Pub Date : 2023-06-01DOI: 10.1007/s00294-023-01262-6
Julia Lettow, Felix Kliewe, Rasha Aref, Hans-Joachim Schüller
Transcriptional corepressors Sin3, Cyc8 and Tup1 are important for downregulation of gene expression by recruiting various histone deacetylases once they gain access to defined genomic locations by interaction with pathway-specific repressor proteins. In this work we systematically investigated whether 17 yeast repressor proteins (Cti6, Dal80, Fkh1, Gal80, Mig1, Mot3, Nrg1, Opi1, Rdr1, Rox1, Sko1, Ume6, Ure2, Xbp1, Yhp1, Yox1 and Whi5) representing several unrelated regulatory pathways are able to bind to Sin3, Cyc8 and Tup1. Our results show that paired amphipathic helices 1 and 2 (PAH1 and PAH2) of Sin3 are functionally redundant for some regulatory pathways. WD40 domains of Tup1 proved to be sufficient for interaction with repressor proteins. Using length variants of selected repressors, we mapped corepressor interaction domains (CIDs) in vitro and assayed gene repression in vivo. Systematic comparison of CID minimal sequences allowed us to define several related positional patterns of hydrophobic amino acids some of which could be confirmed as functionally supported by site-directed mutagenesis. Although structural predictions indicated that certain CIDs may be α-helical, most repression domains appear to be randomly structured and must be considered as intrinsically disordered regions (IDR) adopting a defined conformation only by interaction with a corepressor.
{"title":"Functional characterization and comparative analysis of gene repression-mediating domains interacting with yeast pleiotropic corepressors Sin3, Cyc8 and Tup1.","authors":"Julia Lettow, Felix Kliewe, Rasha Aref, Hans-Joachim Schüller","doi":"10.1007/s00294-023-01262-6","DOIUrl":"https://doi.org/10.1007/s00294-023-01262-6","url":null,"abstract":"<p><p>Transcriptional corepressors Sin3, Cyc8 and Tup1 are important for downregulation of gene expression by recruiting various histone deacetylases once they gain access to defined genomic locations by interaction with pathway-specific repressor proteins. In this work we systematically investigated whether 17 yeast repressor proteins (Cti6, Dal80, Fkh1, Gal80, Mig1, Mot3, Nrg1, Opi1, Rdr1, Rox1, Sko1, Ume6, Ure2, Xbp1, Yhp1, Yox1 and Whi5) representing several unrelated regulatory pathways are able to bind to Sin3, Cyc8 and Tup1. Our results show that paired amphipathic helices 1 and 2 (PAH1 and PAH2) of Sin3 are functionally redundant for some regulatory pathways. WD40 domains of Tup1 proved to be sufficient for interaction with repressor proteins. Using length variants of selected repressors, we mapped corepressor interaction domains (CIDs) in vitro and assayed gene repression in vivo. Systematic comparison of CID minimal sequences allowed us to define several related positional patterns of hydrophobic amino acids some of which could be confirmed as functionally supported by site-directed mutagenesis. Although structural predictions indicated that certain CIDs may be α-helical, most repression domains appear to be randomly structured and must be considered as intrinsically disordered regions (IDR) adopting a defined conformation only by interaction with a corepressor.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9682479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01Epub Date: 2023-03-31DOI: 10.1007/s00294-023-01265-3
Neha Deshpande, Mary Bryk
Gene transcription is an essential and highly regulated process. In eukaryotic cells, the structural organization of nucleosomes with DNA wrapped around histone proteins impedes transcription. Chromatin remodelers, transcription factors, co-activators, and histone-modifying enzymes work together to make DNA accessible to RNA polymerase. Histone lysine methylation can positively or negatively regulate gene transcription. Methylation of histone 3 lysine 4 by SET-domain-containing proteins is evolutionarily conserved from yeast to humans. In higher eukaryotes, mutations in SET-domain proteins are associated with defects in the development and segmentation of embryos, skeletal and muscle development, and diseases, including several leukemias. Since histone methyltransferases are evolutionarily conserved, the mechanisms of gene regulation mediated by these enzymes are also conserved. Budding yeast Saccharomyces cerevisiae is an excellent model system to study the impact of histone 3 lysine 4 (H3K4) methylation on eukaryotic gene regulation. Unlike larger eukaryotes, yeast cells have only one enzyme that catalyzes H3K4 methylation, Set1. In this review, we summarize current knowledge about the impact of Set1-catalyzed H3K4 methylation on gene transcription in S. cerevisiae. We describe the COMPASS complex, factors that influence H3K4 methylation, and the roles of Set1 in gene silencing at telomeres and heterochromatin, as well as repression and activation at euchromatic loci. We also discuss proteins that "read" H3K4 methyl marks to regulate transcription and summarize alternate functions for Set1 beyond H3K4 methylation.
{"title":"Diverse and dynamic forms of gene regulation by the S. cerevisiae histone methyltransferase Set1.","authors":"Neha Deshpande, Mary Bryk","doi":"10.1007/s00294-023-01265-3","DOIUrl":"10.1007/s00294-023-01265-3","url":null,"abstract":"<p><p>Gene transcription is an essential and highly regulated process. In eukaryotic cells, the structural organization of nucleosomes with DNA wrapped around histone proteins impedes transcription. Chromatin remodelers, transcription factors, co-activators, and histone-modifying enzymes work together to make DNA accessible to RNA polymerase. Histone lysine methylation can positively or negatively regulate gene transcription. Methylation of histone 3 lysine 4 by SET-domain-containing proteins is evolutionarily conserved from yeast to humans. In higher eukaryotes, mutations in SET-domain proteins are associated with defects in the development and segmentation of embryos, skeletal and muscle development, and diseases, including several leukemias. Since histone methyltransferases are evolutionarily conserved, the mechanisms of gene regulation mediated by these enzymes are also conserved. Budding yeast Saccharomyces cerevisiae is an excellent model system to study the impact of histone 3 lysine 4 (H3K4) methylation on eukaryotic gene regulation. Unlike larger eukaryotes, yeast cells have only one enzyme that catalyzes H3K4 methylation, Set1. In this review, we summarize current knowledge about the impact of Set1-catalyzed H3K4 methylation on gene transcription in S. cerevisiae. We describe the COMPASS complex, factors that influence H3K4 methylation, and the roles of Set1 in gene silencing at telomeres and heterochromatin, as well as repression and activation at euchromatic loci. We also discuss proteins that \"read\" H3K4 methyl marks to regulate transcription and summarize alternate functions for Set1 beyond H3K4 methylation.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9442451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.1007/s00294-023-01263-5
Priya Prasad, Meena Tippana
Candida albicans is a commensal organism of the human gastrointestinal tract and a prevalent opportunistic pathogen. It exhibits different morphogenic forms to survive in different host niches with distinct environmental conditions (pH, temperature, oxidative stress, nutrients, serum, chemicals, radiation, etc.) and genetic factors (transcription factors and genes). The different morphogenic forms of C. albicans are yeast, hyphal, pseudohyphal, white, opaque, and transient gray cells, planktonic and biofilm forms of cells. These forms differ in the parameters like cellular phenotype, colony morphology, adhesion to solid surfaces, gene expression profile, and the virulent traits. Each form is functionally distinct and responds discretely to the host immune system and antifungal drugs. Hence, morphogenic plasticity is the key to virulence. In this review, we address the characteristics, the pathogenic potential of the different morphogenic forms and the conditions required for morphogenic transitions.
{"title":"Morphogenic plasticity: the pathogenic attribute of Candida albicans.","authors":"Priya Prasad, Meena Tippana","doi":"10.1007/s00294-023-01263-5","DOIUrl":"https://doi.org/10.1007/s00294-023-01263-5","url":null,"abstract":"<p><p>Candida albicans is a commensal organism of the human gastrointestinal tract and a prevalent opportunistic pathogen. It exhibits different morphogenic forms to survive in different host niches with distinct environmental conditions (pH, temperature, oxidative stress, nutrients, serum, chemicals, radiation, etc.) and genetic factors (transcription factors and genes). The different morphogenic forms of C. albicans are yeast, hyphal, pseudohyphal, white, opaque, and transient gray cells, planktonic and biofilm forms of cells. These forms differ in the parameters like cellular phenotype, colony morphology, adhesion to solid surfaces, gene expression profile, and the virulent traits. Each form is functionally distinct and responds discretely to the host immune system and antifungal drugs. Hence, morphogenic plasticity is the key to virulence. In this review, we address the characteristics, the pathogenic potential of the different morphogenic forms and the conditions required for morphogenic transitions.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9418231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.1007/s00294-023-01264-4
Felipe Pinheiro Vilela, Dália Dos Prazeres Rodrigues, Marc William Allard, Juliana Pfrimer Falcão
Salmonella enterica serovar Heidelberg (S. Heidelberg) is a zoonotic, ubiquitous, and worldwide-distributed pathogen, responsible for gastroenteritis in humans caused by the consumption of contaminated food. In this study, 11 S. Heidelberg strains isolated from chicken and bovine meat, drag swab, and animal feed between 2013 and 2017 in states of the southern region of Brazil were characterized by whole-genome sequencing (WGS) analyses. Antimicrobial resistance against 18 antimicrobials was determined by disk-diffusion and ciprofloxacin's minimum inhibitory concentration by Etest®. The search for resistance and virulence genes, plasmids, Salmonella Pathogenicity Islands (SPIs) plus multi-locus sequence typing (MLST), and single-nucleotide polymorphisms (SNPs) analyses was conducted using WGS data. All strains harbored resistance genes fosA7, aac(6')-Iaa, sul2, tet(A), blaCMY-2, mdsA, and mdsB, and point mutations in gyrA and parC. All strains showed a phenotypic multidrug-resistant profile, with resistant or intermediate resistant profiles against 14 antimicrobials tested. Plasmids ColpVC, IncC, IncX1, and IncI1-I(Alpha) were detected. Virulence genes related to adherence, macrophage induction, magnesium uptake, regulation, and type III secretion systems plus 10 SPIs were detected. All strains were assigned to ST15 and belonged to two SNP clusters showing high similarity to isolates from the United Kingdom, Chile, Germany, the Netherlands, China, South Africa, and South Korea. In conclusion, the presence of multidrug-resistant S. Heidelberg strains in Brazil showing a global genomic relationship may alert for the necessity of stronger surveillance measures by food safety and public health authorities to limit its spread to humans and animals through foods.
海德堡沙门氏菌(S. Heidelberg)是一种人畜共患的、普遍存在的、分布在世界各地的病原体,是由食用受污染食物引起的人类肠胃炎的罪魁祸首。在本研究中,通过全基因组测序(WGS)分析,从2013年至2017年巴西南部各州的鸡肉和牛肉、粪便拭子和动物饲料中分离出11株海德堡S.菌株。采用纸片扩散法测定对18种抗菌素的耐药性,并用Etest®测定环丙沙星的最低抑菌浓度。利用WGS数据寻找耐药和毒力基因、质粒、沙门氏菌致病性岛(SPIs)、多位点序列分型(MLST)和单核苷酸多态性(snp)分析。所有菌株均含有抗性基因fosA7、aac(6′)-Iaa、sul2、tet(A)、blaCMY-2、mdsA和mdsB,以及gyrA和parC的点突变。所有菌株都显示出表型多重耐药谱,对14种抗微生物药物具有耐药或中等耐药谱。检测到质粒ColpVC、IncC、IncX1、inc1 - i (Alpha)。检测到与粘附、巨噬细胞诱导、镁摄取、调节和III型分泌系统以及10个SPIs相关的毒力基因。所有菌株均归属于ST15,属于两个SNP簇,与来自英国、智利、德国、荷兰、中国、南非和韩国的分离株具有高度相似性。总之,巴西出现的耐多药海德堡S.菌株显示出全球基因组关系,这可能提醒食品安全和公共卫生当局有必要采取更强有力的监测措施,以限制其通过食品向人类和动物传播。
{"title":"Genomic analyses of drug-resistant Salmonella enterica serovar Heidelberg strains isolated from meat and related sources between 2013 and 2017 in the south region of Brazil.","authors":"Felipe Pinheiro Vilela, Dália Dos Prazeres Rodrigues, Marc William Allard, Juliana Pfrimer Falcão","doi":"10.1007/s00294-023-01264-4","DOIUrl":"https://doi.org/10.1007/s00294-023-01264-4","url":null,"abstract":"<p><p>Salmonella enterica serovar Heidelberg (S. Heidelberg) is a zoonotic, ubiquitous, and worldwide-distributed pathogen, responsible for gastroenteritis in humans caused by the consumption of contaminated food. In this study, 11 S. Heidelberg strains isolated from chicken and bovine meat, drag swab, and animal feed between 2013 and 2017 in states of the southern region of Brazil were characterized by whole-genome sequencing (WGS) analyses. Antimicrobial resistance against 18 antimicrobials was determined by disk-diffusion and ciprofloxacin's minimum inhibitory concentration by Etest®. The search for resistance and virulence genes, plasmids, Salmonella Pathogenicity Islands (SPIs) plus multi-locus sequence typing (MLST), and single-nucleotide polymorphisms (SNPs) analyses was conducted using WGS data. All strains harbored resistance genes fosA7, aac(6')-Iaa, sul2, tet(A), bla<sub>CMY-2</sub>, mdsA, and mdsB<sub>,</sub> and point mutations in gyrA and parC. All strains showed a phenotypic multidrug-resistant profile, with resistant or intermediate resistant profiles against 14 antimicrobials tested. Plasmids ColpVC, IncC, IncX1, and IncI1-I(Alpha) were detected. Virulence genes related to adherence, macrophage induction, magnesium uptake, regulation, and type III secretion systems plus 10 SPIs were detected. All strains were assigned to ST15 and belonged to two SNP clusters showing high similarity to isolates from the United Kingdom, Chile, Germany, the Netherlands, China, South Africa, and South Korea. In conclusion, the presence of multidrug-resistant S. Heidelberg strains in Brazil showing a global genomic relationship may alert for the necessity of stronger surveillance measures by food safety and public health authorities to limit its spread to humans and animals through foods.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9419640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01Epub Date: 2023-04-06DOI: 10.1007/s00294-023-01266-2
Emma Westlund, Axel Bergenstråle, Alaska Pokhrel, Helena Chan, Ulf Skoglund, Daniel O Daley, Bill Söderström
Understanding where proteins are localized in a bacterial cell is essential for understanding their function and regulation. This is particularly important for proteins that are involved in cell division, which localize at the division septum and assemble into highly regulated complexes. Current knowledge of these complexes has been greatly facilitated by super-resolution imaging using fluorescent protein fusions. Herein, we demonstrate with FtsZ that single-molecule PALM images can be obtained in-vivo using a genetically fused nanotag (ALFA), and a corresponding nanobody fused to mEos3.2. The methodology presented is applicable to other bacterial proteins.
{"title":"Application of nanotags and nanobodies for live cell single-molecule imaging of the Z-ring in Escherichia coli.","authors":"Emma Westlund, Axel Bergenstråle, Alaska Pokhrel, Helena Chan, Ulf Skoglund, Daniel O Daley, Bill Söderström","doi":"10.1007/s00294-023-01266-2","DOIUrl":"10.1007/s00294-023-01266-2","url":null,"abstract":"<p><p>Understanding where proteins are localized in a bacterial cell is essential for understanding their function and regulation. This is particularly important for proteins that are involved in cell division, which localize at the division septum and assemble into highly regulated complexes. Current knowledge of these complexes has been greatly facilitated by super-resolution imaging using fluorescent protein fusions. Herein, we demonstrate with FtsZ that single-molecule PALM images can be obtained in-vivo using a genetically fused nanotag (ALFA), and a corresponding nanobody fused to mEos3.2. The methodology presented is applicable to other bacterial proteins.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ergosterol biosynthesis pathway plays an important role in model pathogenic bacteria Saccharomyces cerevisiae, but little is known about the biosynthesis of ergosterol in the pathogenic fungus Verticillium dahliae. In this study, we identified the VdERG2 gene encoding sterol C-8 isomerase from V. dahliae and investigated its function in virulence by generating gene deletion mutants (ΔVdERG2) and complemented mutants (C-ΔVdERG2). Knockout of VdERG2 reduced ergosterol content. The conidial germination rate and conidial yield of ΔVdERG2 significantly decreased and abnormal conidia were produced. In spite of VdERG2 did not affect the utilization of carbon sources by V. dahliae, but the melanin production of ΔVdERG2 was decreased in cellulose and pectin were used as the sole carbon sources. Furthermore, the ΔVdERG2 mutants produced less microsclerotia and melanin with a significant decrease in the expression of microsclerotia and melanin-related genes VaflM, Vayg1, VDH1, VdLAC, VdSCD and VT4HR. In addition, mutants ΔVdERG2 were very sensitive to congo red (CR), sodium dodecyl sulfate (SDS) and hydrogen peroxide (H2O2) stresses, indicating that VdERG2 was involved in the cell wall and oxidative stress response. The absence of VdERG2 weakened the penetration ability of mycelium on cellophane and affected the growth of mycelium. Although ΔVdERG2 could infect cotton, its pathogenicity was significantly impaired. These phenotypic defects in ΔVdERG2 could be complemented by the reintroduction of a full-length VdERG2 gene. In summary, as a single conservative secretory protein, VdERG2 played a crucial role in ergosterol biosynthesis, nutritional differentiation and virulence in V. dahliae.
{"title":"VdERG2 was involved in ergosterol biosynthesis, nutritional differentiation and virulence of Verticillium dahliae.","authors":"Junyuan Lv, Shichao Liu, Xiaojian Zhang, Lihong Zhao, Tao Zhang, Zhigang Zhang, Zili Feng, Feng Wei, Jinglong Zhou, Ruiyuan Zhao, Hongjie Feng, Heqin Zhu, Caihong Li, Yalin Zhang","doi":"10.1007/s00294-022-01257-9","DOIUrl":"https://doi.org/10.1007/s00294-022-01257-9","url":null,"abstract":"<p><p>The ergosterol biosynthesis pathway plays an important role in model pathogenic bacteria Saccharomyces cerevisiae, but little is known about the biosynthesis of ergosterol in the pathogenic fungus Verticillium dahliae. In this study, we identified the VdERG2 gene encoding sterol C-8 isomerase from V. dahliae and investigated its function in virulence by generating gene deletion mutants (ΔVdERG2) and complemented mutants (C-ΔVdERG2). Knockout of VdERG2 reduced ergosterol content. The conidial germination rate and conidial yield of ΔVdERG2 significantly decreased and abnormal conidia were produced. In spite of VdERG2 did not affect the utilization of carbon sources by V. dahliae, but the melanin production of ΔVdERG2 was decreased in cellulose and pectin were used as the sole carbon sources. Furthermore, the ΔVdERG2 mutants produced less microsclerotia and melanin with a significant decrease in the expression of microsclerotia and melanin-related genes VaflM, Vayg1, VDH1, VdLAC, VdSCD and VT4HR. In addition, mutants ΔVdERG2 were very sensitive to congo red (CR), sodium dodecyl sulfate (SDS) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) stresses, indicating that VdERG2 was involved in the cell wall and oxidative stress response. The absence of VdERG2 weakened the penetration ability of mycelium on cellophane and affected the growth of mycelium. Although ΔVdERG2 could infect cotton, its pathogenicity was significantly impaired. These phenotypic defects in ΔVdERG2 could be complemented by the reintroduction of a full-length VdERG2 gene. In summary, as a single conservative secretory protein, VdERG2 played a crucial role in ergosterol biosynthesis, nutritional differentiation and virulence in V. dahliae.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10702501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1007/s00294-023-01261-7
Yang Meng, Chen Ding
Encapsulated Cryptococcus species are responsible for approximately 15% of AIDS-related mortality. Numerous intriguing investigations have demonstrated that mitochondria play a crucial role in the pathogen-host axis of microorganisms. Mitochondria are vital energy-generating organelles, but they also regulate a variety of cellular activities, such as fungal adaptability in the host and drug resistance. Mitochondria are also the source of reactive oxygen species, which serve as intracellular messengers but are harmful when produced in excess. Thus, precise and stringent regulation of mitochondrial activity, including oxidative phosphorylation and the ROS detoxification process, is essential to ensure that only the amount required to maintain basic biological activities and prevent ROS toxicity in the cell is maintained. However, the relationship between mitochondria and the pathogenicity of Cryptococcus remains poorly understood. In this review, we focus on transcription regulation and maintenance of mitochondrial function along the pathogen-host interaction axis, as well as prospective antifungal strategies that target mitochondria.
{"title":"Mitochondria in Cryptococcus: an update of mitochondrial transcriptional regulation in Cryptococcus.","authors":"Yang Meng, Chen Ding","doi":"10.1007/s00294-023-01261-7","DOIUrl":"https://doi.org/10.1007/s00294-023-01261-7","url":null,"abstract":"<p><p>Encapsulated Cryptococcus species are responsible for approximately 15% of AIDS-related mortality. Numerous intriguing investigations have demonstrated that mitochondria play a crucial role in the pathogen-host axis of microorganisms. Mitochondria are vital energy-generating organelles, but they also regulate a variety of cellular activities, such as fungal adaptability in the host and drug resistance. Mitochondria are also the source of reactive oxygen species, which serve as intracellular messengers but are harmful when produced in excess. Thus, precise and stringent regulation of mitochondrial activity, including oxidative phosphorylation and the ROS detoxification process, is essential to ensure that only the amount required to maintain basic biological activities and prevent ROS toxicity in the cell is maintained. However, the relationship between mitochondria and the pathogenicity of Cryptococcus remains poorly understood. In this review, we focus on transcription regulation and maintenance of mitochondrial function along the pathogen-host interaction axis, as well as prospective antifungal strategies that target mitochondria.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10720748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1007/s00294-022-01256-w
Deborah L Narh Mensah, Brenda D Wingfield, Martin P A Coetzee
Fungal secondary metabolites are often pathogenicity or virulence factors synthesized by genes contained in secondary metabolite gene clusters (SMGCs). Nonribosomal polypeptide synthetase (NRPS) clusters are SMGCs which produce peptides such as siderophores, the high affinity ferric iron chelating compounds required for iron uptake under aerobic conditions. Armillaria spp. are mostly facultative necrotrophs of woody plants. NRPS-dependent siderophore synthetase (NDSS) clusters of Armillaria spp. and selected Physalacriaceae were investigated using a comparative genomics approach. Siderophore biosynthesis by strains of selected Armillaria spp. was evaluated using CAS and split-CAS assays. At least one NRPS cluster and other clusters were detected in the genomes studied. No correlation was observed between the number and types of SMGCs and reported pathogenicity of the species studied. The genomes contained one NDSS cluster each. All NDSSs were multi-modular with the domain architecture (ATC)3(TC)2. NDSS clusters of the Armillaria spp. showed a high degree of microsynteny. In the genomes of Desarmillaria spp. and Guyanagaster necrorhizus, NDSS clusters were more syntenic with NDSS clusters of Armillaria spp. than to those of the other Physalacriaceae species studied. Three A-domain orthologous groups were identified in the NDSSs, and atypical Stachelhaus codes were predicted for the A3 orthologous group. In vitro biosynthesis of mainly hydroxamate and some catecholate siderophores was observed. Hence, Armillaria spp. generally contain one highly conserved, NDSS cluster although some interspecific variations in the products of these clusters is expected. Results from this study lays the groundwork for future studies to elucidate the molecular biology of fungal phyto-pathogenicity.
{"title":"Nonribosomal peptide synthetase gene clusters and characteristics of predicted NRPS-dependent siderophore synthetases in Armillaria and other species in the Physalacriaceae.","authors":"Deborah L Narh Mensah, Brenda D Wingfield, Martin P A Coetzee","doi":"10.1007/s00294-022-01256-w","DOIUrl":"https://doi.org/10.1007/s00294-022-01256-w","url":null,"abstract":"<p><p>Fungal secondary metabolites are often pathogenicity or virulence factors synthesized by genes contained in secondary metabolite gene clusters (SMGCs). Nonribosomal polypeptide synthetase (NRPS) clusters are SMGCs which produce peptides such as siderophores, the high affinity ferric iron chelating compounds required for iron uptake under aerobic conditions. Armillaria spp. are mostly facultative necrotrophs of woody plants. NRPS-dependent siderophore synthetase (NDSS) clusters of Armillaria spp. and selected Physalacriaceae were investigated using a comparative genomics approach. Siderophore biosynthesis by strains of selected Armillaria spp. was evaluated using CAS and split-CAS assays. At least one NRPS cluster and other clusters were detected in the genomes studied. No correlation was observed between the number and types of SMGCs and reported pathogenicity of the species studied. The genomes contained one NDSS cluster each. All NDSSs were multi-modular with the domain architecture (ATC)<sub>3</sub>(TC)<sub>2</sub>. NDSS clusters of the Armillaria spp. showed a high degree of microsynteny. In the genomes of Desarmillaria spp. and Guyanagaster necrorhizus, NDSS clusters were more syntenic with NDSS clusters of Armillaria spp. than to those of the other Physalacriaceae species studied. Three A-domain orthologous groups were identified in the NDSSs, and atypical Stachelhaus codes were predicted for the A3 orthologous group. In vitro biosynthesis of mainly hydroxamate and some catecholate siderophores was observed. Hence, Armillaria spp. generally contain one highly conserved, NDSS cluster although some interspecific variations in the products of these clusters is expected. Results from this study lays the groundwork for future studies to elucidate the molecular biology of fungal phyto-pathogenicity.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10713453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1007/s00294-022-01258-8
Dimitra Dialynaki, Athanasia Stavropoulou, Maria Laskou, Despina Alexandraki
Although copper is an essential trace element for cell function and viability, its excess can lead to protein oxidation, DNA cleavage, and ultimate cell damage. Cells have established a variety of regulatory mechanisms to ensure copper ion homeostasis. In Saccharomyces cerevisiae, copper sensing and response to copper deficiency are regulated by the transcription factor Mac1. Our group has previously reported that in addition to copper, several chromatin proteins modulate Mac1 functionality. In this study, based on a synthetic growth deficiency phenotype, we showed that the Cu/Zn superoxide dismutase Sod1 plays an important role in Mac1 transcriptional activity, in unchallenged nutrient-rich growth conditions. Sod1 is a multipotent cytoplasmic and mitochondrial enzyme, whose main known function is to detoxify the cell from superoxide ions. It has been previously reported that Sod1 also enters the nucleus and affects the transcription of several genes, some of which are involved in copper homeostasis under Cu-depleted (Wood and Thiele in J Biol Chem 284:404-413, 2009) or only under specific oxidative stress conditions (Dong et al. Mol Cell Biol 33:4041-4050, 2013; Tsang et al. Nar Commun 8:3446, 2014). We have shown that Sod1 physically interacts with Mac1 transcription factor and is important for the transactivation as well as its DNA-binding activities. On the other hand, a constitutively active mutant of Mac1 is not affected functionally by the Sod1 ablation, pointing out that Sod1 contributes to the maintenance of the copper-unchelated state of Mac1. In conclusion, we showed that Sod1-Mac1 interaction is vital for Mac1 functionality, regardless of copper medium deficiency, in unchallenged growth conditions, and we suggest that Sod1 enzymatic activity may modify the redox state of the cysteine-rich motifs in the Mac1 DNA-binding and transactivation domains.
虽然铜是维持细胞功能和活力所必需的微量元素,但过量的铜会导致蛋白质氧化、DNA分裂和最终的细胞损伤。细胞已经建立了多种调节机制来确保铜离子的稳态。在酿酒酵母(Saccharomyces cerevisiae)中,铜的感知和对缺铜的反应受转录因子Mac1的调控。我们的团队之前报道过,除了铜外,还有几种染色质蛋白调节Mac1的功能。在这项研究中,基于合成生长缺陷表型,我们发现在无挑战的富营养生长条件下,Cu/Zn超氧化物歧化酶Sod1在Mac1转录活性中起重要作用。Sod1是一种多能的细胞质和线粒体酶,其主要功能是将细胞从超氧离子中解毒。此前有报道称,Sod1也进入细胞核并影响几个基因的转录,其中一些基因在cu -贫状态下参与铜稳态(Wood and Thiele in J Biol Chem 284:404-413, 2009)或仅在特定氧化应激条件下参与铜稳态(Dong et al.)。生物工程学报(英文版);2013;Tsang等人。Nar comm 8:34 . 46, 2014)。我们已经证明Sod1与Mac1转录因子物理相互作用,并且对其反式激活及其dna结合活性很重要。另一方面,Mac1的本构活性突变体在功能上不受Sod1消融的影响,这表明Sod1有助于维持Mac1的铜不螯合状态。总之,我们发现在无挑战的生长条件下,无论铜培养基缺乏,Sod1-Mac1相互作用对Mac1的功能至关重要,我们认为Sod1酶活性可能会改变Mac1 dna结合和反激活域中富含半胱氨酸的基序的氧化还原状态。
{"title":"The essential liaison of two copper proteins: the Cu-sensing transcription factor Mac1 and the Cu/Zn superoxide dismutase Sod1 in Saccharomyces cerevisiae.","authors":"Dimitra Dialynaki, Athanasia Stavropoulou, Maria Laskou, Despina Alexandraki","doi":"10.1007/s00294-022-01258-8","DOIUrl":"https://doi.org/10.1007/s00294-022-01258-8","url":null,"abstract":"<p><p>Although copper is an essential trace element for cell function and viability, its excess can lead to protein oxidation, DNA cleavage, and ultimate cell damage. Cells have established a variety of regulatory mechanisms to ensure copper ion homeostasis. In Saccharomyces cerevisiae, copper sensing and response to copper deficiency are regulated by the transcription factor Mac1. Our group has previously reported that in addition to copper, several chromatin proteins modulate Mac1 functionality. In this study, based on a synthetic growth deficiency phenotype, we showed that the Cu/Zn superoxide dismutase Sod1 plays an important role in Mac1 transcriptional activity, in unchallenged nutrient-rich growth conditions. Sod1 is a multipotent cytoplasmic and mitochondrial enzyme, whose main known function is to detoxify the cell from superoxide ions. It has been previously reported that Sod1 also enters the nucleus and affects the transcription of several genes, some of which are involved in copper homeostasis under Cu-depleted (Wood and Thiele in J Biol Chem 284:404-413, 2009) or only under specific oxidative stress conditions (Dong et al. Mol Cell Biol 33:4041-4050, 2013; Tsang et al. Nar Commun 8:3446, 2014). We have shown that Sod1 physically interacts with Mac1 transcription factor and is important for the transactivation as well as its DNA-binding activities. On the other hand, a constitutively active mutant of Mac1 is not affected functionally by the Sod1 ablation, pointing out that Sod1 contributes to the maintenance of the copper-unchelated state of Mac1. In conclusion, we showed that Sod1-Mac1 interaction is vital for Mac1 functionality, regardless of copper medium deficiency, in unchallenged growth conditions, and we suggest that Sod1 enzymatic activity may modify the redox state of the cysteine-rich motifs in the Mac1 DNA-binding and transactivation domains.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10777103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01Epub Date: 2022-11-30DOI: 10.1007/s00294-022-01259-7
Mathijs Nieuwenhuis, Jeroen Groeneveld, Duur K Aanen
Fungal and plant mitochondria are known to exchange DNA with retroviral plasmids. Transfer of plasmid DNA to the organellar genome is best known and occurs through wholesale insertion of the plasmid. Less well known is the transfer of organellar DNA to plasmids, in particular tRNA genes. Presently, it is unknown whether fungal plasmids can adopt mitochondrial functions such as tRNA production through horizontal gene transfer. In this paper, we studied the exchange of DNA between fungal linear plasmids and fungal mtDNA, mainly focusing on the basidiomycete family Lyophyllaceae. We report at least six independent transfers of complete tRNA genes to fungal plasmids. Furthermore, we discovered two independent cases of loss of a tRNA gene from a fungal mitochondrial genome following transfer of such a gene to a linear mitochondrial plasmid. We propose that loss of a tRNA gene from mtDNA following its transfer to a plasmid creates a mutualistic dependency of the host mtDNA on the plasmid. We also find that tRNA genes transferred to plasmids encode codons that occur at the lowest frequency in the host mitochondrial genomes, possibly due to a higher number of unused transcripts. We discuss the potential consequences of mtDNA transfer to plasmids for both the host mtDNA and the plasmid.
已知真菌和植物线粒体可与逆转录病毒质粒交换 DNA。质粒 DNA 向细胞器基因组的转移最广为人知,是通过质粒的整体插入进行的。而细胞器 DNA 向质粒的转移,尤其是 tRNA 基因的转移,则鲜为人知。目前,人们还不知道真菌质粒能否通过水平基因转移获得线粒体的功能,如生产 tRNA。在本文中,我们研究了真菌线性质粒与真菌 mtDNA 之间的 DNA 交换,主要集中在基生真菌 Lyophyllaceae 家族。我们报告了至少六种独立的完整 tRNA 基因转移到真菌质粒的情况。此外,我们还发现了两例将 tRNA 基因转移到线粒体质粒后真菌线粒体基因组中 tRNA 基因丢失的独立案例。我们认为,将线粒体 DNA 中的 tRNA 基因转移到质粒上后,宿主的线粒体 DNA 会对质粒产生一种相互依赖的关系。我们还发现,转入质粒的 tRNA 基因编码的密码子在宿主线粒体基因组中出现的频率最低,这可能是由于未使用的转录本数量较多。我们讨论了将 mtDNA 转移到质粒对宿主 mtDNA 和质粒的潜在影响。
{"title":"Horizontal transfer of tRNA genes to mitochondrial plasmids facilitates gene loss from fungal mitochondrial DNA.","authors":"Mathijs Nieuwenhuis, Jeroen Groeneveld, Duur K Aanen","doi":"10.1007/s00294-022-01259-7","DOIUrl":"10.1007/s00294-022-01259-7","url":null,"abstract":"<p><p>Fungal and plant mitochondria are known to exchange DNA with retroviral plasmids. Transfer of plasmid DNA to the organellar genome is best known and occurs through wholesale insertion of the plasmid. Less well known is the transfer of organellar DNA to plasmids, in particular tRNA genes. Presently, it is unknown whether fungal plasmids can adopt mitochondrial functions such as tRNA production through horizontal gene transfer. In this paper, we studied the exchange of DNA between fungal linear plasmids and fungal mtDNA, mainly focusing on the basidiomycete family Lyophyllaceae. We report at least six independent transfers of complete tRNA genes to fungal plasmids. Furthermore, we discovered two independent cases of loss of a tRNA gene from a fungal mitochondrial genome following transfer of such a gene to a linear mitochondrial plasmid. We propose that loss of a tRNA gene from mtDNA following its transfer to a plasmid creates a mutualistic dependency of the host mtDNA on the plasmid. We also find that tRNA genes transferred to plasmids encode codons that occur at the lowest frequency in the host mitochondrial genomes, possibly due to a higher number of unused transcripts. We discuss the potential consequences of mtDNA transfer to plasmids for both the host mtDNA and the plasmid.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10736425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}