Review
Microbiology
Neil A. R. Cow, Megan D. Lenardon
Summary: The fungal cell wall is crucial for the growth and survival of fungi and is targeted by antifungal drugs and the immune system. The inner wall of most fungi is made up of chitin and beta-glucans, while the outer wall is composed of a variety of polymers and glycosylated proteins. Understanding the organization of fungal cell walls can lead to the development of diagnostics and drugs for combating fungal infections.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Austin Mottola, Bernardo Ramirez-Zavala, Kerstin Huenniger, Oliver Kurzai, Joachim Morschhaeuser
Summary: The fungal cell wall is crucial for cellular integrity and environmental interactions. A network of signaling pathways in Candida albicans regulates cell wall structure, with hyperactive Czf1 inducing the expression of cell wall-related genes and causing visible changes in cell wall architecture. Manipulation of Czf1 activity can influence the sensitivity of C. albicans to cell wall stress and antifungal drugs.
MOLECULAR MICROBIOLOGY
(2021)
Article
Microbiology
Andrew S. Wagner, Stephen W. Lumsdaine, Mikayla M. Mangrum, Todd B. Reynolds
Summary: To effectively induce disease, Candida albicans masks immunogenic β(1,3)-glucan epitopes within its cell wall under a layer of mannosylated glycoproteins. Treatment with the antifungal drug caspofungin enhances the exposure (unmasking) of β(1,3)-glucan, making the fungal cells more visible to the host immune system and attenuating disease progression. Our study reveals a correlation between increased chitin synthesis and β(1,3)-glucan unmasking in response to caspofungin, suggesting that altered chitin synthesis drives increased unmasking during drug exposure.
Article
Microbiology
Eunsoo Do, Max Cravener, Manning Y. Huang, Gemma May, C. Joel McManus, Aaron P. Mitchell
Summary: In this study, natural variation in the fungal pathogen Candida albicans was investigated to understand the gene regulatory control of biofilm formation, an important aspect of its virulence. Collaboration between the transcription factors Efg1 and Wor1 was found to drive natural variation in biofilm formation and gene expression. These findings highlight the importance of studying natural isolates to uncover unexpected features of gene function.
Article
Microbiology
Soumya Palliyil, Mark Mawer, Sami A. Alawfi, Lily Fogg, Tyng H. Tan, Giuseppe Buda De Cesare, Louise A. Walker, Donna M. MacCallum, Andrew J. Porter, Carol A. Munro
Summary: This study describes the early-stage development of monoclonal antibody-based immunotherapies for fungal infections. The researchers successfully generated recombinant human antibodies targeting specific cell wall proteins in Candida albicans and demonstrated their potential therapeutic effects by enhancing phagocytosis. Animal models showed that the lead antibody achieved improved survival and reduced fungal burden, surpassing the therapeutic efficacy of any previously reported anti-Candida antibody.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biology
Masataka Kawakita, Taiki Oyama, Ikuma Shirai, Shuto Tanaka, Kotaro Akaki, Shinya Abe, Takuma Asahi, Guangwei Cui, Fumie Itoh, Masato Sasaki, Nobuyuki Shibata, Koichi Ikuta, Tomomitsu Hatakeyama, Kazuhiko Takahara
Summary: Severe infections often lead to septic cytokine storms and immune exhaustion, but pathogens may have anti-inflammatory mechanisms that can be clinically leveraged. Research shows that N-glycan from pathogenic C. albicans can ameliorate sepsis in mice through IL-10, suppressing pro-inflammatory cytokines. This suggests a strategy where the immunosuppressive mechanism of one pathogen could potentially be used to mitigate inflammation caused by another pathogen.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jiawen Du, Yixuan Dong, He Zhao, Liping Peng, Yao Wang, Qilin Yu, Mingchun Li
Summary: In this study, the researchers identified the role of the Pho23 component in the Rpd3 HDAC complex in the transcriptional regulation of physiological processes in Candida albicans. Pho23 was found to regulate autophagic activity, cell wall stress resistance, hyphal development, protease secretion, and virulence in C. albicans.
Article
Biochemistry & Molecular Biology
Daria Derkacz, Przemyslaw Bernat, Anna Krasowska
Summary: The point mutation K143R in the ERG11 gene of azole-resistant Candida albicans contributes to azole resistance, increased gene expression, increased ergosterol content, and cell wall remodeling. This could lead to reduced susceptibility to azole treatment and a stronger immune response in the host.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Mohammad Tahseen AL Bataineh, Stefano Cacciatore, Mohammad Harb Semreen, Nihar Ranjan Dash, Nelson C. Soares, Xiaolong Zhu, Muath Khairi Mousa, Jasmin Shafarin Abdul Salam, Luiz F. Zerbini, Rima Hajjo, Mawieh Hamad
Summary: Increased levels of 17-beta estradiol (E2) due to pregnancy or hormonal replacement therapy have been associated with an increased risk of yeast infections. However, the underlying mechanism of E2 in Candida albicans infections is not well understood. This study found that E2 treatment in C. albicans cells leads to increased filament formation, but this effect is decreased when combined with serum treatment. Transcriptomic and metabolomic analyses revealed downregulation of genes involved in filamentation and glucose transport in cells treated with E2 and serum. Functional pathway analysis suggested the involvement of E2 signaling in metabolic pathways and secondary metabolite biosynthesis. These findings demonstrate the impact of E2 signaling on C. albicans morphogenesis and virulence.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Kang Xiong, Chang Su, Qiangqiang Sun, Yang Lu
Summary: CAS5 and EFG1 are key transcription factors in the transcriptional response to cell wall stress induced by Echinocandins, coregulating the expression of caspofungin-responsive genes while also independently controlling induction of some genes. Additionally, they bind to caspofungin-responsive gene promoters to coordinately activate their expression.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Applied
Ruilian Li, Limeng Zhu, Dongdong Liu, Wenjing Wang, Chen Zhang, Siming Jiao, Jinhua Wei, Lishi Ren, Yuchen Zhang, Xun Gou, Xianghua Yuan, Yuguang Du, Zhuo A. Wang
Summary: The study demonstrated that a cell wall polymer analog, HCOS, showed apparent antifungal activity against Candida strains, especially those in biofilm. Mechanistic studies suggested that HCOS exerts its activity by interfering with the connection and assembly of cell wall polysaccharides.
CARBOHYDRATE POLYMERS
(2022)
Article
Microbiology
Glaucia S. Arita, Daniella R. Faria, Isis R. G. Capoci, Erika S. Kioshima, Patricia S. Bonfim-Mendonca, Terezinha I. E. Svidzinski
Summary: This review focuses on the studies of C. albicans mutants for genes that encode cell wall-associated proteins, highlighting the importance of these proteins in virulence and hyphal morphogenesis. Some proteins with mutations are associated with attenuated virulence and defective filamentation, while others are still important for C. albicans virulence despite their inactivation not impairing filamentation.
MICROBIOLOGICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Fangyu Song, Wenshuo Zhang, Xiaohui Li, Xiaoqing Chen, Xuejun Yuan, Mingjin Jiang, Yunhe Zhao, Qingxin Liu, Zizhang Zhou
Summary: The main cause of high mortality in cancer patients is tumor metastasis, and exploring the underlying mechanism of tumor metastasis is important for clinical treatments. This study identifies the transcription factor Apt/FSBP as a suppressor for tumor metastasis, providing it as a potential drug target for tumor treatment.
Article
Microbiology
Xiaojuan Wang, Peng Liu, Yuanying Jiang, Bing Han, Lan Yan
Summary: Monoclonal antibodies targeting protein mannosyltransferase 4 of C. albicans have been found to be effective in alleviating symptoms and improving survival rate of candidiasis. These antibodies exert their immunotherapeutic effects through opsonophagocytosis and opsonic killing activity.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Wei-Chung Lai, Hsiao-Chi Hsu, Chun-Wen Cheng, Shao-Hung Wang, Wan Chen Li, Po-Szu Hsieh, Tzu-Ling Tseng, Ting-Hui Lin, Jia-Ching Shieh
Summary: We identified the Candida albicans GPH1 gene that is associated with the Cdc4 protein, and found that it contributes to cell wall function in C. albicans.
Article
Biochemistry & Molecular Biology
Mohit Kumar, Ashutosh Singh, Sonam Kumari, Praveen Kumar, Mohd Wasi, Alok K. Mondal, Shivaprakash M. Rudramurthy, Arunaloke Chakrabarti, Naseem A. Gaur, Neil A. R. Gow, Rajendra Prasad
Summary: Research indicates that sphingolipids influence the drug susceptibility of Candida auris. Analysis of drug-resistant clinical isolates of C. auris revealed that sphingolipid content may affect azole and amphotericin B susceptibilities. These findings provide insight into the dynamics of sphingolipid structures and their link to drug resistance in C. auris.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Cell Biology
Shabnam Sircaik, Elvira Roman, Priyanka Bapat, Keunsook K. Lee, David R. Andes, Neil A. R. Gow, Clarissa J. Nobile, Jesus Pla, Sneh Lata Panwar
Summary: The study demonstrates the crucial role of Ire1 in perceiving ER stress and activating UPR in Candida albicans. Additionally, compromised Ire1 function affects secretory homeostasis, antifungal tolerance, cell wall regulation, and virulence-related traits. Furthermore, Ire1 can activate UPR in response to perturbations in cell wall integrity and cell membrane homeostasis.
CELLULAR MICROBIOLOGY
(2021)
Article
Microbiology
Aiysha Thompson, Diogo M. da Fonseca, Louise Walker, James S. Griffiths, Philip R. Taylor, Neil A. R. Gow, Selinda J. Orr
Summary: Invasive Candida infections are mainly caused by four Candida species, and C-type lectin-like receptors (CLRs) are involved in the immune responses to these infections. Different Candida species have varying mannan contents in their cell walls, and Mincle and Dectin-2 play important roles in regulating cytokine production and clearance of these infections during systemic infection. Dependence on mannan-detecting CLRs varies between different Candida species during systemic infection.
FRONTIERS IN MICROBIOLOGY
(2021)
News Item
Biochemistry & Molecular Biology
Nicolas Papon, Gordon D. Brown, Neil A. R. Gow
Summary: The study suggests that dysbiosis of mycobiota can promote colon cancer by affecting energy metabolism in subepithelial macrophages, highlighting a potential role of gut flora in intestinal carcinogenesis and opportunities for preventative strategies involving antifungal or immunotherapeutic approaches.
Article
Genetics & Heredity
Nicolas Helmstetter, Aleksandra D. Chybowska, Christopher Delaney, Alessandra Da Silva Dantas, Hugh Gifford, Theresa Wacker, Carol Munro, Adilia Warris, Brian Jones, Christina A. Cuomo, Duncan Wilson, Gordon Ramage, Rhys A. Farrer
Summary: This study reveals the high genetic diversity of C. glabrata clinical isolates in Scotland, including multiple previously identified sequence types from around the world and a newly discovered sequence type. Ancient recombination events were found between different geographical regions, suggesting transmission and genetic exchange. The study also identifies genetic variations and microevolution related to drug resistance and virulence.
Meeting Abstract
Infectious Diseases
Arnab Pradhan, Qinxi Ma, Emer Hickey, Gabriela Avelar, Daniel Larcombe, Judith Bain, Delma Childers, Ivy Dambuza, Ian Leaves, Leandro Jose De Assis, Mihai Netea, Gordon Brown, Lars Erwig, Neil A. R. Gow, Alistair J. P. Brown
Meeting Abstract
Infectious Diseases
Neil A. R. Gow
Review
Microbiology
Neil A. R. Cow, Megan D. Lenardon
Summary: The fungal cell wall is crucial for the growth and survival of fungi and is targeted by antifungal drugs and the immune system. The inner wall of most fungi is made up of chitin and beta-glucans, while the outer wall is composed of a variety of polymers and glycosylated proteins. Understanding the organization of fungal cell walls can lead to the development of diagnostics and drugs for combating fungal infections.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Microbiology
Leandro Jose de Assis, Judith M. Bain, Corin Liddle, Ian Leaves, Christian Hacker, Roberta Peres da Silva, Raif Yuecel, Attila Bebes, David Stead, Delma S. Childers, Arnab Pradhan, Kevin Mackenzie, Katherine Lagree, Daniel E. Larcombe, Qinxi Ma, Gabriela Mol Avelar, Mihai G. Netea, Lars P. Erwig, Aaron P. Mitchell, Gordon D. Brown, Neil A. R. Gow, Alistair J. P. Brown
Summary: This study reveals that beta-1,3-glucan exposure on the surface of Candida albicans cells is targeted during phagocytosis, and lactate-induced masking reduces beta-1,3-glucan exposure. Downstream effectors of protein kinase A (PKA), Sin3 and Mig1/Mig2, regulate the secretion of glucanases and modulate beta-1,3-glucan exposure. Perturbing PKA, Sin3, or Mig1/Mig2 attenuates the virulence of lactate-exposed C. albicans cells.
Review
Multidisciplinary Sciences
Neil A. R. Gow, Carolyn Johnson, Judith Berman, Alix T. Coste, Christina A. Cuomo, David S. Perlin, Tihana Bicanic, Thomas S. Harrison, Nathan Wiederhold, Mike Bromley, Tom Chiller, Keegan Edgar
Summary: Prior to the SARS-CoV-2 pandemic, antibiotic resistance was considered a major global healthcare priority. Although fungal infections have not received enough public attention, the annual deaths caused by these infections are comparable to or even exceed the global mortalities due to malaria, tuberculosis, or HIV. The rise of antifungal drug resistant strains has worsened the impact of fungal infections on human health. This review aims to illuminate the problem of antifungal resistance and suggest possible measures to mitigate this growing threat.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Nicola T. Case, Judith Berman, David S. Blehert, Robert A. Cramer, Christina Cuomo, Cameron R. Currie, Iuliana Ene, Matthew C. Fisher, Lillian K. Fritz-Laylin, Aleeza C. Gerstein, N. Louise Glass, Neil A. R. Gow, Sarah J. Gurr, Chris Todd Hittinger, Tobias M. Hohl, Iliyan D. Iliev, Timothy Y. James, Hailing Jin, Bruce S. Klein, James W. Kronstad, Jeffrey M. Lorch, Victoria McGovern, Aaron P. Mitchell, Julia A. Segre, Rebecca S. Shapiro, Donald C. Sheppard, Anita Sil, Jason E. Stajich, Eva E. Stukenbrock, John W. Taylor, Dawn Thompson, Gerard D. Wright, Joseph Heitman, Leah E. Cowen
Summary: The fungal kingdom has diverse impacts on animal, plant, and ecosystem health, supporting life while also causing diseases. With increased climate change, antimicrobial resistance, and other global challenges, it is crucial to develop new approaches to combat fungal threats and harness their potential. This report provides recommendations and highlights major research advances and ideas discussed at a workshop to address these challenges.
G3-GENES GENOMES GENETICS
(2022)
Article
Biotechnology & Applied Microbiology
Dora E. Corzo Leon, Annika Scheynius, Donna M. MacCallum, Carol A. Munro
FEMS YEAST RESEARCH
(2023)
Article
Microbiology
Liviana Ricci, Joanna Mackie, Gillian E. Donachie, Ambre Chapuis, Kristyna Mezerova, Megan D. Lenardon, Alistair J. P. Brown, Sylvia H. Duncan, Alan W. Walker
Summary: This study found variations in the ability of gut microbiota to inhibit the fungal pathogen Candida albicans. Bifidobacteria and their fermentation acids were identified as important components in inhibitory gut microbiota. The findings provide insights into the potential mechanisms of gut microbiome-mediated colonization resistance against Candida albicans and suggest bifidobacteria and fermentation acids as targets for further study.
FEMS MICROBIOLOGY ECOLOGY
(2022)
Article
Mycology
Emily M. Stevenson, William H. Gaze, Neil A. R. Gow, Alwyn Hart, Wiebke Schmidt, Jane Usher, Adilia Warris, Helen Wilkinson, Aimee K. Murray
Summary: This scoping review examines the current understanding of selection for antifungal resistance (AFR) and compares it with selection for antibacterial resistance. AFR is an emerging global threat to human health, with high mortality rates and limited treatment options. The review highlights the need for assessment of antifungal agents in environmental risk assessment guidelines and suggests potential methods to determine antifungal selective concentrations.
FRONTIERS IN FUNGAL BIOLOGY
(2022)
