Article
Biotechnology & Applied Microbiology
Mi-Jin Kim, Bong Hyun Sung, Hyun-Jin Kim, Jung-Hoon Sohn, Jung-Hoon Bae
Summary: Protein expression with a fusion partner followed by the removal of the fusion partner via in vitro processing with a specific endoprotease is a favored method for efficient production of intact recombinant proteins. This study developed an autolysis-proof Kex2p endoprotease, facilitating the large-scale production of recombinant proteins.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biology
Rohan S. Wakade, Laura C. Ristow, Melanie Wellington, Damian J. Krysan
Summary: Candida albicans, a common human fungal pathogen, undergoes a morphogenetic transition from yeast to filamentous forms during infection. In this study, the authors used intravital imaging assays to screen transcription factor mutants in a mouse model and identified regulators of filament initiation and elongation. They found distinct sets of transcription factors that affect these processes in vivo, including some that have no effect in vitro. Furthermore, they discovered a new mode of function for the widely studied transcription factor Efg1 in mediating relief of Nrg1 repression. This study provides the first characterization of the transcriptional network governing C. albicans filamentation in vivo.
Article
Microbiology
Yoshihiro Ojima, Naoki Yokota, Yuki Tanibata, Shinsuke Nerome, Masayuki Azuma
Summary: This study investigated the mechanism of toxicity of Toyocamycin (TM) and its analogs to Candida albicans. It was found that the absence of purine nucleoside transport activity from Saccharomyces cerevisiae (S. cerevisiae) made it less susceptible to TM and its analogs. However, when the concentrative nucleoside transporter (CNT) of Candida albicans (C. albicans) was expressed in S. cerevisiae, the sensitivity to TM and its analogs was restored. In addition, introducing human CNT3 into S. cerevisiae also made it sensitive to TM and its analogs. These findings enhance our understanding of the mechanisms of action of adenosine analogs toward Candida pathogens and human cells.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemistry & Molecular Biology
Louis A. Chevalier, Mario Pinar, Remi Le Borgne, Catherine Durieu, Miguel Penalva, Arezki Boudaoud, Nicolas Minc
Summary: Hyphal tip growth in filamentous fungi is driven by the expansion of a protective cell wall (CW) secreted from apical vesicles. We found that tip growth is associated with balanced rates of CW secretion and expansion, and affecting this balance leads to immediate changes in CW thickness, mechanics, and shape. These findings provide unprecedented insights into the dynamics of CW secretion and expansion, and their role in stabilizing fungal tip growth and promoting morphogenetic plasticity.
Article
Multidisciplinary Sciences
Mohammad Tahseen A. L. Bataineh, Nelson Cruz Soares, Mohammad Harb Semreen, Stefano Cacciatore, Nihar Ranjan Dash, Mohamad Hamad, Muath Khairi Mousa, Jasmin Shafarin Abdul Salam, Mutaz F. Al Gharaibeh, Luiz F. Zerbini, Mawieh Hamad
Summary: This study characterized the role of Ppg1 in regulating filament formation, metabolism, and virulence in Candida albicans through RNA sequencing and metabolomics analysis. The ppg1 Delta/Delta strain exhibited significant changes in gene expression and metabolite enrichment, highlighting the link between filamentation and metabolism in the pathogen.
Article
Multidisciplinary Sciences
Xin Li, Irina Leonardi, Gregory G. Putzel, Alexa Semon, William D. Fiers, Takato Kusakabe, Woan-Yu Lin, Iris H. Gao, Itai Doron, Alejandra Gutierrez-Guerrero, Meghan B. DeCelie, Guilhermina M. Carriche, Marissa Mesko, Chen Yang, Julian R. Naglik, Bernhard Hube, Ellen J. Scherl, Iliyan D. Iliev
Summary: The study reveals the rich genetic diversity of pathogenic Candida albicans strains in the colonic mucosa of patients with inflammatory bowel disease, with some strains having high immune-cell-damaging capacity (HD strains). These strains exacerbate intestinal inflammation in vivo through specific mechanisms, highlighting new insights into host-fungal interactions and potential diagnostic and therapeutic targets for inflammatory diseases.
Article
Physiology
Cory H. T. Boone, Kory A. Parker, Daniel J. Gutzmann, Audrey L. Atkin, Kenneth W. Nickerson
Summary: This study investigates the sensitivity of different ploidy and mating type locus (MTL) to farnesol, and proposes that differentially regulated mechanisms of entry and efflux determine the cellular concentration of farnesol. These mechanisms involve various physiological functions, including MTL type, ubiquinone type, energy availability, and aerobic/anaerobic status.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Genetics & Heredity
Pengjie Hu, Hao Ding, Lan Shen, Guang-Jun He, Huimin Liu, Xiuyun Tian, Changyu Tao, Xiangzheng Bai, Jingnan Liang, Cheng Jin, Xinping Xu, Ence Yang, Linqi Wang
Summary: The study found that GlcN specifically induces a unique hyperactive cell wall synthetic response in Cryptococcus, which determines the key event of GlcN-induced filamentation (GIF). The Mpk1-directed cell wall signaling pathway connects the cell wall synthetic response and GIF activation in different Cryptococcus pathogens. These results reveal a previously unrecognized function of GlcN in stimulating cell wall signaling and biosynthetic machinery, providing a unique dimorphism commitment mechanism underlying the signal specificity of the yeast-to-hypha transition in Cryptococcus pathogens.
Article
Microbiology
Gordon Williamson, Ana Sofia Brito, Adriana Bizior, Giulia Tamburrino, Gaetan Dias Mirandela, Thomas Harris, Paul A. Hoskisson, Ulrich Zachariae, Anna Maria Marini, Melanie Boeckstaens, Arnaud Javelle
Summary: Fungal infections pose a significant threat to human health and crop yields. This study reveals that variations in the Twin-His motif of Amt-Mep-Rh transporters trigger a mechanistic switch from a specific transporter to an unspecific ion channel. These findings support a transport mechanism-driven signaling process in fungal filamentation induction.
Article
Microbiology
Yasmin Ahmed, Melanie A. C. Ikeh, Donna M. MacCallum, Alison M. Day, Kevin Waldron, Janet Quinn
Summary: Polyphosphate mobilization plays a vital role in the pathobiology of Candida albicans, impacting processes such as activation of the Pho4 transcription factor, cell cycle progression, stress resistance, morphogenetic switching, and virulence. Blocking polyphosphate mobilization leads to significant morphological defects and attenuated virulence.
Review
Biotechnology & Applied Microbiology
Gabriela Fior Ribeiro, Eszter Denes, Helen Heaney, Delma S. Childers
Summary: Studies have discovered mechanisms of antifungal resistance and tolerance in Candida species, and 'Omics technologies provide insights into cellular responses to antifungal therapy. These findings help understand physiological changes that influence fungal survival in the host and during antifungal challenges.
FEMS YEAST RESEARCH
(2021)
Article
Multidisciplinary Sciences
Jakub Suchodolski, Daria Derkacz, Przemyslaw Bernat, Anna Krasowska
Summary: The study evaluated the effect of capric acid produced by probiotic yeast Saccharomyces boulardii on the activities of fluconazole and amphotericin B against pathogenic Candida albicans fungus. The results showed that capric acid may be a promising additive in combination with fluconazole, reducing efflux activity of multidrug resistance transporter Cdr1p. However, capric acid alone stimulated ergosterol production in C. albicans, leading to cross resistance towards amphotericin B. It is concluded that amphotericin B should not be administered with dietary supplements containing capric acid or S. boulardii cells.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Gabriela Rios Martini, Ekaterina Tikhonova, Elisa Rosati, Meghan Bialt Decelie, Laura Katharina Sievers, Florian Tran, Matthias Lessing, Arne Bergfeld, Sophia Hinz, Susanna Nikolaus, Julia Kuempers, Anna Matysiak, Philipp Hofmann, Carina Saggau, Stephan Schneiders, Ann-Kristin Kamps, Gunnar Jacobs, Wolfgang Lieb, Jochen Maul, Britta Siegmund, Barbara Seegers, Holger Hinrichsen, Hans-Heinrich Oberg, Daniela Wesch, Stefan Bereswill, Markus M. Heimesaat, Jan Rupp, Olaf Kniemeyer, Axel A. Brakhage, Sascha Brunke, Bernhard Hube, Konrad Aden, Andre Franke, Iliyan D. Iliev, Alexander Scheffold, Stefan Schreiber, Petra Bacher
Summary: Aberrant CD4(+) T cell reactivity against intestinal microorganisms is thought to drive mucosal inflammation in inflammatory bowel diseases. This study identifies yeasts as direct activators of altered CD4(+) T cell reactions in patients with Crohn's disease, revealing their potential role in chronic activation of inflammatory immune responses.
Article
Biochemistry & Molecular Biology
Vadim B. Krylov, Anton N. Kuznetsov, Alina V. Polyanskaya, Pavel V. Tsarapaev, Dmitry V. Yashunsky, Nikolay E. Kushlinskii, Nikolay E. Nifantiev
Summary: The study analyzed the levels of IgG antibodies in the sera of healthy donors and patients with colorectal cancer using synthetic oligosaccharides related to different fragments of fungal mannan. The findings showed that variations in the oligosaccharide structure significantly modified the binding ability of ligands to circulating antibodies. The study highlighted the importance of ligand surface presentation density in enzyme immunoassay results.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Microbiology
Matthew R. Breuer, Ananya Dasgupta, Joseph G. Vasselli, Xiaorong Lin, Brian D. Shaw, Matthew S. Sachs
Summary: The prevalence and increasing incidence of fungal infections globally is a significant worldwide health problem. Cryptococcosis, primarily caused by the pathogenic yeast Cryptococcus neoformans, is responsible for approximatelyestimated deaths annually. The scarcity of treatments and the increasing resistance to current therapeutics highlight the need for the development of antifungal agents which have novel mechanisms of action and are suitable for clinical use. Repurposing existing FDA-approved compounds as antimycotic therapeutics is a promising strategy for the rapid development of such new treatments. Sertraline (SRT), a commonly prescribed antidepressant, is a broad-spectrum antifungal agent with particular efficacy against C. neoformans. However, the effect of SRT on fungal physiology is not understood. Here, we report that SRT induces the formation of supersized lipid droplets (SLDs) in C. neoformans, and in Candida albicans, Saccharomyces cerevisiae, and Aspergillus fumigatus. SLDs were not induced in C. neoformans by treatment with the antifungal fluconazole (FLC), consistent with SRT and FLC acting differently to perturb C. neoformans physiology. The formation of SLDs in response to SRT indicates that this compound alters the lipid metabolism of C. neoformans. Moreover, the SRT-induced enlargement of LDs in other fungal species may indicate a common fungal response to SRT.
Review
Multidisciplinary Sciences
Jennifer Geddes-McAlister, Rebecca S. Shapiro
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2019)
Article
Biochemical Research Methods
Viola Halder, Caroline B. M. Porter, Alejandro Chavez, Rebecca S. Shapiro
Article
Microbiology
Lauren Wensing, Jehoshua Sharma, Deeva Uthayakumar, Yannic Proteau, Alejandro Chavez, Rebecca S. Shapiro
Correction
Biochemical Research Methods
Viola Halder, Caroline B. M. Porter, Alejandro Chavez, Rebecca S. Shapiro
Article
Microbiology
Yikun Mei, Tong Jiang, Yun Zou, Yuanyuan Wang, Jia Zhou, Jinyang Li, Lin Liu, Jingcong Tan, Luqi Wei, Jingquan Li, Huanqin Dai, Yibing Peng, Lixin Zhang, Jose L. Lopez-Ribot, Rebecca S. Shapiro, Changbin Chen, Ning-Ning Liu, Hui Wang
FRONTIERS IN MICROBIOLOGY
(2020)
Review
Microbiology
Viola Halder, Brianna McDonnell, Deeva Uthayakumar, Jane Usher, Rebecca S. Shapiro
Summary: Genetic interaction (GI) analysis is a powerful genetic strategy used to dissect epistatic interactions between genes by analyzing the fitness and phenotypes of mutant cells. It has been applied in diverse microbial pathogens to study virulence, antimicrobial drug resistance, and host-pathogen interactions, providing important insights into complex genetic networks.
FEMS MICROBIOLOGY REVIEWS
(2021)
News Item
Biochemistry & Molecular Biology
Jehoshua Sharma, Rebecca S. Shapiro
Summary: Research investigates the biochemical mechanism behind the inhibition of virulence in the fungal pathogen Candida albicans by mucus glycans.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Microbiology
Emily Puumala, Olga Zaslaver, Amy Chen, Dustin Duncan, Meea Fogal, Rebecca S. Shapiro, Mohammad T. Mazhab-Jafari, Luke Whitesell, J. Rafael Montenegro-Burke, Nicole Robbins, Leah E. Cowen
Summary: Candida species, including Candida auris, are becoming increasingly resistant to antifungal drugs. In this study, researchers identified a compound called MMV688766 from a drug library that displayed potent fungicidal activity against C. auris and other fungal pathogens. They discovered that MMV688766 disrupts cellular lipid homeostasis, leading to a decrease in certain lipid intermediates and fatty acids and an increase in lysophospholipids. Further experiments revealed that the loss of a transcriptional regulator called HAL9 confers resistance to MMV688766, suggesting a novel stress response mechanism in fungi. These findings highlight the importance of targeting lipid homeostasis to combat drug-resistant fungal infections.
Article
Multidisciplinary Sciences
Alyssa Ann La Bella, Marissa Jeme Andersen, Nicholas C. Gervais, Jonathan Jesus Molina, Alex Molesan, Peter V. Stuckey, Lauren Wensing, Clarissa J. Nobile, Rebecca S. Shapiro, Felipe Hiram Santiago-Tirado, Ana Lidia Flores-Mireles
Summary: Catheter-associated urinary tract infections (CAUTIs) are a common type of hospital-acquired infection, accounting for 40% of cases. However, little is known about how fungal CAUTIs are established. This study reveals that the catheterized bladder environment induces biofilm formation, dependent on Efg1 and fibrinogen (Fg), which leads to CAUTI. The adhesin Als1 is identified as a critical factor for fungal biofilm formation. The findings provide insights into the mechanisms of fungal CAUTI establishment and may contribute to the development of new preventive therapies.
Article
Microbiology
Brooke Rathie, Bart Theelen, Martin Laurence, Rebecca S. Shapiro
Summary: This study tested the efficacy of four antifungal drugs against three Malassezia species, finding new drugs isavuconazole and artemisinin with antifungal properties. Itraconazole was found most effective against Malassezia. This research is important for identifying effective antifungal therapies.
MICROBIOLOGY SPECTRUM
(2023)
Editorial Material
Microbiology
Rebecca S. Shapiro
NATURE REVIEWS MICROBIOLOGY
(2023)
Editorial Material
Microbiology
Rebecca S. Shapiro, Aleeza C. Gerstein
Summary: Fungal pathogens pose a significant infectious disease challenge, and combination therapy using adjuvants shows potential in enhancing the efficacy of antifungal drugs. Recent research has identified 1,4-benzodiazepines as promising molecules to enhance the activity of azole drugs against Candida spp. These molecules exhibited potentiation of fluconazole, increased fungicidal activity, inhibited filamentation, and improved host survival. This study contributes to the important goal of reducing mortality due to antimicrobial resistance.
Article
Biotechnology & Applied Microbiology
Nicholas C. Gervais, Viola Halder, Rebecca S. Shapiro
Summary: Functional genomic screening of genetic mutant libraries has been conducted to characterize gene function in diverse organisms, including the fungal pathogen Candida albicans. Compilation and organization of screening data from approximately 400 screens has led to the creation of a genetic mutant strain database for quantitative and comparative analysis, providing valuable insight into this critical fungal pathogen.
FEMS YEAST RESEARCH
(2021)
Article
Genetics & Heredity
Sierra Rosiana, Liyang Zhang, Grace H. Kim, Alexey Revtovich, Deeva Uthayakumar, Arjun Sukumaran, Jennifer Geddes-McAlister, Natalia Kirienko, Rebecca S. Shapiro
Summary: This study utilized a CRISPR-based platform to construct a library of Candida albicans adhesin mutants, and identified key roles of adhesin proteins in fungal virulence through high-throughput screening using a Caenorhabditis elegans host system. In vitro analyses showed the importance of adhesins in cellular morphogenesis, biofilm formation, and host colonization. Genetic interaction analysis revealed novel significant negative interactions, highlighting the complex role of adhesins in mediating virulence of this fungal pathogen.
Review
Microbiology
Jehoshua Sharma, Sierra Rosiana, Iqra Razzaq, Rebecca S. Shapiro
