputs mediate changes in β-glucan exposure at the Candida albicans cell surface thereby influencing tissue colonisation during systemic infection

Author

Pradhan, Arnab, primary, Ma, Qinxi, additional, Hickey, Emer, additional, Avelar, Gabriela, additional, Larcombe, Daniel, additional, Bain, Judith, additional, Childers, Delma, additional, Dambuza, Ivy, additional, Leaves, Ian, additional, de Assis, Leandro Jose, additional, Netea, Mihai, additional, Brown, Gordon, additional, Erwig, Lars, additional, Gow, Neil A. R., additional, and Brown, Alistair J. P., additional

Published
2022
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29. Stress Adaptation

Author

Brown, Alistair J. P., primary, Cowen, Leah E., additional, di Pietro, Antonio, additional, and Quinn, Janet, additional

Published
2017
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33. Fungal resilience and host–pathogen interactions: Future perspectives and opportunities.

Author

Brown, Alistair J. P.

Subjects
*CLONE cells, *DRUG tolerance, *PHENOTYPIC plasticity, *DRUG resistance
Abstract

We are constantly exposed to the threat of fungal infection. The outcome—clearance, commensalism or infection—depends largely on the ability of our innate immune defences to clear infecting fungal cells versus the success of the fungus in mounting compensatory adaptive responses. As each seeks to gain advantage during these skirmishes, the interactions between host and fungal pathogen are complex and dynamic. Nevertheless, simply compromising the physiological robustness of fungal pathogens reduces their ability to evade antifungal immunity, their virulence, and their tolerance against antifungal therapy. In this article I argue that this physiological robustness is based on a 'Resilience Network' which mechanistically links and controls fungal growth, metabolism, stress resistance and drug tolerance. The elasticity of this network probably underlies the phenotypic variability of fungal isolates and the heterogeneity of individual cells within clonal populations. Consequently, I suggest that the definition of the fungal Resilience Network represents an important goal for the future which offers the clear potential to reveal drug targets that compromise drug tolerance and synergise with current antifungal therapies. [ABSTRACT FROM AUTHOR]

Published
2023
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34. Erg25 Controls Host-Cholesterol Uptake Mediated by Aus1p-Associated Sterol-Rich Membrane Domains in Candida glabrata

Author

Okamoto, Michiyo, primary, Takahashi-Nakaguchi, Azusa, additional, Tejima, Kengo, additional, Sasamoto, Kaname, additional, Yamaguchi, Masashi, additional, Aoyama, Toshihiro, additional, Nagi, Minoru, additional, Tanabe, Kohichi, additional, Miyazaki, Yoshitsugu, additional, Nakayama, Hironobu, additional, Sasakawa, Chihiro, additional, Kajiwara, Susumu, additional, Brown, Alistair J. P., additional, Teixeira, Miguel C., additional, and Chibana, Hiroji, additional

Published
2022
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37. Immune Recognition of Candida albicans β-Glucan by Dectin-1

Author

Gow, Neil A. R., Netea, Mihai G., Munro, Carol A., Ferwerda, Gerben, Bates, Steven, Mora-Montes, Héctor M., Walker, Louise, Jansen, Trees, Jacobs, Liesbeth, Tsoni, Vicky, Brown, Gordon D., Odds, Frank C., Van der Meer, Jos W. M., Brown, Alistair J. P., and Kullberg, Bart Jan

Published
2007
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40. Human gut bifidobacteria inhibit the growth of the opportunistic fungal pathogen Candida albicans.

Author

Ricci, Liviana, Mackie, Joanna, Donachie, Gillian E, Chapuis, Ambre, Mezerová, Kristýna, Lenardon, Megan D, Brown, Alistair J P, Duncan, Sylvia H, and Walker, Alan W

Subjects
CANDIDA albicans, BIFIDOBACTERIUM, FUNGAL growth, SHORT-chain fatty acids, HUMAN microbiota, GUT microbiome
Abstract

The human gut microbiota protects the host from invading pathogens and the overgrowth of indigenous opportunistic species via a process called colonization resistance. Here, we investigated the antagonistic activity of human gut bacteria towards Candida albicans , an opportunistic fungal pathogen that can cause severe infections in susceptible individuals. Coculture batch incubations of C. albicans in the presence of faecal microbiota from six healthy individuals revealed varying levels of inhibitory activity against C. albicans. 16S rRNA gene amplicon profiling of these faecal coculture bacterial communities showed that the Bifidobacteriaceae family, and Bifidobacterium adolescentis in particular, were most correlated with antagonistic activity against C. albicans. Follow-up mechanistic studies performed under anaerobic conditions confirmed that culture supernatants of Bifidobacterium species, particularly B. adolescentis , inhibited C. albicans in vitro. Fermentation acids (FA), including acetate and lactate, present in the bifidobacterial supernatants were important contributors to inhibitory activity. However, increasing the pH of both bacterial supernatants and mixtures of FA reduced their anti- Candida effects, indicating a combinatorial effect of prevailing pH and FA. This work, therefore, demonstrates potential mechanisms underpinning gut microbiome-mediated colonization resistance against C. albicans , and identifies particularly inhibitory components such as bifidobacteria and FA as targets for further study. [ABSTRACT FROM AUTHOR]

Published
2022
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41. Additional file 1 of Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata

Author

Chew, Shu Yih, Brown, Alistair J. P., Lau, Benjamin Yii Chung, Cheah, Yoke Kqueen, Ho, Kok Lian, Sandai, Doblin, Yahaya, Hassan, and Than, Leslie Thian Lung

Subjects
bacterial infections and mycoses
Abstract

Additional file 1: Table S1. List of primers used in qPCR experiments. Table S2. Coefficient of determination (r2) between biological replicates for glucose- and acetate-grown C. glabrata. Table S3. List of enriched GO terms associated with up-regulated DEGs of acetate-grown C. glabrata cells. Table S4. List of enriched GO terms associated with down-regulated DEGs of acetate-grown C. glabrata cells. Table S5. List of enriched GO terms associated with DEPs of acetate-grown C. glabrata.

Published
2021
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45. The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives

Author

d'Enfert, Christophe, primary, Kaune, Ann-Kristin, additional, Alaban, Leovigildo-Rey, additional, Chakraborty, Sayoni, additional, Cole, Nathaniel, additional, Delavy, Margot, additional, Kosmala, Daria, additional, Marsaux, Benoît, additional, Fróis-Martins, Ricardo, additional, Morelli, Moran, additional, Rosati, Diletta, additional, Valentine, Marisa, additional, Xie, Zixuan, additional, Emritloll, Yoan, additional, Warn, Peter A, additional, Bequet, Frédéric, additional, Bougnoux, Marie-Elisabeth, additional, Bornes, Stephanie, additional, Gresnigt, Mark S, additional, Hube, Bernhard, additional, Jacobsen, Ilse D, additional, Legrand, Mélanie, additional, Leibundgut-Landmann, Salomé, additional, Manichanh, Chaysavanh, additional, Munro, Carol A, additional, Netea, Mihai G, additional, Queiroz, Karla, additional, Roget, Karine, additional, Thomas, Vincent, additional, Thoral, Claudia, additional, Van den Abbeele, Pieter, additional, Walker, Alan W, additional, and Brown, Alistair J P, additional

Published
2020
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47. Epitope Shaving Promotes Fungal Immune Evasion

Author

Childers, Delma S., primary, Avelar, Gabriela Mol, additional, Bain, Judith M., additional, Pradhan, Arnab, additional, Larcombe, Daniel E., additional, Netea, Mihai G., additional, Erwig, Lars P., additional, Gow, Neil A. R., additional, and Brown, Alistair J. P., additional

Published
2020
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