Review
Pharmacology & Pharmacy
Jie Tu, Na Liu, Yahui Huang, Wanzhen Yang, Chunquan Sheng
Summary: Candida auris is a major global threat to human health due to its strong drug resistance. This review provides a comprehensive overview of current strategies, drug candidates, and lead compounds for the treatment of C. auris. The resistance profiles and mechanisms are summarized, and the structures and activities of clinical candidates, drug combinations, antifungal chemosensitizers, repositioned drugs, new targets, and new types of compounds are discussed in detail. The review also offers perspectives for guiding future research in this field.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Chemistry, Medicinal
Martina Raschig, Bernardo Ramirez-Zavala, Johannes Wiest, Marco Saedtler, Marcus Gutmann, Ulrike Holzgrabe, Joachim Morschhauser, Lorenz Meinel
Summary: Increasing resistance to antifungal drugs poses a challenge to anti-infective therapies and contributes to mortality in infections caused by drug-resistant Candida species and strains. This study explores the use of naturally occurring molecules as lead structures for the development of new antifungal agents. The synthesized azobenzene derivatives showed inhibitory effects on both fluconazole-susceptible and fluconazole-resistant Candida species, indicating their potential therapeutic value.
ARCHIV DER PHARMAZIE
(2023)
Article
Microbiology
Yu-Shan Cheng, Jose Santinni Roma, Min Shen, Caroline Mota Fernandes, Patricia S. Tsang, He Eun Forbes, Helena Boshoff, Cristina Lazzarini, Maurizio Del Poeta, Wei Zheng, Peter R. Williamson
Summary: A bioluminescent ATP-based assay was established to identify new compounds and potential drug combinations effective against drug-resistant Candida auris. Screenings of approved drugs and pharmacologically active compounds yielded 25 compounds, including novel anti-Candida auris compounds and potential two-drug combinations that showed promising effects in vitro and in clinical isolates.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Wenkai Zhou, Xiuzhen Li, Yiqing Lin, Wei Yan, Shuling Jiang, Xiaotian Huang, Xinglong Yang, Dan Qiao, Na Li
Summary: Candida auris has emerged as a pathogenic fungus causing severe outbreaks worldwide, exhibiting high resistance rates to first-line antifungals. This study conducted a transcriptomic analysis between two isolates with different anti-drug patterns, revealing potential genes involved in drug resistance and upregulation of Hsp-related genes in the resistant strain. The study highlights novel clues for understanding the multidrug resistance mechanisms of C. auris strains.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Renato Kovacs, Fruzsina Nagy, Zoltan Toth, Lajos Forgacs, Liliana Toth, Gyorgyi Varadi, Gabor K. Toth, Karina Vadaszi, Andrew M. Borman, Laszlo Majoros, Laszlo Galgoczy
Summary: NFAP2 demonstrated synergy with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin against C. auris biofilms, indicating its strong potential as a novel antifungal compound in alternative therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Dermatology
Sanaz Aghaei Gharehbolagh, Alireza Izadi, Meysam Talebi, Fatemeh Sadeghi, Ali Zarrinnia, Fateme Zarei, Kimia Darmiani, Andrew M. Borman, Shahram Mahmoudi
Summary: This study provides an overview of drug combinations against Candida auris, showing that some combinations exhibit synergistic effects while others demonstrate antagonistic interactions. Further studies are needed to validate the potential clinical benefits of these combinations.
Article
Immunology
Jie Tu, Tianbao Zhu, Qingwen Wang, Wanzhen Yang, Yahui Huang, Defeng Xu, Na Liu, Chunquan Sheng
Summary: Candida auris is a serious public health threat that has caused a global epidemic due to its multi-drug resistance, remarkable transmissibility, and high mortality. A novel benzoanilide antifungal agent, compound A1, was discovered through a comprehensive strategy involving phenotypic screening, hit optimization, antifungal assays, and mechanism exploration. Compound A1 showed potent efficacy against Candida auris infection both in vitro and in vivo. Mechanistic investigation revealed that compound A1 inhibited the biosynthesis of virulence factors and fungal cell walls by blocking glycosylphosphatidylinositol (GPI) and GPI-anchored proteins. Therefore, compound A1 represents a promising lead compound for combating drug-resistant candidiasis.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Infectious Diseases
Zhaoxia Xu, Lei Zhang, Ran Han, Chengwei Ding, Haochang Shou, Xueguang Duan, Shengwei Zhang
Summary: This article reports a case of candidemia caused by a novel drug-resistant Candida auris strain. The strain belongs to the South Asian clade and carries the Y132F mutation in the Erg11 protein. The strain is resistant to fluconazole and amphotericin B and not susceptible to caspofungin. In addition, it exhibits multiple colony and cellular morphologies under different culture conditions.
INFECTION AND DRUG RESISTANCE
(2023)
Review
Microbiology
Helal F. Hetta, Yasmin N. Ramadan, Israa M. S. Al-Kadmy, Noura H. Abd Ellah, Lama Shbibe, Basem Battah
Summary: A multidrug-resistant pathogenic yeast called Candida auris can quickly spread among hospitalized and immunodeficient patients, causing nosocomial outbreaks and potentially pandemic outbreaks in 45 nations with high mortality rates. It has become resistant to decontamination techniques and can survive for weeks in hospitals. Nanoparticles have emerged as a promising treatment for diseases caused by this newly discovered pathogen, and are currently being researched as an effective solution against C. auris.
Article
Medicine, General & Internal
Alba Ruiz-Gaitan, Ignacio Sigona-Giangreco, Jose Manuel Perez-Royo, Victor Garcia-Bustos, Marta Garcia-Hita, Eulogio Valentin-Gomez, Salvador Giner Almaraz, Piet W. J. de Groot, Javier Peman
Summary: This study describes the morphological characteristics of C. auris colonies on three commercial chromogenic media. CHROMagar (TM) Candida Plus and HiCrome (TM) Candida can provide presumptive identification of C. auris, but identification may be difficult in the presence of mixed cultures. The use of CHROMagar (TM) Candida medium with 32 mg/L fluconazole offers better performance for the identification of C. auris by inhibiting fluconazole-susceptible strains and selecting rare or high fluconazole MIC (>32 mg/L) isolates.
Review
Dermatology
Alireza Izadi, Sanaz Aghaei Gharehbolagh, Fatemeh Sadeghi, Meysam Talebi, Kimia Darmiani, Ali Zarrinnia, Fateme Zarei, Fatemeh Peymaeei, Shaghayegh Khojasteh, Andrew M. Borman, Shahram Mahmoudi
Summary: Candida auris is a drug-resistant pathogen and finding alternative drugs through repurposing approaches would be clinically beneficial. A systematic search found several drugs/compounds that can inhibit both the planktonic and biofilm forms of C. auris.
Article
Biochemistry & Molecular Biology
Daniel Zamith-Miranda, Rafaela F. Amatuzzi, Isadora F. Munhoz da Rocha, Sharon T. Martins, Aline C. R. Lucena, Alexandre Z. Vieira, Gabriel Trentin, Fausto Almeida, Marcio L. Rodrigues, Ernesto S. Nakayasu, Joshua D. Nosanchuk, Lysangela R. Alves
Summary: Candida auris has emerged as a serious global threat due to its high resistance to conventional antifungal medications. This study treated two strains of C. auris with caspofungin and found that it caused morphological alterations, changes in cell wall composition, and upregulation of genes related to cell wall synthesis. These results provide valuable insights into the biology of C. auris and the antifungal activity of caspofungin, identifying potential cellular targets for the development of novel antifungals.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Microbiology
Samantha E. Jacobs, Jonathan L. Jacobs, Emily K. Dennis, Sarah Taimur, Meenakshi Rana, Dhruv Patel, Melissa Gitman, Gopi Patel, Sarah Schaefer, Kishore Iyer, Jang Moon, Victoria Adams, Polina Lerner, Thomas J. Walsh, YanChun Zhu, Mohammed Rokebul Anower, Mayuri M. Vaidya, Sudha Chaturvedi, Vishnu Chaturvedi
Summary: Candida auris isolates from a patient who underwent transplantation were analyzed for genome and drug resistance. The isolates showed global similarity and a distinct subcluster. Drug resistance was observed in some isolates, including those with unique mutations. The pan-drug-resistant isolates were also resistant to two-drug combination therapy. Genetic analysis revealed in-hospital evolution and circulation of the C. auris isolates.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Tatsuro Hirayama, Taiga Miyazaki, Makoto Sumiyoshi, Yuya Ito, Nobuyuki Ashizawa, Kazuaki Takeda, Naoki Iwanaga, Takahiro Takazono, Kazuko Yamamoto, Koichi Izumikawa, Katsunori Yanagihara, Koichi Makimura, Kazuhiro Tsukamoto, Shigeru Kohno, Hiroshi Mukae
Summary: Candida auris is resistant to multiple antifungal agents. This study investigated the antifungal susceptibility of C. auris and explored FKS1 mutations in isolates from mice colonized with wild-type C. auris and treated with echinocandin. Resistant isolates with FKS1 mutations were found to be micafungin- and caspofungin-resistant in vivo, but their minimum inhibitory concentrations (MICs) remained below the micafungin breakpoint in vitro.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Rita Oladele, Jessica N. Uwanibe, Idowu B. Olawoye, Abdul-Wahab O. Ettu, Jacques F. Meis, Christian T. Happi
Summary: Candida auris, a multidrug-resistant fungal pathogen, has caused severe sepsis in ICU patients in Southern Nigeria. Genetic analysis revealed antifungal resistance mutations and non-synonymous mutations in hotspot genes. These cases underscore the diagnostic gaps and the need for active disease surveillance in the region.
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
Ecology
Alexander Lorenz, Samantha J. Mpaulo
Summary: Meiosis is the underlying mechanism of Mendelian genetics, involving a specialized cell division process to generate haploid gametes with shuffling and distribution of genetic material, leading to the restoration of diploid zygotes upon fertilization. Meiotic recombination, initiated by DNA double-strand breaks (DSBs), enables the physical connection and subsequent segregation of homologous chromosomes, which forms the basis of Mendelian laws. However, the repair mechanism of meiotic DSBs also leads to genetic distortions that result in non-Mendelian processes.
Editorial Material
Biochemistry & Molecular Biology
Alexander Lorenz, Nicolas Papon
Summary: In a recent study, researchers generated genetic tools to manipulate Candida auris, providing new avenues for studying its virulence and pathogenicity.
TRENDS IN MICROBIOLOGY
(2022)
Editorial Material
Ecology
Jason B. Wolf, Anne C. Ferguson-Smith, Alexander Lorenz
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
Microbiology
Kevin Dippel, Katrin Matti, Judith Muno-Bender, Florian Michling, Silvia Brezina, Heike Semmler, Doris Rauhut, Juergen Wendland
Summary: Kveik isolates were found to be suitable for co-fermentations with certain non-conventional yeasts (NCY) to enhance beer or spirit fermentations, increasing the potential of these yeasts for beverage productions.
Article
Biochemistry & Molecular Biology
Beatrice Bernardi, Florian Michling, Juergen Froehlich, Juergen Wendland
Summary: Hybrid formation and introgressions significantly influenced the domestication of fermentative yeasts for beer, wine and cider fermentations. A comparative genomic analysis of a British cider yeast (E1) revealed introgressions of DNA from S. eubayanus and Torulaspora microellipsoides, leading to genetic modifications in various regions of the genome. These modifications resulted in improved fermentation properties, such as faster sugar consumption, higher glycerol production, and the production of fruity esters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Madina Akan, Andreas Gudiksen, Yasemin Baran, Heike Semmler, Silvia Brezina, Stefanie Fritsch, Doris Rauhut, Jurgen Wendland
Summary: This study examined the potential use of Saccharomycopsis fermentans in wine fermentations and found that selecting mutant strains resistant to the toxic compound trifluoro-leucine (TFL) can increase leucine biosynthesis and result in higher levels of isoamyl alcohol and isovalerate production during wine fermentation, thereby improving the flavor of wine.
FERMENTATION-BASEL
(2023)
Article
Biotechnology & Applied Microbiology
Jennifer Badura, Niel van Wyk, Kerstin Zimmer, Isak S. Pretorius, Christian von Wallbrunn, Juergen Wendland
Summary: This article presents a PCR-based gene targeting approach using two marker genes for directed gene manipulations in Hanseniaspora uvarum. The lack of gene-function analysis tools limits the study of this yeast, which is abundant in grapes and must. The authors developed synthetic antibiotic resistance genes as markers and successfully achieved gene replacement in H. uvarum. Although the efficiency was lower compared to Saccharomyces cerevisiae, this approach provides important tools for directed gene manipulations in H. uvarum.
FEMS YEAST RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Beatrice Bernardi, Florian Michling, Judith Muno-Bender, Katrin Matti, Juergen Wendland
Summary: This article reveals the hybrid genome of the CEG wine yeast, which is a combination of Saccharomyces cerevisiae and S. kudriavzevii. It analyzes the fermentation properties of this yeast.
FEMS YEAST RESEARCH
(2023)
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)
