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  1. Article ; Online: Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection.

    Bing, Jian / Guan, Zhangyue / Zheng, Tianhong / Ennis, Craig L / Nobile, Clarissa J / Chen, Changbin / Chu, Haiqing / Huang, Guanghua

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2381

    Abstract: Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in ... ...

    Abstract Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.
    MeSH term(s) Animals ; Mice ; Candida/genetics ; Candidiasis/microbiology ; Candida auris ; Saccharomyces cerevisiae ; Phenotype ; Sepsis ; Antifungal Agents ; Microbial Sensitivity Tests ; Mammals
    Chemical Substances Antifungal Agents
    Language English
    Publishing date 2024-03-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46786-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4.

    Bing, Jian / Guan, Zhangyue / Zheng, Tianhong / Zhang, Zhijie / Fan, Shuru / Ennis, Craig L / Nobile, Clarissa J / Huang, Guanghua

    PLoS pathogens

    2023  Volume 19, Issue 3, Page(s) e1011239

    Abstract: Candida auris is an emerging multidrug-resistant fungal pathogen and a new global threat to human health. A unique morphological feature of this fungus is its multicellular aggregating phenotype, which has been thought to be associated with defects in ... ...

    Abstract Candida auris is an emerging multidrug-resistant fungal pathogen and a new global threat to human health. A unique morphological feature of this fungus is its multicellular aggregating phenotype, which has been thought to be associated with defects in cell division. In this study, we report a new aggregating form of two clinical C. auris isolates with increased biofilm forming capacity due to enhanced adherence of adjacent cells and surfaces. Unlike the previously reported aggregating morphology, this new aggregating multicellular form of C. auris can become unicellular after treatment with proteinase K or trypsin. Genomic analysis demonstrated that amplification of the subtelomeric adhesin gene ALS4 is the reason behind the strain's enhanced adherence and biofilm forming capacities. Many clinical isolates of C. auris have variable copy numbers of ALS4, suggesting that this subtelomeric region exhibits instability. Global transcriptional profiling and quantitative real-time PCR assays indicated that genomic amplification of ALS4 results in a dramatic increase in overall levels of transcription. Compared to the previously characterized nonaggregative/yeast-form and aggregative-form strains of C. auris, this new Als4-mediated aggregative-form strain of C. auris displays several unique characteristics in terms of its biofilm formation, surface colonization, and virulence.
    MeSH term(s) Humans ; Candida/genetics ; Antifungal Agents ; Candida auris ; Biofilms ; Genomics ; Microbial Sensitivity Tests
    Chemical Substances Antifungal Agents
    Language English
    Publishing date 2023-03-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011239
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Candida albicans MTLa2 regulates the mating response through both the a-factor and α-factor sensing pathways

    Li, Chao / Tao, Li / Guan, Zhangyue / Hu, Tianren / Wang, Sijia / Liang, Weihong / Zhao, Fei / Huang, Guanghua

    Fungal genetics and biology. 2022 Apr., v. 159

    2022  

    Abstract: The diploid fungal pathogen Candida albicans has three configurations at the mating type locus (MTL): heterozygous (a/α) and homozygous (a/a or α/α). C. albicans MTL locus encodes four transcriptional regulators (MTLa1, a2, α1, and α2). The conserved a1/ ... ...

    Abstract The diploid fungal pathogen Candida albicans has three configurations at the mating type locus (MTL): heterozygous (a/α) and homozygous (a/a or α/α). C. albicans MTL locus encodes four transcriptional regulators (MTLa1, a2, α1, and α2). The conserved a1/α2 heterodimer controls not only mating competency but also white-opaque heritable phenotypic switching. However, the regulatory roles of MTLa2 and α1 are more complex and remain to be investigated. MTLa/a cells often express a cell type-specific genes and mate as the a-type partner, whereas MTLα/α cells express α-specific genes and mate as the α-type partner. In this study, we report that the MTLa2 regulator controls the formation of mating projections through both the a- and α-pheromone-sensing pathways and thus results in the bi-mater feature of “α cells” of C. albicans. Ectopic expression of MTLa2 in opaque α cells activates the expression of not only MFA1 and STE3 (a-pheromone receptor) but also MFα1 and STE2 (α-pheromone receptor). Inactivation of either the MFa-Ste3 or MFα-Ste2 pheromone-sensing pathway cannot block the MTLa2-induced development of mating projections. However, the case is different in MTLα1-ectopically expressed opaque a cells. Inactivation of the MFα-Ste2 but not the MFa-Ste3 pheromone-sensing pathway blocks MTLα1-induced development of mating projections. Therefore, MTLa2 and MTLα1 exhibit distinct regulatory features that control the mating response in C. albicans. These findings shed new light on the regulatory mechanism of bi-mating behaviors and sexual reproduction in C. albicans.
    Keywords Candida albicans ; diploidy ; fungi ; heterozygosity ; homozygosity ; loci ; microbial genetics ; pathogens ; phenotype ; sexual reproduction ; transcription (genetics)
    Language English
    Dates of publication 2022-04
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1319820-8
    ISSN 1096-0937 ; 1087-1845 ; 0147-5975
    ISSN (online) 1096-0937
    ISSN 1087-1845 ; 0147-5975
    DOI 10.1016/j.fgb.2022.103664
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    In stock of ZB MED Bonn / Germany

    Z 79/730: Show issues

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  4. Article ; Online: Candida albicans MTLa2 regulates the mating response through both the a-factor and α-factor sensing pathways.

    Li, Chao / Tao, Li / Guan, Zhangyue / Hu, Tianren / Wang, Sijia / Liang, Weihong / Zhao, Fei / Huang, Guanghua

    Fungal genetics and biology : FG & B

    2022  Volume 159, Page(s) 103664

    Abstract: The diploid fungal pathogen Candida albicans has three configurations at the mating type locus (MTL): heterozygous (a/α) and homozygous (a/a or α/α). C. albicans MTL locus encodes four transcriptional regulators (MTLa1, a2, α1, and α2). The conserved a1/ ... ...

    Abstract The diploid fungal pathogen Candida albicans has three configurations at the mating type locus (MTL): heterozygous (a/α) and homozygous (a/a or α/α). C. albicans MTL locus encodes four transcriptional regulators (MTLa1, a2, α1, and α2). The conserved a1/α2 heterodimer controls not only mating competency but also white-opaque heritable phenotypic switching. However, the regulatory roles of MTLa2 and α1 are more complex and remain to be investigated. MTLa/a cells often express a cell type-specific genes and mate as the a-type partner, whereas MTLα/α cells express α-specific genes and mate as the α-type partner. In this study, we report that the MTLa2 regulator controls the formation of mating projections through both the a- and α-pheromone-sensing pathways and thus results in the bi-mater feature of "α cells" of C. albicans. Ectopic expression of MTLa2 in opaque α cells activates the expression of not only MFA1 and STE3 (a-pheromone receptor) but also MFα1 and STE2 (α-pheromone receptor). Inactivation of either the MFa-Ste3 or MFα-Ste2 pheromone-sensing pathway cannot block the MTLa2-induced development of mating projections. However, the case is different in MTLα1-ectopically expressed opaque a cells. Inactivation of the MFα-Ste2 but not the MFa-Ste3 pheromone-sensing pathway blocks MTLα1-induced development of mating projections. Therefore, MTLa2 and MTLα1 exhibit distinct regulatory features that control the mating response in C. albicans. These findings shed new light on the regulatory mechanism of bi-mating behaviors and sexual reproduction in C. albicans.
    MeSH term(s) Candida albicans/metabolism ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Gene Expression Regulation, Fungal/genetics ; Genes, Mating Type, Fungal/genetics ; Pheromones/genetics ; Receptors, Pheromone/genetics ; Receptors, Pheromone/metabolism ; Reproduction
    Chemical Substances Fungal Proteins ; Pheromones ; Receptors, Pheromone
    Language English
    Publishing date 2022-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1319820-8
    ISSN 1096-0937 ; 1087-1845 ; 0147-5975
    ISSN (online) 1096-0937
    ISSN 1087-1845 ; 0147-5975
    DOI 10.1016/j.fgb.2022.103664
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2431: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
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  5. Article ; Online: Hotspot mutations and genomic expansion of ERG11 are major mechanisms of azole resistance in environmental and human commensal isolates of Candida tropicalis.

    Hu, Tianren / Wang, Sijia / Bing, Jian / Zheng, Qiushi / Du, Han / Li, Chao / Guan, Zhangyue / Bai, Feng-Yan / Nobile, Clarissa J / Chu, Haiqing / Huang, Guanghua

    International journal of antimicrobial agents

    2023  Volume 62, Issue 6, Page(s) 107010

    Abstract: Objectives: Infections caused by azole-resistant Candida tropicalis strains are increasing in clinical settings. The reason for this epidemical change and the mechanisms of C. tropicalis azole resistance are not fully understood.: Methods: In this ... ...

    Abstract Objectives: Infections caused by azole-resistant Candida tropicalis strains are increasing in clinical settings. The reason for this epidemical change and the mechanisms of C. tropicalis azole resistance are not fully understood.
    Methods: In this study, we performed biological and genomic analyses of 239 C. tropicalis strains, including 115 environmental and 124 human commensal isolates.
    Results: Most (99.2%) of the isolates had a baseline diploid genome. The strains from both environmental and human niches exhibit similar abilities to survive under stressful conditions and produce secreted aspartic proteases. However, the human commensal isolates exhibited a stronger ability to filament than the environmental strains. We found that 19 environmental isolates (16.5%) and 24 human commensal isolates (19.4%) were resistant to fluconazole. Of the fluconazole-resistant strains, 37 isolates (86.0%) also exhibited cross-resistance to voriconazole. Whole-genome sequencing and phylogenetic analyses revealed that both environmental and commensal isolates were widely distributed in a number of genetic clusters, but the two populations exhibited a close genetic association. The majority of fluconazole-resistant isolates were clustered within a single clade (X).
    Conclusions: The combination of hotspot mutations (Y132F and S154F) and genomic expansion of ERG11, which encodes the azole target lanosterol 14-α-demethylase and represents a major target of azole drugs, was a major mechanism for the development of azole resistance. The isolates carrying both hotspot mutations and genomic expansion of ERG11 exhibited cross-resistance to fluconazole and voriconazole. Moreover, the azole-resistant isolates from both the environmental and human commensal niches showed similar genotypes.
    MeSH term(s) Humans ; Antifungal Agents/pharmacology ; Antifungal Agents/therapeutic use ; Azoles/pharmacology ; Candida tropicalis/genetics ; Drug Resistance, Fungal/genetics ; Fluconazole/pharmacology ; Fungal Proteins/genetics ; Genomics ; Microbial Sensitivity Tests ; Mutation ; Phylogeny ; Voriconazole/pharmacology
    Chemical Substances Antifungal Agents ; Azoles ; Fluconazole (8VZV102JFY) ; Fungal Proteins ; Voriconazole (JFU09I87TR)
    Language English
    Publishing date 2023-10-18
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1093977-5
    ISSN 1872-7913 ; 0924-8579
    ISSN (online) 1872-7913
    ISSN 0924-8579
    DOI 10.1016/j.ijantimicag.2023.107010
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3368: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 500: Show issues

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  6. Article ; Online: Atmospheric humidity regulates same-sex mating in Candida albicans through the trehalose and osmotic signaling pathways.

    Li, Chao / Tao, Li / Guan, Guobo / Guan, Zhangyue / Perry, Austin M / Hu, Tianren / Bing, Jian / Xu, Ming / Nobile, Clarissa J / Huang, Guanghua

    Science China. Life sciences

    2023  Volume 66, Issue 8, Page(s) 1915–1929

    Abstract: Sexual reproduction is prevalent in eukaryotic organisms and plays a critical role in the evolution of new traits and in the generation of genetic diversity. Environmental factors often have a direct impact on the occurrence and frequency of sexual ... ...

    Abstract Sexual reproduction is prevalent in eukaryotic organisms and plays a critical role in the evolution of new traits and in the generation of genetic diversity. Environmental factors often have a direct impact on the occurrence and frequency of sexual reproduction in fungi. The regulatory effects of atmospheric relative humidity (RH) on sexual reproduction and pathogenesis in plant fungal pathogens and in soil fungi have been extensively investigated. However, the knowledge of how RH regulates the lifecycles of human fungal pathogens is limited. In this study, we report that low atmospheric RH promotes the development of mating projections and same-sex (homothallic) mating in the human fungal pathogen Candida albicans. Low RH causes water loss in C. albicans cells, which results in osmotic stress and the generation of intracellular reactive oxygen species (ROS) and trehalose. The water transporting aquaporin Aqy1, and the G-protein coupled receptor Gpr1 function as cell surface sensors of changes in atmospheric humidity. Perturbation of the trehalose metabolic pathway by inactivating trehalose synthase or trehalase promotes same-sex mating in C. albicans by increasing osmotic or ROS stresses, respectively. Intracellular trehalose and ROS signal the Hog1-osmotic and Hsf1-Hsp90 signaling pathways to regulate the mating response. We, therefore, propose that the cell surface sensors Aqy1 and Gpr1, intracellular trehalose and ROS, and the Hog1-osmotic and Hsf1-Hsp90 signaling pathways function coordinately to regulate sexual mating in response to low atmospheric RH conditions in C. albicans.
    MeSH term(s) Humans ; Candida albicans/genetics ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Trehalose/metabolism ; Humidity ; Reactive Oxygen Species/metabolism ; Signal Transduction/physiology ; Reproduction/physiology
    Chemical Substances Fungal Proteins ; Trehalose (B8WCK70T7I) ; Reactive Oxygen Species
    Language English
    Publishing date 2023-04-11
    Publishing country China
    Document type Journal Article
    ZDB-ID 2546732-3
    ISSN 1869-1889 ; 1674-7305
    ISSN (online) 1869-1889
    ISSN 1674-7305
    DOI 10.1007/s11427-023-2309-1
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