Human fungal pathogens that cause invasive infections are
hidden killers, taking lives of one and a half million people
every year. However, research progress in this field has not
been rapid enough to effectively prevent or treat life-threatening
fungal diseases. To update recent research progress
and promote more active research in the field of human fungal
pathogens, eleven review articles concerning the virulence
mechanisms and host interactions of four major human fungal
pathogens–Candida albicans, Cryptococcus neoformans,
Aspergillus fumigatus, and Histoplasma capsulatum–are
presented in this special issue.
Citations
Citations to this article as recorded by
Comprehensive Insights into Sugar Transporters of Candidozyma auris and Their Roles in Antifungal Resistance Praveen Kumar, Mohit Kumar, Amandeep Saini, Sheikh Owais Mohamad, Basharat Ali, Brooke D. Esquivel, Atanu Banerjee, Theodore C. White, Naseem A. Gaur, Abdul Haseeb Shah, Amresh Prakash, Rajendra Prasad Journal of Fungi.2026; 12(2): 94. CrossRef
A systematic review to understand the current scenarios employing plants and their secondary metabolites as antifungal agents: opportunities and challenges Shivangani, Hariprasad P․ South African Journal of Botany.2026; 189: 143. CrossRef
Endophytic nanotechnology as a dual-action approach against agricultural and clinical fungal pathogens Aishwarya Sharma, Eti Sharma Archives of Microbiology.2026;[Epub] CrossRef
Chemical profile, antioxidant, antifungal, and cytotoxic activities of propolis from the stingless bee Tetragona clavipes Ariane Pinheiro Cruz Bergamini, Brendo Victor Siqueira de Almeida Bergamini, Iana Soares Pessoa, Thiago Antônio de Sousa Cutrim, Tamires Cruz dos Santos, Matheus Campos dos Santos, Victor da Rocha Fonseca, Wanderson Romão, Rodrigo Scherer, Denise Coutinho Brazilian Journal of Microbiology.2025; 56(1): 251. CrossRef
The unfolded protein response is a potential therapeutic target in pathogenic fungi Hao Zhou, Jinping Zhang, Rong Wang, Ju Huang, Caiyan Xin, Zhangyong Song The FEBS Journal.2025; 292(19): 5008. CrossRef
Formulation Optimization and Characterization of Bifonazole-Loaded Transethosomal Gel by 32 Factorial Design for the Treatment of Topical Fungal Infection Umeshkumar Dinesh Patel, Vinayak Shivamurthi Mastiholimath BioNanoScience.2025;[Epub] CrossRef
Evaluation of Ultraviolet Light-Based Oxidative Systems for the Inactivation and Change in Susceptibility of a Fluconazole-Resistant Candida albicans Strain Luz Dary Caicedo-Bejarano, Adriana María Correa-Bermúdez, Sandra Patricia Castro-Narváez, Efraím A. Serna-Galvis Water.2025; 17(16): 2448. CrossRef
Reactive Halogen Species Boost Fungal Spore Inactivation in Seawater during UV/PMS Treatment Ye Chen, Muke Lin, Zhuoyun Tang, Yuqin Wang, Dehua Xia, Zhechao Hua, Jingyun Fang, Ran Yin Environmental Science & Technology.2025; 59(36): 19537. CrossRef
Transferosomes As A Promising Platform for Targeted Antifungal Drug Delivery Yashmi Jain, Geetika Jain, Dakshita Dutta, Manish Yadav Current Fungal Infection Reports.2025;[Epub] CrossRef
Torsade de Pointes and QT Prolongation Among Antifungal Triazoles: A Real-World, Retrospective, Observational, Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS) Database Long Chen, Ming-Jia Liu, Song Wang, Dan Yang, Nan-Nan Ding, Ji Zhang Cardiovascular Toxicology.2025; 25(10): 1616. CrossRef
Humans vs. Fungi: An Overview of Fungal Pathogens against Humans Kasun M. Thambugala, Dinushani A. Daranagama, Danushka S. Tennakoon, Dona Pamoda W. Jayatunga, Sinang Hongsanan, Ning Xie Pathogens.2024; 13(5): 426. CrossRef
Active monitoring of antifungal adverse events in hospitalized patients based on Global Trigger Tool method Xiao Meng, Yaozhou Wu, Zixuan Liu, Yifan Chen, Zhizhou Dou, Li Wei Frontiers in Pharmacology.2024;[Epub] CrossRef
Interplay of host-immunity in fungal eye infections Piyush Baindara, Santi M. Mandal Fungal Biology Reviews.2024; 48: 100357. CrossRef
Cytotoxicity, antifungal and antioxidant properties of Lonchocarpus capassa leaf extracts Tambudzani C. Machaba, Salome Mahlo, Jacobus Eloff, Winston Nxumalo, Lyndy McGaw Journal of Medicinal Plants for Economic Development.2024;[Epub] CrossRef
Alternative and Classical Processes for Disinfection of Water Polluted by Fungi: A Systematic Review Luz Dary Caicedo-Bejarano, Alejandra Morante-Caicedo, Sandra Patricia Castro-Narváez, Efraím A. Serna-Galvis Water.2024; 16(7): 936. CrossRef
IRF7 Exacerbates Candida albicans Infection by Compromising CD209-Mediated Phagocytosis and Autophagy-Mediated Killing in Macrophages Furong Qing, Lina Sui, Wenji He, Yayun Chen, Li Xu, Liangmei He, Qiuxiang Xiao, Tianfu Guo, Zhiping Liu The Journal of Immunology.2024; 212(12): 1932. CrossRef
Verapamil enhances the activity of Caspofungin against Cryptococcus neoformans, coinciding with inhibited Ca2+/CN pathway and damage to cell wall integrity Xinyuan Peng, Qingtao Kong, Qian Wei, Shilin Guo, Qiying Chen, Min Peng, Binyi An, Xiaoyu Wang, Chen Zhang, Hong Sang International Journal of Antimicrobial Agents.2024; 64(4): 107303. CrossRef
Cathelicidin boosts the antifungal activity of neutrophils and improves prognosis during
Aspergillus fumigatus
keratitis
Xiaochen Hou, Cui Li, Jingyi Liu, Shanshan Yang, Xudong Peng, Qian Wang, Chengxiu Liu, Xing Liu, Junjie Luan, Guiqiu Zhao, Jing Lin, Mairi C. Noverr Infection and Immunity.2024;[Epub] CrossRef
Development, Optimization, and In Vitro/In Vivo Evaluation of Azelaic Acid Transethosomal Gel for Antidermatophyte Activity Ali M. Nasr, Noha M. Badawi, Yasmine H. Tartor, Nader M. Sobhy, Shady A. Swidan Antibiotics.2023; 12(4): 707. CrossRef
PU.1-CD23 signaling mediates pulmonary innate immunity against Aspergillus fumigatus infection by driving inflammatory response Min Wang, Ming Zhang, Jiayong Qiu, Chenyang Liu, Yao Lou, Tongsheng Wang, Yingmin Zhang, Yimin Mao BMC Immunology.2023;[Epub] CrossRef
Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry azole susceptibility assessment in Candida and Aspergillus species Ana Luisa Perini Leme Giordano, Lais Pontes, Caio Augusto Gualtieri Beraquet, Luzia Lyra, Angelica Zaninelli Schreiber Memórias do Instituto Oswaldo Cruz.2023;[Epub] CrossRef
A parallel and silent emerging pandemic: Antimicrobial resistance (AMR) amid COVID-19 pandemic Suriya Rehman Journal of Infection and Public Health.2023; 16(4): 611. CrossRef
Current Insights in Fungal Importance—A Comprehensive Review Viorica Maria Corbu, Irina Gheorghe-Barbu, Andreea Ștefania Dumbravă, Corneliu Ovidiu Vrâncianu, Tatiana Eugenia Șesan Microorganisms.2023; 11(6): 1384. CrossRef
Clinical infections in neurosurgical oncology: An overview Tomaz Velnar, Nina Kocivnik, Roman Bosnjak World Journal of Clinical Cases.2023; 11(15): 3418. CrossRef
The effect of herbal medicine in innate immunity to Candida albicans Meng-Yuan Bao, Ming Li, Qing-Ru Bu, Yue Yang, Hang Song, Chang-Zhong Wang, Tian-Ming Wang, Ning Li Frontiers in Immunology.2023;[Epub] CrossRef
Betulinic acid and Drummondin E: Potential inhibitors of Unfolded Protein Response Pathway of Candida auris Nahid Akhtar, Amit Joshi, Vikas Kaushik, Sangeetha Mohan, M. Amin-ul Mannan Research Journal of Pharmacy and Technology.2023; : 2867. CrossRef
Understanding the Roles of Host Defense Peptides in Immune Modulation: From Antimicrobial Action to Potential as Adjuvants Ju Kim, Byeol-Hee Cho, Yong-Suk Jang Journal of Microbiology and Biotechnology.2023; 33(3): 288. CrossRef
Bacillus Metabolites: Compounds, Identification and Anti-Candida albicans Mechanisms Weichen Wang, Jin Zhao, Zhizi Zhang Microbiology Research.2022; 13(4): 972. CrossRef
Uncommon case of histoplasmosis with oral manifestation Letícia Copatti Dogenski, Eduarda Mafaciolli Pasqualotto, Mateus José Dutra, Gisele Rovani, Micheline Sandini Trentin, João Paulo De Carli International Journal of Surgery Case Reports.2022; 93(C): 106920. CrossRef
Oral delivery of butoconazole nitrate nanoparticles for systemic treatment of chronic paracoccidioidomycosis: A future aspect Tasleem, Nithya Shanthi, Arun Kumar Mahato, Richa Bahuguna Journal of Drug Delivery Science and Technology.2022; 77: 103808. CrossRef
Time to Conquer Fungal Infectious Diseases: Employing Nanoparticles as Powerful and Versatile Antifungal Nanosystems against a Wide Variety of Fungal Species Ali Jangjou, Zahra Zareshahrabadi, Milad Abbasi, Amirreza Talaiekhozani, Hesam Kamyab, Shreeshivadasan Chelliapan, Ahmad Vaez, Ali Golchin, Lobat Tayebi, Ehsan Vafa, Ali Mohammad Amani, Hossein Faramarzi Sustainability.2022; 14(19): 12942. CrossRef
Does the technical methodology influence the quality attributes and the potential of skin permeation of Luliconazole loaded transethosomes? Mahmoud M. El-Sonbaty, Mohamed A. Akl, Khalid M. El-Say, Alaa A. Kassem Journal of Drug Delivery Science and Technology.2022; 68: 103096. CrossRef
Guanylated Hyperbranched Polylysines with High In Vitro and In Vivo Antifungal Activity Xiao Liu, Yilong Yang, Miaomiao Han, Jianwei Guo, Hui Liu, Yadong Liu, Junjie Xu, Shengxiang Ji, Xuesi Chen Advanced Healthcare Materials.2022;[Epub] CrossRef
The Role of the Glutathione System in Stress Adaptation, Morphogenesis and Virulence of Pathogenic Fungi Tanaporn Wangsanut, Monsicha Pongpom International Journal of Molecular Sciences.2022; 23(18): 10645. CrossRef
HDAC11 negatively regulates antifungal immunity by inhibiting Nos2 expression via binding with transcriptional repressor STAT3 Han Wu, Xiaofan Yin, Xibao Zhao, Zherui Wu, Yue Xiao, Qianqian Di, Ping Sun, Haimei Tang, Jiazheng Quan, Weilin Chen Redox Biology.2022; 56: 102461. CrossRef
Pre-Exposure With Extracellular Vesicles From Aspergillus fumigatus Attenuates Inflammatory Response and Enhances Fungal Clearance in a Murine Model Pulmonary Aspergillosis Jéssica Amanda Marques Souza, Isabella Luísa da Silva Gurgel, Nathália Luísa Sousa de Oliveira Malacco, Flávia Rayssa Braga Martins, Celso Martins Queiroz-Junior, Mauro Martins Teixeira, Frederico Marianetti Soriani Frontiers in Cellular and Infection Microbiology.2022;[Epub] CrossRef
The emerging role of neutrophil extracellular traps in fungal infection Chuting Liang, Ni Lian, Min Li Frontiers in Cellular and Infection Microbiology.2022;[Epub] CrossRef
Permanent, Antimicrobial Coating to Rapidly Kill and Prevent Transmission of Bacteria, Fungi, Influenza, and SARS-CoV-2 Sreyan Ghosh, Riya Mukherjee, Vinay S. Mahajan, Julie Boucau, Shiv Pillai, Jayanta Haldar ACS Applied Materials & Interfaces.2022; 14(37): 42483. CrossRef
Antifungal Activity of the Frog Skin Peptide Temporin G and Its Effect on Candida albicans Virulence Factors Felicia Diodata D’Auria, Bruno Casciaro, Marta De Angelis, Maria Elena Marcocci, Anna Teresa Palamara, Lucia Nencioni, Maria Luisa Mangoni International Journal of Molecular Sciences.2022; 23(11): 6345. CrossRef
WITHDRAWN: Fatty acid dioxygenase-cytochrome P450 fusion enzymes of the top 10 fungal pathogens in molecular plant pathology and human-pathogenic fungi Ernst H. Oliw Fungal Genetics and Biology.2021; : 103603. CrossRef
MYO1F regulates antifungal immunity by regulating acetylation of microtubules Wanwei Sun, Xiaojian Ma, Heping Wang, Yanyun Du, Jianwen Chen, Huijun Hu, Ru Gao, Ruirui He, Qianwen Peng, Zhihui Cui, Huazhi Zhang, Junhan Wang, Xinming Jia, Bradley N. Martin, Cun-Jin Zhang, Xiaoxia Li, Chenhui Wang Proceedings of the National Academy of Sciences.2021;[Epub] CrossRef
Solubility enhancement, formulation development and antifungal activity of luliconazole niosomal gel-based system Ashish Kumar Garg, Balaji Maddiboyina, Mohammed Hamed Saeed Alqarni, Aftab Alam, Hibah M. Aldawsari, Pinki Rawat, Sima Singh, Prashant Kesharwani Journal of Biomaterials Science, Polymer Edition.2021; 32(8): 1009. CrossRef
Preclinical safety evaluation of amphotericin A21: A novel antifungal Ivan Ortega‐Blake, Mario Fernández‐Zertuche, Ignacio Regla, Walfred Sánchez‐Peña, Antonieta Gómez‐Solis, Paola Jaimes‐Chavez, Arturo Galván‐Hernández, Erika Tovar‐Garduño, Lourdes Rodríguez‐Fragoso Basic & Clinical Pharmacology & Toxicology.2021; 129(1): 72. CrossRef
Antimicrobial Peptides: The Promising Therapeutics for Cutaneous Wound Healing Fengze Miao, Ying Li, Zongguang Tai, Yong Zhang, Yue Gao, Menghong Hu, Quangang Zhu Macromolecular Bioscience.2021;[Epub] CrossRef
The transcription factor Cas5 suppresses hyphal morphogenesis during yeast-form growth in Candida albicans Jong-Myeong Kim, Hye Yun Moon, Dong Wook Lee, Hyun Ah Kang, Jeong-Yoon Kim Journal of Microbiology.2021; 59(10): 911. CrossRef
Antifungal activity of thiosemicarbazones, bis(thiosemicarbazones), and their metal complexes Kritika Bajaj, Robert M. Buchanan, Craig A. Grapperhaus Journal of Inorganic Biochemistry.2021; 225: 111620. CrossRef
Fatty acid dioxygenase-cytochrome P450 fusion enzymes of filamentous fungal pathogens Ernst H. Oliw Fungal Genetics and Biology.2021; 157: 103623. CrossRef
Membrane-Interacting Antifungal Peptides Caroline Struyfs, Bruno P. A. Cammue, Karin Thevissen Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
Aspergillus fumigatus In-Host HOG Pathway Mutation for Cystic Fibrosis Lung Microenvironment Persistence Brandon S. Ross, Lotus A. Lofgren, Alix Ashare, Jason E. Stajich, Robert A. Cramer, J. Andrew Alspaugh mBio.2021;[Epub] CrossRef
Nanomaterial-Based Antifungal Therapies to Combat Fungal Diseases Aspergillosis, Coccidioidomycosis, Mucormycosis, and Candidiasis Angel León-Buitimea, Javier A. Garza-Cervantes, Diana Y. Gallegos-Alvarado, Macario Osorio-Concepción, José Ruben Morones-Ramírez Pathogens.2021; 10(10): 1303. CrossRef
Cathelicidin-inspired antimicrobial peptides as novel antifungal compounds Martin van Eijk, Stephanie Boerefijn, Lida Cen, Marisela Rosa, Marnix J H Morren, Cornelis K van der Ent, Bart Kraak, Jan Dijksterhuis, Ivan D Valdes, Henk P Haagsman, Hans de Cock Medical Mycology.2020; 58(8): 1073. CrossRef
Broad-Spectrum Antimicrobial and Antibiofilm Activity of a Natural Clay Mineral from British Columbia, Canada Shekooh Behroozian, Sarah L. Svensson, Loretta Y. Li, Julian E. Davies, Pascale F. Cossart mBio.2020;[Epub] CrossRef
Antimicrobial host defence peptides: functions and clinical potential Neeloffer Mookherjee, Marilyn A. Anderson, Henk P. Haagsman, Donald J. Davidson Nature Reviews Drug Discovery.2020; 19(5): 311. CrossRef
Alteration of Fermentative Metabolism Enhances Mucor circinelloides Virulence Sharel P. Díaz-Pérez, J. Alberto Patiño-Medina, Marco I. Valle-Maldonado, Adolfo López-Torres, Irvin E. Jácome-Galarza, Verónica Anaya-Martínez, Verónica Gómez-Ruiz, Jesús Campos-García, Rosa E. Nuñez-Anita, Rafael Ortiz-Alvarado, Martha I. Ramírez-Díaz, Infection and Immunity.2020;[Epub] CrossRef
Fungal evolution: major ecological adaptations and evolutionary transitions Miguel A. Naranjo‐Ortiz, Toni Gabaldón Biological Reviews.2019; 94(4): 1443. CrossRef
Acute Lung Injury and Repair Induced by Single Exposure of
Aspergillus Fumigatus
in Immunocompetent Mice
Nathália L S O Malacco, Jéssica A M Souza, Aline C Mendes, Milene A Rachid, Lucas R Kraemer, Matheus S Mattos, Graziele N Lima, Lirlândia P Sousa, Daniele G Souza, Vanessa Pinho, Mauro M Teixeira, Remo C Russo, Frederico M Soriani Future Microbiology.2019; 14(17): 1511. CrossRef
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Glycobiology of Human Fungal Pathogens: New Avenues for Drug Development Danielle J. Lee, Holly O’Donnell, Françoise H. Routier, Joe Tiralongo, Thomas Haselhorst Cells.2019; 8(11): 1348. CrossRef
Fungal dissemination is limited by liver macrophage filtration of the blood Donglei Sun, Peng Sun, Hongmei Li, Mingshun Zhang, Gongguan Liu, Ashley B. Strickland, Yanli Chen, Yong Fu, Juan Xu, Mohammed Yosri, Yuchen Nan, Hong Zhou, Xiquan Zhang, Meiqing Shi Nature Communications.2019;[Epub] CrossRef
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Comparison of Two Molecular Assays for Detection and Characterization of Aspergillus fumigatus Triazole Resistance and Cyp51A Mutations in Clinical Isolates and Primary Clinical Samples of Immunocompromised Patients Patricia Postina, Julian Skladny, Tobias Boch, Oliver A. Cornely, Axel Hamprecht, Peter-Michael Rath, Jörg Steinmann, Oliver Bader, Thomas Miethke, Anne Dietz, Natalia Merker, Wolf-Karsten Hofmann, Dieter Buchheidt, Birgit Spiess Frontiers in Microbiology.2018;[Epub] CrossRef
Cryptic Aspergillus from clinical samples in the USA and description of a new species in section Flavipedes João P. Z. Siqueira, Nathan Wiederhold, Josepa Gené, Dania García, Margarete T. G. Almeida, Josep Guarro Mycoses.2018; 61(11): 814. CrossRef
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Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity Dayanira Alsina‐Beauchamp, Alejandra Escós, Pilar Fajardo, Diego González‐Romero, Ester Díaz‐Mora, Ana Risco, Miguel A Martín‐Serrano, Carlos del Fresno, Jorge Dominguez‐Andrés, Noelia Aparicio, Rafal Zur, Natalia Shpiro, Gordon D Brown, Carlos Ardavín, M EMBO Molecular Medicine.2018;[Epub] CrossRef
The Interaction of Human Pathogenic Fungi With C-Type Lectin Receptors Surabhi Goyal, Juan Camilo Castrillón-Betancur, Esther Klaile, Hortense Slevogt Frontiers in Immunology.2018;[Epub] CrossRef
Identification of Fungal Species in Brain Tissue from Alzheimer’s Disease by Next-Generation Sequencing Ruth Alonso, Diana Pisa, Begoña Aguado, Luis Carrasco Journal of Alzheimer's Disease.2017; 58(1): 55. CrossRef
Nanoparticles as safe and effective delivery systems of antifungal agents: Achievements and challenges Ghareb M. Soliman International Journal of Pharmaceutics.2017; 523(1): 15. CrossRef
Conclusion and future perspectives on antifungal stewardship Jose María Aguado, Jose Tiago Silva, Emilio Bouza Journal of Antimicrobial Chemotherapy.2016; 71(suppl 2): ii43. CrossRef
The interaction between Candida albicans and its host cells is
characterized by a complex interplay between the expression
of fungal virulence factors, which results in adherence, invasion
and cell damage, and the host immune system, which
responds by secreting proinflammatory cytokines, activating
antimicrobial activities and killing the fungal pathogen. In
this review we describe this interplay by taking a closer look
at how C. albicans pathogenicity is induced and executed,
how the host responds in order to prevent and clear an infection,
and which mechanisms C. albicans has evolved to
bypass these immune responses to avoid clearance. Furthermore,
we review studies that show how the presence of other
microorganisms affects this interplay.
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The fungal human pathogen Candida albicans can cause invasive
infection with high mortality rates. A key virulence
factor is its ability to switch between three morphologies:
yeast, pseudohyphae and hyphae. In contrast to the ovalshaped
unicellular yeast cells, hyphae are highly elongated,
tube-like, and multicellular. A long-standing question is what
coordinates all the cellular machines to construct cells with
distinct shapes. Hyphal-specific genes (HSGs) are thought
to hold the answer. Among the numerous HSGs found, only
UME6 and HGC1 are required for hyphal development.
UME6 encodes a transcription factor that regulates many
HSGs including HGC1. HGC1 encodes a G1 cyclin which
partners with the Cdc28 cyclin-dependent kinase. Hgc1-
Cdc28 simultaneously phosphorylates and regulates multiple
substrates, thus controlling multiple cellular apparatuses for
morphogenesis. This review is focused on major progresses
made in the past decade on Hgc1’s roles and regulation in
C. albicans hyphal development and other traits important
for infection.
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Candida albicans is a human fungal pathogen capable of causing
lethal systemic infections. The plasma membrane plays key
roles in virulence because it not only functions as a protective
barrier, it also mediates dynamic functions including secretion
of virulence factors, cell wall synthesis, invasive hyphal
morphogenesis, endocytosis, and nutrient uptake. Consistent
with this functional complexity, the plasma membrane is
composed of a wide array of lipids and proteins. These components
are organized into distinct domains that will be the
topic of this review. Some of the plasma membrane domains
that will be described are known to act as scaffolds or barriers
to diffusion, such as MCC/eisosomes, septins, and sites
of contact with the endoplasmic reticulum. Other zones mediate
dynamic processes, including secretion, endocytosis, and
a special region at hyphal tips that facilitates rapid growth.
The highly organized architecture of the plasma membrane
facilitates the coordination of diverse functions and promotes
the pathogenesis of C. albicans.
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Fungal cell membrane-promising drug target for antifungal therapy D.G. Sant, S.G. Tupe, C.V. Ramana, M.V. Deshpande Journal of Applied Microbiology.2016; 121(6): 1498. CrossRef
The yeast Candida albicans is a member of the microbiota
in the gastrointestinal and urogenital tracts of most healthy
persons, but it can also cause symptomatic infections, especially
in immunocompromised patients. During the life-long
association with its human host, C. albicans generates genetically
altered variants that are better adapted to changes in
their environment. A prime example of this microevolution
is the development of resistance to the commonly used drug
fluconazole, which inhibits ergosterol biosynthesis, during
antimycotic therapy. Fluconazole resistance can be caused by
mutations in the drug target, by changes in the sterol biosynthesis
pathway, and by gain-of-function mutations in transcription
factors that result in the constitutive upregulation
of ergosterol biosynthesis genes and multidrug efflux pumps.
Fluconazole also induces genomic rearrangements that result
in gene amplification and loss of heterozygosity for resistance
mutations, which further increases drug resistance.
These genome alterations may affect extended chromosomal
regions and have additional phenotypic consequences. A
striking case is the loss of heterozygosity for the mating type
locus MTL in many fluconazole-resistant clinical isolates,
which allows the cells to switch to the mating-competent opaque
phenotype. This, in turn, raises the possibility that sexual
recombination between different variants of an originally clonal,
drug-susceptible population may contribute to the generation
of highly fluconazole-resistant strains with multiple
resistance mechanisms. The gain-of-function mutations in
transcription factors, which result in deregulated gene expression,
also cause reduced fitness. In spite of this, many clinical
isolates that contain such mutations do not exhibit fitness defects,
indicating that they have overcome the costs of drug
resistance with further evolution by still unknown mechanisms.
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Cryptococcus neoformans, the predominant etiological agent
of cryptococcosis, can cause life-threatening infections of the
central nervous system in immunocompromised and immunocompetent
individuals. Cryptococcal meningoencephalitis
is the most common disseminated fungal infection in AIDS
patients, and remains the third most common invasive fungal
infection among organ transplant recipients. The administration
of highly active antiretroviral therapy (HAART) has result ed in a decrease in the number of cases of AIDS-related
cryptococcosis in developed countries, but in developing
countries where HAART is not readily available, Cryptococcus
is still a major concern. Therefore, there is an urgent
need for the development of novel therapies and/or vaccines
to combat cryptococcosis. Understanding the protective immune
responses against Cryptococcus is critical for development
of vaccines and immunotherapies to combat cryptococcosis.
Consequently, this review focuses on our current
knowledge of protective immune responses to C. neoformans,
with an emphasis on innate immune responses.
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Lipid modification of proteins is a widespread, essential process
whereby fatty acids, cholesterol, isoprenoids, phospholipids,
or glycosylphospholipids are attached to polypeptides.
These hydrophobic groups may affect protein structure, function,
localization, and/or stability; as a consequence such modifications
play critical regulatory roles in cellular systems.
Recent advances in chemical biology and proteomics have
allowed the profiling of modified proteins, enabling dissection
of the functional consequences of lipid addition. The
enzymes that mediate lipid modification are specific for both
the lipid and protein substrates, and are conserved from fungi
to humans. In this article we review these enzymes, their substrates,
and the processes involved in eukaryotic lipid modification
of proteins. We further focus on its occurrence in
the fungal pathogen Cryptococcus neoformans, highlighting
unique features that are both relevant for the biology of the
organism and potentially important in the search for new
therapies.
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The filamentous fungus Aspergillus fumigatus is the most prevalent
airborne fungal pathogen causing severe and usually
fatal invasive aspergillosis in immunocompromised patients.
This fungus produces a large number of small hydrophobic
asexual spores called conidia as the primary means of reproduction,
cell survival, propagation, and infectivity. The initiation,
progression, and completion of asexual development
(conidiation) is controlled by various regulators that govern
expression of thousands of genes associated with formation
of the asexual developmental structure conidiophore, and
biogenesis of conidia. In this review, we summarize key regulators
that directly or indirectly govern conidiation in this
important pathogenic fungus. Better understanding these
developmental regulators may provide insights into the improvement
in controlling both beneficial and detrimental
aspects of various Aspergillus species.
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Over the past several decades, research on the synthesis and
organization of the cell wall polysaccharides of Aspergillus
fumigatus has expanded our knowledge of this important
fungal structure. Besides protecting the fungus from environmental
stresses and maintaining structural integrity of
the organism, the cell wall is also the primary site for interaction
with host tissues during infection. Cell wall polysaccharides
are important ligands for the recognition of fungi
by the innate immune system and they can mediate potent
immunomodulatory effects. The synthesis of cell wall polysaccharides
is a complicated process that requires coordinated
regulation of many biosynthetic and metabolic pathways.
Continuous synthesis and remodeling of the polysaccharides
of the cell wall is essential for the survival of the
fungus during development, reproduction, colonization and
invasion. As these polysaccharides are absent from the human
host, these biosynthetic pathways are attractive targets
for antifungal development. In this review, we present recent
advances in our understanding of Aspergillus fumigatus cell
wall polysaccharides, including the emerging role of cell
wall polysaccharides in the host-pathogen interaction.
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Quantitative Monitoring of Mycelial Growth of Aspergillus fumigatus in Liquid Culture by Optical Density Ken Miyazawa, Takashi Umeyama, Yasutaka Hoshino, Keietsu Abe, Yoshitsugu Miyazaki, Slavena Vylkova, Xiaoxiao He, Takuji Oka Microbiology Spectrum.2022;[Epub] CrossRef
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MicroRNA regulation and host interaction in response to Aspergillus exposure MANSI SHRIVASTAVA, DIKSHA PANDEY, POONAM SHARMA, RAMBIR SINGH BIOCELL.2022; 46(2): 339. CrossRef
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Online Biomass Monitoring Enables Characterization of the Growth Pattern of Aspergillus fumigatus in Liquid Shake Conditions Ingo Bauer, Beate Abt, Annie Yap, Bernd Leuchtle, Hubertus Haas Journal of Fungi.2022; 8(10): 1013. CrossRef
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Both Galactosaminogalactan and α-1,3-Glucan Contribute to Aggregation of Aspergillus oryzae Hyphae in Liquid Culture Ken Miyazawa, Akira Yoshimi, Motoaki Sano, Fuka Tabata, Asumi Sugahara, Shin Kasahara, Ami Koizumi, Shigekazu Yano, Tasuku Nakajima, Keietsu Abe Frontiers in Microbiology.2019;[Epub] CrossRef
Aspergillus fumigatus Mnn9 is responsible for mannan synthesis and required for covalent linkage of mannoprotein to the cell wall Ting Du, Haomiao Ouyang, Josef Voglmeir, Iain B.H. Wilson, Cheng Jin Fungal Genetics and Biology.2019; 128: 20. CrossRef
Aspergillus fumigatus phosphoethanolamine transferase gene gpi7 is required for proper transportation of the cell wall GPI-anchored proteins and polarized growth Haomiao Ouyang, Ting Du, Hui Zhou, Iain B. H. Wilson, Jinghua Yang, Jean-Paul Latgé, Cheng Jin Scientific Reports.2019;[Epub] CrossRef
Klebsiella pneumoniae prevents spore germination and hyphal development of Aspergillus species M. F. Nogueira, L. Pereira, S. Jenull, K. Kuchler, T. Lion Scientific Reports.2019;[Epub] CrossRef
Overexpression of Aspergillus nidulans α-1,3-glucan synthase increases cellular adhesion and causes cell wall defects Xiaoxiao He, Shengnan Li, Susan G W Kaminskyj Medical Mycology.2018; 56(5): 645. CrossRef
The Aspergillus fumigatus Sialidase (Kdnase) Contributes to Cell Wall Integrity and Virulence in Amphotericin B-Treated Mice Jason R. Nesbitt, Elizabeth Y. Steves, Cole R. Schonhofer, Alissa Cait, Sukhbir S. Manku, Juliana H. F. Yeung, Andrew J. Bennet, Kelly M. McNagny, Jonathan C. Choy, Michael R. Hughes, Margo M. Moore Frontiers in Microbiology.2018;[Epub] CrossRef
Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in
Aspergillus fumigatus
Leandro José de Assis, Adriana Manfiolli, Eliciane Mattos, João H. T. Marilhano Fabri, Iran Malavazi, Ilse D. Jacobsen, Matthias Brock, Robert A. Cramer, Arsa Thammahong, Daisuke Hagiwara, Laure Nicolas Annick Ries, Gustavo Henrique Goldman, Reinhard Fisc mBio.2018;[Epub] CrossRef
A Ring Contraction of 2,3-Di-O-Silylated Thiopyranosides To Give Thiofuranosides under Mildly Acidic Conditions Polina I. Abronina, Nelly N. Malysheva, Veronika V. Litvinenko, Alexander I. Zinin, Natalya G. Kolotyrkina, Leonid O. Kononov Organic Letters.2018; 20(19): 6051. CrossRef
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Molecular Mass and Localization of α-1,3-Glucan in Cell Wall Control the Degree of Hyphal Aggregation in Liquid Culture of Aspergillus nidulans Ken Miyazawa, Akira Yoshimi, Shin Kasahara, Asumi Sugahara, Ami Koizumi, Shigekazu Yano, Satoshi Kimura, Tadahisa Iwata, Motoaki Sano, Keietsu Abe Frontiers in Microbiology.2018;[Epub] CrossRef
Aspergillusin chronic lung disease: Modeling what goes on in the airways Takahiro Takazono, Donald C. Sheppard Medical Mycology.2017; 55(1): 39. CrossRef
Sporothrix schenckii sensu stricto and Sporothrix brasiliensis Are Differentially Recognized by Human Peripheral Blood Mononuclear Cells José A. Martínez-Álvarez, Luis A. Pérez-García, Erika Mellado-Mojica, Mercedes G. López, Iván Martínez-Duncker, Leila M. Lópes-Bezerra, Héctor M. Mora-Montes Frontiers in Microbiology.2017;[Epub] CrossRef
Immune responses to invasive aspergillosis: new understanding and therapeutic opportunities Tobias M. Hohl Current Opinion in Infectious Diseases.2017; 30(4): 364. CrossRef
Host Soluble Mediators: Defying the Immunological Inertness of Aspergillus fumigatus Conidia Sarah Sze Wah Wong, Vishukumar Aimanianda Journal of Fungi.2017; 4(1): 3. CrossRef
Immune Recognition of Fungal Polysaccharides Brendan Snarr, Salman Qureshi, Donald Sheppard Journal of Fungi.2017; 3(3): 47. CrossRef
The Role of the Fungal Cell Wall in the Infection of Plants Ivey Geoghegan, Gero Steinberg, Sarah Gurr Trends in Microbiology.2017; 25(12): 957. CrossRef
Immunity against fungi Michail S. Lionakis, Iliyan D. Iliev, Tobias M. Hohl JCI Insight.2017;[Epub] CrossRef
Human fungal pathogens: Why should we learn? Jeong-Yoon Kim Journal of Microbiology.2016; 54(3): 145. CrossRef
Proteomic analysis of Aspergillus fumigatus – clinical implications Nicola M. Moloney, Rebecca A. Owens, Sean Doyle Expert Review of Proteomics.2016; 13(7): 635. CrossRef
How to invade a susceptible host: cellular aspects of aspergillosis Sven Krappmann Current Opinion in Microbiology.2016; 34: 136. CrossRef
The Use of Pyranoside-into-Furanoside Rearrangement and Controlled O(5) → O(6) Benzoyl Migration as the Basis of a Synthetic Strategy To Assemble (1→5)- and (1→6)-Linked Galactofuranosyl Chains Dmitry A. Argunov, Vadim B. Krylov, Nikolay E. Nifantiev Organic Letters.2016; 18(21): 5504. CrossRef
Invasive aspergillosis has emerged as one of the most common
life-threatening fungal disease of humans. The emergence
of antifungal resistant pathogens represents a current
and increasing threat to society. In turn, new strategies to
combat fungal infection are urgently required. Fungal adaptations
to stresses experienced within the human host are a
prerequisite for the survival and virulence strategies of the
pathogen. Here, we review the latest information on the
signalling pathways in Aspergillus fumigatus that contribute
to stress adaptations and virulence, while highlighting their
potential as targets for the development of novel combinational
antifungal therapies.
Citations
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Oxylipins are a class of molecules derived from the incorporation
of oxygen into polyunsaturated fatty acid substrates
through the action of oxygenases. While extensively investigated
in the context of mammalian immune responses, over
the last decade it has become apparent that oxylipins are a
common means of communication among and between plants,
animals, and fungi to control development and alter hostmicrobe
interactions. In fungi, some oxylipins are derived nonenzymatically
while others are produced by lipoxygenases,
cyclooxygenases, and monooxygenases with homology to
plant and human enzymes. Recent investigations of numerous
plant and human fungal pathogens have revealed oxylipins
to be involved in the establishment and progression of disease.
This review highlights oxylipin production by pathogenic
fungi and their role in fungal development and pathogen/
host interactions.
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Histoplasma capsulatum is a dimorphic pathogenic fungus
and causative agent of histoplasmosis, which is a respiratory
and systemic infection that is particularly severe in immunocompromised
hosts and represents the fungal homolog of
tuberculosis. In highly endemic regions, the majority of individuals
have been infected and carry the organism in a persistent
latent form that is a danger for reactivation if host
defenses are suppressed. H. capsulatum has been a model
organism for intracellular pathogenesis and fungal morphogenesis
for decades. New genomic information and application
of approaches for molecular genetic manipulation are
shedding new light on virulence mechanisms.
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