Article
Microbiology
Ke-Zhi Chen, Lu-Ling Wang, Jin-Yan Liu, Jun-Tao Zhao, Si-Jia Huang, Ming-Jie Xiang
Summary: This study aimed to determine the function of Cdc50 in Candida glabrata by constructing a Delta cdc50 null mutant and its complemented strain. The results showed that loss of Cdc50 led to difficulties in yeast budding, increased cell wall integrity, enhanced drug susceptibility and weakened virulence. These findings highlight the importance of Cdc50 in C. glabrata and provide potential targets for new drug research.
Review
Chemistry, Medicinal
Hye-Won Shin, Hiroyuki Takatsu
Summary: This article reviews the current understanding of the regulatory mechanism of P4-ATPase activity and localization in mammalian cells, while also mentioning the remaining unknowns in this field.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Plant Sciences
Rosa L. Lopez-Marques, James A. Davis, Jeffrey F. Harper, Michael Palmgren
Summary: The lipid bilayer of biological membranes is complex and asymmetric, with protein P4 ATPase playing a role in generating this asymmetry. Arabidopsis contains 12 P4 ATPases, with studies confirming their essential role in basal cellular functions.
Article
Immunology
Shihao Song, Shuo Zhao, Xiuyun Sun, Lili Meng, Zijie Wang, Huihui Tan, Jingyun Liu, Min Zhang, Yinyue Deng
Summary: The compounds 5-sulfenylindole and 5-selenylindole discovered in this study showed excellent abilities to inhibit biofilm formation and hyphal formation in Candida albicans, as well as attenuating its virulence in human cell lines and mouse infection models. They also decreased the expression of genes involved in cAMP-PKA and MAPK pathways and showed synergistic effects with antifungal agents against drug-resistant strains. Additionally, 5-sulfenylindole restored the composition and richness of the intestinal microbiota in mice infected by C. albicans.
Article
Cell Biology
Selene Mogavero, Frank M. Sauer, Sascha Brunke, Stefanie Allert, Daniela Schulz, Stephanie Wisgott, Nadja Jablonowski, Osama Elshafee, Thomas Krueger, Olaf Kniemeyer, Axel A. Brakhage, Julian R. Naglik, Edward Dolk, Bernhard Hube
Summary: Candidalysin is a peptide toxin secreted by C. albicans causing epithelial damage. Specific fungal attributes are required for candidalysin delivery to host cell membranes. The toxin accumulates in invasion pockets created by invasive hyphae, as visualised using camelid nanobodies.
CELLULAR MICROBIOLOGY
(2021)
Article
Microbiology
Artyom A. Stepanov, Darya Poshvina, Alexey S. Vasilchenko
Summary: This study investigated the antifungal action of 2,4-DAPG against Candida albicans, finding that it reduced the ability of the fungus to form biofilms and inhibited its filamentation. The study also revealed an increase in Sap production and gene expression, indicating a potential mechanism of action for 2,4-DAPG.
Article
Biochemistry & Molecular Biology
Francesco Tadini-Buoninsegni, Stine A. Mikkelsen, Louise S. Mogensen, Rikke Holm, Robert S. Molday, Jens Peter Andersen
Summary: The study reveals the electrogenicity of ATP8A2 and its potential phospholipid translocation pathway involving residues with positively charged side chains.
Article
Immunology
Anais Lamy, Ewerton Macarini-Bruzaferro, Thibaud Dieudonne, Alex Peralvarez-Marin, Guillaume Lenoir, Cedric Montigny, Marc le Maire, Jose Luis Vazquez-Ibar
Summary: Gene targeting approaches have highlighted the essential role of membrane transport proteins in lipid transport and maintenance of lipid asymmetry in the malaria parasite. Specifically, ATP2 has been identified as a crucial target for potential antimalarial drugs. The study reveals that PcATP2 interacts with Plasmodium-encoded Cdc50 proteins and shows ATPase activity in the presence of phospholipids.
EMERGING MICROBES & INFECTIONS
(2021)
Article
Microbiology
Virginia E. Glazier, Juraj Kramara, Tomye Ollinger, Norma V. Solis, Robert Zarnowski, Rohan S. Wakade, Min-Ju Kim, Gabriel J. Weigel, Shen-Huan Liang, Richard J. Bennett, Melanie Wellington, David R. Andes, Mark A. Stamnes, Scott G. Filler, Damian J. Krysan, James W. Kronstad
Summary: Candida albicans, a diploid human fungal pathogen, displays significant genomic and phenotypic heterogeneity. The effect of Rob1 on biofilm and filamentation virulence traits is dependent on both the specific environmental condition and the clinical strain of C. albicans. Different alleles of Rob1 have different functional effects, with the rare ROB1(946S) allele supporting increased filamentation and biofilm formation. These findings highlight the importance of heterozygosity as a driver of C. albicans phenotypic heterogeneity.
Article
Immunology
Nichole D. Brandquist, Cierra Lampman, Elias J. Smith, Lizeth Basilio, Akram Almansob, Peter C. Iwen, Jill R. Blankenship
Summary: In this study, clinical strains of Candida albicans collected from patients with systemic infections were classified by MLST analysis. These clinical strains exhibited different filamentation patterns across various inducing conditions, indicating a broad phenotypic diversity among clinical strains. The results emphasize the importance of using diverse clinical strains in pathogenesis assays.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Microbiology
Yinhe Mao, Norma V. V. Solis, Scott G. G. Filler, Aaron P. P. Mitchell
Summary: This study found that Nrg1 plays a positive role in gene expression under hypha-inducing conditions in multiple clinical isolates, and this role is magnified in the P57055 strain. These findings indicate that strain diversity is a valuable resource for C. albicans molecular genetic analysis.
Article
Microbiology
Romain Laurian, Jade Ravent, Karine Dementhon, Marc Lemaire, Alexandre Soulard, Pascale Cotton
Summary: The survival of the pathogenic yeast Candida albicans relies on the assimilation of fermentable and non-fermentable carbon sources, particularly glucose, through the enzymatic and regulatory functions of hexokinase 2 (CaHxk2). The interaction with glucose, mediated by a conserved aspartate residue, is not only essential for enzymatic activities and glucose repression but also for filamentation and virulence in macrophages. Point mutations and deletions affecting glucose repression in Saccharomyces cerevisiae hexokinase 2 were found to be ineffective in CaHxk2, highlighting the interconnectedness of enzymatic and regulatory functions in C. albicans.
Article
Microbiology
Yen-Mu Wu, Po-Yen Huang, Yi-Chuan Cheng, Chih-Hua Lee, Meng-Chieh Hsu, Jang-Jih Lu, Shao-Hung Wang
Summary: Coinfection with Candida and Staphylococcus results in higher mortality in both patients and in vivo surrogate models. The study demonstrates that during co-biofilm formation, C. albicans and S. aureus exhibit enhanced virulence contributing to the high mortality rate observed in mixed BSIs.
Article
Multidisciplinary Sciences
Ian J. Roney, David Z. Rudner
Summary: Sorting of phospholipids between membrane bilayers is a fundamental problem, and the enzymes that catalyze phospholipid reorientation in bacteria remain unknown. Members of the DedA superfamily have been implicated in lipid carrier transport and lipid scrambling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Aneta K. Urbanek, Jakub Muraszko, Daria Derkacz, Marcin Lukaszewicz, Przemyslaw Bernat, Anna Krasowska
Summary: The opportunistic pathogen Candida albicans causes systemic infections. Due to the increasing drug resistance, currently used antifungal drugs are insufficient. One of the resistance mechanisms is increased expression of plasma membrane transporters and decreased sphingolipid content. Using svFCS technique, CaCdr1p is found to localize in detergent resistant microdomains. Inhibition of sphingolipid synthesis leads to increased sensitivity in C. albicans erg11 Delta/Delta strain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Bhawik Kumar Jain, Roma Dahara, Dibyendu Bhattacharyya
JOURNAL OF CELL SCIENCE
(2019)
Article
Microbiology
Tian Chen, Andrew S. Wagner, Robert N. Tams, James E. Eyer, Sarah J. Kauffman, Eric R. Gann, Elias J. Fernandez, Todd B. Reynolds
Article
Immunology
Robert N. Tams, Andrew S. Wagner, Joseph W. Jackson, Eric R. Gann, Timothy E. Sparer, Todd B. Reynolds
INFECTION AND IMMUNITY
(2020)
Article
Cell Biology
Sudeshna Roy Chowdhury, Chumki Bhattacharjee, Jason C. Caser, Bhawik Kumar Jain, Benjamin S. Glick, Dibyendu Bhattacharyya
JOURNAL OF CELL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Bhawik Kumar Jain, Bartholomew P. Roland, Todd R. Graham
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biology
Lin Bai, Qinglong You, Bhawik K. Jain, H. Diessel Duan, Amanda Kovach, Todd R. Graham, Huilin Li
Article
Microbiology
Andrew S. Wagner, Trevor J. Hancock, Stephen W. Lumsdaine, Sarah J. Kauffman, Mikayla M. Mangrum, Elise K. Phillips, Timothy E. Sparer, Todd B. Reynolds
Summary: Activation of the Cek1 MAPK pathway and unmasking of immunogenic cell wall epitope ss(1,3)-glucan by specific genetic mutations weaken the virulence of Candida albicans. Neutrophils play a critical role in the clearance of unmasked fungal cells.
Article
Multidisciplinary Sciences
Lin Bai, Bhawik K. Jain, Qinglong You, H. Diessel Duan, Mehmet Takar, Todd R. Graham, Huilin Li
Summary: This study reports the structure of the P4B ATPase Neo1 in several states, clarifying its substrate transport mechanism and revealing similar functional intermediate states to dimeric flippases. The findings suggest that evolutionarily distant P4 ATPases use a structurally conserved mechanism for substrate transport.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Naini Chakraborty, Bhawik Kumar Jain, Samruddhi Shembekar, Dibyendu Bhattacharyya
Summary: This study investigates the potential functional link between ER-mitochondria encounter structures (ERMES) and ER exit sites (ERES). The disruption of either ERMES or ERES affects the other, and a chaperone protein, Djp1, is found to regulate mitochondrial protein import in the ERES-ERMES proximal region.
Article
Genetics & Heredity
Andrew S. Wagner, Stephen W. Lumsdaine, Mikayla M. Mangrum, Ainsley E. King, Trevor J. Hancock, Timothy E. Sparer, Todd B. Reynolds
Summary: The fungal pathogen Candida albicans regulates the exposure of the antigen beta(1,3)-glucan to the host immune system through masking or unmasking. The phosphatase calcineurin plays a key role in mediating the unmasking of beta(1,3)-glucan in response to specific signals. The loss of genes involved in unmasking attenuate the virulence of C. albicans.
Article
Immunology
Andrew S. Wagner, Amanda K. Vogel, Stephen W. Lumsdaine, Elise K. Phillips, Hubertine M. E. Willems, Brian M. Peters, Todd B. Reynolds
Summary: This study investigates the impact of beta(1, 3)-glucan unmasking on the progression of two manifestations of candidiasis: oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). The results show that increased unmasking attenuates fungal burden and prolongs survival in systemic infection. However, in OPC, selection for suppressor mutants that no longer display increased unmasking occurs, leading to restoration of fungal burden trends. In VVC, unmasked cells increase recruitment of polymorphonuclear cells and interleukin-1beta levels within the vaginal lumen. These findings suggest a niche-specific impact of unmasking on disease progression.
INFECTION AND IMMUNITY
(2022)
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.
Review
Mycology
Tian Chen, Andrew S. Wagner, Todd B. Reynolds
Summary: The exposure of (1,3)-glucan plays a crucial role in anti-fungal immunity, and changes in the levels of surface exposed (1,3)-glucan can be induced by environmental stimuli and stressors within the host. Understanding the signal transduction cascades that regulate the changes in (1,3)-glucan exposure is critical for future therapeutic development.
FRONTIERS IN FUNGAL BIOLOGY
(2022)