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[PMID]:29311576
[Au] Autor:Razew M; Warkocki Z; Taube M; Kolondra A; Czarnocki-Cieciura M; Nowak E; Labedzka-Dmoch K; Kawinska A; Piatkowski J; Golik P; Kozak M; Dziembowski A; Nowotny M
[Ad] Endereço:Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, Trojdena 4, 02-109, Warsaw, Poland.
[Ti] Título:Structural analysis of mtEXO mitochondrial RNA degradosome reveals tight coupling of nuclease and helicase components.
[So] Source:Nat Commun;9(1):97, 2018 01 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nuclease and helicase activities play pivotal roles in various aspects of RNA processing and degradation. These two activities are often present in multi-subunit complexes from nucleic acid metabolism. In the mitochondrial exoribonuclease complex (mtEXO) both enzymatic activities are tightly coupled making it an excellent minimal system to study helicase-exoribonuclease coordination. mtEXO is composed of Dss1 3'-to-5' exoribonuclease and Suv3 helicase. It is the master regulator of mitochondrial gene expression in yeast. Here, we present the structure of mtEXO and a description of its mechanism of action. The crystal structure of Dss1 reveals domains that are responsible for interactions with Suv3. Importantly, these interactions are compatible with the conformational changes of Suv3 domains during the helicase cycle. We demonstrate that mtEXO is an intimate complex which forms an RNA-binding channel spanning its entire structure, with Suv3 helicase feeding the 3' end of the RNA toward the active site of Dss1.
[Mh] Termos MeSH primário: Endorribonucleases/metabolismo
Exorribonucleases/metabolismo
Proteínas Mitocondriais/metabolismo
Complexos Multienzimáticos/metabolismo
Polirribonucleotídeo Nucleotidiltransferase/metabolismo
RNA Helicases/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Sequência de Bases
Candida glabrata/enzimologia
Candida glabrata/genética
Candida glabrata/metabolismo
Cristalografia por Raios X
RNA Helicases DEAD-box/química
RNA Helicases DEAD-box/genética
RNA Helicases DEAD-box/metabolismo
Endorribonucleases/química
Endorribonucleases/genética
Exorribonucleases/química
Exorribonucleases/genética
Proteínas Mitocondriais/química
Proteínas Mitocondriais/genética
Complexos Multienzimáticos/química
Complexos Multienzimáticos/genética
Conformação de Ácido Nucleico
Polirribonucleotídeo Nucleotidiltransferase/química
Polirribonucleotídeo Nucleotidiltransferase/genética
Ligação Proteica
Conformação Proteica
RNA/química
RNA/genética
RNA/metabolismo
RNA Helicases/química
RNA Helicases/genética
Saccharomyces cerevisiae/enzimologia
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/química
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Mitochondrial Proteins); 0 (Multienzyme Complexes); 0 (RNA, mitochondrial); 0 (Saccharomyces cerevisiae Proteins); 0 (degradosome); 63231-63-0 (RNA); EC 2.7.7.8 (Polyribonucleotide Nucleotidyltransferase); EC 3.1.- (Endoribonucleases); EC 3.1.- (Exoribonucleases); EC 3.1.13.1 (DSS1 protein, S cerevisiae); EC 3.6.1.- (SUV3 protein, S cerevisiae); EC 3.6.4.13 (DEAD-box RNA Helicases); EC 3.6.4.13 (RNA Helicases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02570-5


  2 / 1228 MEDLINE  
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[PMID]:29235765
[Au] Autor:Trush MM; Kovalishyn VV; Blagodatnyi VM; Brovarets VS; Pilyo SG; Prokopenko VM; Hodyna DM; Metelytsia LO
[Ti] Título:QSAR studies and antimicrobial potential of 1,3-thiazolylphosphonium salts.
[So] Source:Ukr Biochem J;88(4):57-65, 2016 Jul-Aug.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:The regression QSAR models were built to predict the antimicrobial activity of new thiazole derivatives. Compounds with high predicting activity were synthesized and evaluated against Gram-positive and Gram-negative bacteria and fungi. 1,3-Thiazole-4-ylphosphonium salts 4 and 5 displayed good antibacterial properties and high antifungal activity. The predictions are in a good agreement with the experiment results, which indicate the good predictive power of the created QSAR models.
[Mh] Termos MeSH primário: Antibacterianos/síntese química
Antifúngicos/síntese química
Compostos Organofosforados/síntese química
Tiazóis/síntese química
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Antifúngicos/farmacologia
Bacillus subtilis/efeitos dos fármacos
Bacillus subtilis/crescimento & desenvolvimento
Candida/efeitos dos fármacos
Candida/crescimento & desenvolvimento
Candida albicans/efeitos dos fármacos
Candida albicans/crescimento & desenvolvimento
Candida glabrata/efeitos dos fármacos
Candida glabrata/crescimento & desenvolvimento
Escherichia coli/efeitos dos fármacos
Escherichia coli/crescimento & desenvolvimento
Testes de Sensibilidade Microbiana
Compostos Organofosforados/farmacologia
Pseudomonas aeruginosa/efeitos dos fármacos
Pseudomonas aeruginosa/crescimento & desenvolvimento
Relação Quantitativa Estrutura-Atividade
Tiazóis/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antifungal Agents); 0 (Organophosphorus Compounds); 0 (Thiazoles)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.04.057


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[PMID]:28911043
[Au] Autor:Arendrup MC; Patterson TF
[Ad] Endereço:Unit of Mycology, Statens Serum Institut.
[Ti] Título:Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment.
[So] Source:J Infect Dis;216(suppl_3):S445-S451, 2017 Aug 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Invasive Candida infections remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. A limited number of antifungal agents from only a few drug classes are available to treat patients with these serious infections. Resistance can be either intrinsic or acquired. Resistance mechanisms are not exchanged between Candida; thus, acquired resistance either emerges in response to an antifungal selection pressure in the individual patient or, more rarely, occur due to horizontal transmission of resistant strains between patients. Although multidrug resistance is uncommon, increasing reports of multidrug resistance to the azoles, echinocandins, and polyenes have occurred in several Candida species, most notably Candida glabrata and more recently Candida auris. Drivers are overall antifungal use, subtherapeutic drug levels at sites of infection/colonization, drug sequestration in the biofilm matrix, and, in the setting of outbreaks, suboptimal infection control. Moreover, recent research suggests that DNA mismatch repair gene mutations may facilitate acquisition of resistance mutations in C. glabrata specifically. Diagnosis of antifungal-resistant Candida infections is critical to the successful management of patients with these infections. Reduction of unnecessary use of antifungals via antifungal stewardship is critical to limit multidrug resistance emergence.
[Mh] Termos MeSH primário: Candida glabrata/efeitos dos fármacos
Candida/efeitos dos fármacos
Candidíase Invasiva/tratamento farmacológico
Farmacorresistência Fúngica Múltipla
[Mh] Termos MeSH secundário: Animais
Antifúngicos/farmacologia
Azóis/farmacologia
Candida/classificação
Candidíase Invasiva/epidemiologia
Estado Terminal/epidemiologia
Estado Terminal/terapia
Modelos Animais de Doenças
Equinocandinas/farmacologia
Seres Humanos
Testes de Sensibilidade Microbiana
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Azoles); 0 (Echinocandins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix131


  4 / 1228 MEDLINE  
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[PMID]:28842359
[Au] Autor:Song RY; Wang XB; Yin GP; Liu RH; Kong LY; Yang MH
[Ad] Endereço:State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
[Ti] Título:Isocoumarin derivatives from the endophytic fungus, Pestalotiopsis sp.
[So] Source:Fitoterapia;122:115-118, 2017 Oct.
[Is] ISSN:1873-6971
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Five new isocoumarin derivatives, pestalactone A-C (1-3) and pestapyrone D-E (4-5), together with two known compounds (6-7) were isolated from the solid cultures of the endophytic fungus Pestalotiopsis sp. obtained from Photinia frasery. Their structures were mainly determined by extensive spectroscopic analysis, Mo (OCOCH ) -induced electronic circular dichroism (ECD), and ECD calculation. Compounds 1 and 2 were rare isocoumarin derivatives and derived from distinctive polyketide pathways. Compound 3 exhibited potent antifungal activity against Candida glabrata (ATCC 90030) with an MIC value of 3.49±0.21µg/mL.
[Mh] Termos MeSH primário: Antifúngicos/química
Xylariales/química
[Mh] Termos MeSH secundário: Antifúngicos/isolamento & purificação
Candida glabrata/efeitos dos fármacos
Endófitos/química
Isocumarinas/química
Isocumarinas/isolamento & purificação
Testes de Sensibilidade Microbiana
Estrutura Molecular
Photinia/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Isocoumarins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170827
[St] Status:MEDLINE


  5 / 1228 MEDLINE  
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[PMID]:28768479
[Au] Autor:Li D; Xia R; Zhang Q; Bai C; Li Z; Zhang P
[Ad] Endereço:Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Huanhu West Road, Ti-Yuan-Bei, Hexi District, Tianjin, 300060, People's Republic of China. lidingly@126.
[Ti] Título:Evaluation of candidemia in epidemiology and risk factors among cancer patients in a cancer center of China: an 8-year case-control study.
[So] Source:BMC Infect Dis;17(1):536, 2017 Aug 03.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Candidemia is the worldwide life-threaten disease, especially in cancer patients. This study was aimed to identify and evaluate the risk factors of candidemia in cancer patients, which will prompt the improvement on current therapeutic strategies and prognosis. METHODS: A retrospective, case-control study was conducted from inpatients of Tianjin Medical University Cancer Institute and Hospital, during 2006 to 2013. Analyses were performed between cancer patients with candidemia as study case, and patients with bacterial bloodstream infections as control. Each case was matched up with two controls, for gender and inpatient duration. Candida species, clinical characteristics, risk factors and outcomes were reviewed in details. RESULTS: Total number of 80 cases and 160 controls were enrolled and analyzed in this study. Candida albicans was identified as the most prevalent species and account for 55.0% candidemia, followed by Candida parapsilosis complex (21.3%), Candida tropicalis (8.8%), Candida glabrata complex (7.5%), Candida lusitaniae (3.8%), and Candida famata (3.8%). The crude mortality at 30-days of candidemia was up to 30.0%, which is significantly higher than bacterial bloodstream infections (p = 0.006). Logistical analysis demonstrated that total parenteral nutrition >5 days (p = 0.036), urinary catheter >2 days (p = 0.001), distant organ metastasis of cancer (p = 0.002) and gastrointestinal cancer (p = 0.042) were the independent risk factors for candidemia. CONCLUSIONS: Candidemia showed significant higher mortality than bacterial bloodstream infections, C. albicans was cited as the primary pathogen. Total parenteral nutrition, urinary catheter, distant organ metastasis of cancer and gastrointestinal cancer are independent predictors for candidemia, this findings provides potential therapeutic targets for improving the outcome.
[Mh] Termos MeSH primário: Candidemia/epidemiologia
Candidemia/microbiologia
Neoplasias/complicações
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Candida/patogenicidade
Candida albicans/patogenicidade
Candida glabrata/patogenicidade
Candidemia/tratamento farmacológico
Estudos de Casos e Controles
Infecções Relacionadas a Cateter/epidemiologia
Infecções Relacionadas a Cateter/microbiologia
China/epidemiologia
Feminino
Seres Humanos
Masculino
Testes de Sensibilidade Microbiana
Meia-Idade
Prevalência
Prognóstico
Estudos Retrospectivos
Fatores de Risco
Cateteres Urinários
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2636-x


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[PMID]:28757210
[Au] Autor:Bonnet A; Grosso AR; Elkaoutari A; Coleno E; Presle A; Sridhara SC; Janbon G; Géli V; de Almeida SF; Palancade B
[Ad] Endereço:Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France.
[Ti] Título:Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic Instability.
[So] Source:Mol Cell;67(4):608-621.e6, 2017 Aug 17.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transcription is a source of genetic instability that can notably result from the formation of genotoxic DNA:RNA hybrids, or R-loops, between the nascent mRNA and its template. Here we report an unexpected function for introns in counteracting R-loop accumulation in eukaryotic genomes. Deletion of endogenous introns increases R-loop formation, while insertion of an intron into an intronless gene suppresses R-loop accumulation and its deleterious impact on transcription and recombination in yeast. Recruitment of the spliceosome onto the mRNA, but not splicing per se, is shown to be critical to attenuate R-loop formation and transcription-associated genetic instability. Genome-wide analyses in a number of distant species differing in their intron content, including human, further revealed that intron-containing genes and the intron-richest genomes are best protected against R-loop accumulation and subsequent genetic instability. Our results thereby provide a possible rationale for the conservation of introns throughout the eukaryotic lineage.
[Mh] Termos MeSH primário: DNA Fúngico/genética
Instabilidade Genômica
Íntrons
Ácidos Nucleicos Heteroduplexes/genética
RNA Fúngico/genética
Transcrição Genética
[Mh] Termos MeSH secundário: Candida glabrata/genética
Candida glabrata/metabolismo
Linhagem Celular
Biologia Computacional
Cryptococcus neoformans/genética
Cryptococcus neoformans/metabolismo
Dano ao DNA
DNA Fúngico/química
DNA Fúngico/metabolismo
Bases de Dados Genéticas
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
Regulação Fúngica da Expressão Gênica
Genótipo
Seres Humanos
Conformação de Ácido Nucleico
Ácidos Nucleicos Heteroduplexes/química
Ácidos Nucleicos Heteroduplexes/metabolismo
Fenótipo
Processamento de RNA
RNA Fúngico/química
RNA Fúngico/metabolismo
Ribonucleoproteínas/genética
Ribonucleoproteínas/metabolismo
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Schizosaccharomyces/genética
Schizosaccharomyces/metabolismo
Spliceossomos/genética
Spliceossomos/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Fungal); 0 (Fungal Proteins); 0 (Nucleic Acid Heteroduplexes); 0 (RNA, Fungal); 0 (Ribonucleoproteins); 0 (messenger ribonucleoprotein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE


  7 / 1228 MEDLINE  
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[PMID]:28700656
[Au] Autor:Nagayoshi Y; Miyazaki T; Shimamura S; Nakayama H; Minematsu A; Yamauchi S; Takazono T; Nakamura S; Yanagihara K; Kohno S; Mukae H; Izumikawa K
[Ad] Endereço:Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
[Ti] Título:Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species.
[So] Source:PLoS One;12(7):e0180990, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole susceptibility in C. glabrata. In the present study, we have evaluated the effects of clorgyline on susceptibility of C. glabrata to not only azoles, but also to micafungin and amphotericin B, using wild-type and several mutant strains. The addition of clorgyline to the culture media increased fluconazole susceptibility of a C. glabrata wild-type strain, whereas micafungin and amphotericin B susceptibilities were markedly decreased. These phenomena were also observed in other medically important Candida species, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida krusei. Expression levels of CDR1, CDR2 and PDR1 mRNAs and an amount of Cdr1 protein in the C. glabrata wild-type strain were highly increased in response to the treatment with clorgyline. However, loss of Cdr1, Cdr2, Pdr1, and a putative clorgyline target (Fms1), which is an ortholog of human MAO-A, or overexpression of CDR1 did not affect the decreased susceptibility to micafungin and amphotericin B in the presence of clorgyline. The presence of other azole efflux pump inhibitors including milbemycin A4 oxime and carbonyl cyanide 3-chlorophenylhydrazone also decreased micafungin susceptibility in C. glabrata wild-type, Δcdr1, Δcdr2, and Δpdr1 strains. These findings suggest that azole efflux pump inhibitors increase azole susceptibility but concurrently induce decreased susceptibility to other classes of antifungals independent of azole transporter functions.
[Mh] Termos MeSH primário: Antifúngicos/farmacologia
Candida glabrata/metabolismo
Candida/metabolismo
[Mh] Termos MeSH secundário: Anfotericina B/farmacologia
Transporte Biológico
Candida/efeitos dos fármacos
Candida glabrata/efeitos dos fármacos
Farmacorresistência Fúngica
Equinocandinas/farmacologia
Fluconazol/farmacologia
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
Lipopeptídeos/farmacologia
Testes de Sensibilidade Microbiana
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Echinocandins); 0 (Fungal Proteins); 0 (Lipopeptides); 7XU7A7DROE (Amphotericin B); 8VZV102JFY (Fluconazole); R10H71BSWG (micafungin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180990


  8 / 1228 MEDLINE  
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[PMID]:28566663
[Au] Autor:Hirai K; Inukai T; Nakayama H
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science.
[Ti] Título:Promising Therapies for Fungal Infection Based on the Study to Elucidate Mechanisms to Cope with Stress in Candida Species [Translated Article].
[So] Source:Med Mycol J;58(2):E79-E86, 2017.
[Is] ISSN:1882-0476
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:In recent years, the incidence of fungal infections has been increasing, particularly among patients with immune systems compromised by human immunodeficiency virus infection, organ transplantation, and/or chemotherapy for cancer. Current therapies for treating systemic fungal infection have limited effectiveness and have created problems of adverse reactions and drug resistance. These issues therefore motivate us to develop novel antifungals. Elucidation of stress response mechanisms and virulence factors in pathogenic fungi is required in developing an effective antifungal strategy. There are actually numerous studies concerning various stress responses in several important fungal pathogens. Among these responses, we focused on stress response for iron starvation to identify potential targets for novel antifungals because iron starvation occurs in blood, where pathogenic fungi often infect. Here we show recent progress of studies on iron homeostasis in Candida species, especially focusing on Candida glabrata, and propose novel antifungal targets.
[Mh] Termos MeSH primário: Antifúngicos/uso terapêutico
Candida glabrata/metabolismo
Candida glabrata/patogenicidade
Candidíase/tratamento farmacológico
Candidíase/microbiologia
Descoberta de Drogas
Infecções Fúngicas Invasivas/tratamento farmacológico
Infecções Fúngicas Invasivas/microbiologia
Micoses/tratamento farmacológico
[Mh] Termos MeSH secundário: Antifúngicos/efeitos adversos
Homeostase
Seres Humanos
Hospedeiro Imunocomprometido
Ferro/metabolismo
Fatores de Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Virulence Factors); E1UOL152H7 (Iron)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.3314/mmj.17.007


  9 / 1228 MEDLINE  
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[PMID]:28489916
[Au] Autor:Bouklas T; Alonso-Crisóstomo L; Székely T; Diago-Navarro E; Orner EP; Smith K; Munshi MA; Del Poeta M; Balázsi G; Fries BC
[Ad] Endereço:Department of Medicine, Division of Infectious Diseases, Stony Brook University, Stony Brook, New York, United States of America.
[Ti] Título:Generational distribution of a Candida glabrata population: Resilient old cells prevail, while younger cells dominate in the vulnerable host.
[So] Source:PLoS Pathog;13(5):e1006355, 2017 May.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Similar to other yeasts, the human pathogen Candida glabrata ages when it undergoes asymmetric, finite cell divisions, which determines its replicative lifespan. We sought to investigate if and how aging changes resilience of C. glabrata populations in the host environment. Our data demonstrate that old C. glabrata are more resistant to hydrogen peroxide and neutrophil killing, whereas young cells adhere better to epithelial cell layers. Consequently, virulence of old compared to younger C. glabrata cells is enhanced in the Galleria mellonella infection model. Electron microscopy images of old C. glabrata cells indicate a marked increase in cell wall thickness. Comparison of transcriptomes of old and young C. glabrata cells reveals differential regulation of ergosterol and Hog pathway associated genes as well as adhesion proteins, and suggests that aging is accompanied by remodeling of the fungal cell wall. Biochemical analysis supports this conclusion as older cells exhibit a qualitatively different lipid composition, leading to the observed increased emergence of fluconazole resistance when grown in the presence of fluconazole selection pressure. Older C. glabrata cells accumulate during murine and human infection, which is statistically unlikely without very strong selection. Therefore, we tested the hypothesis that neutrophils constitute the predominant selection pressure in vivo. When we altered experimentally the selection pressure by antibody-mediated removal of neutrophils, we observed a significantly younger pathogen population in mice. Mathematical modeling confirmed that differential selection of older cells is sufficient to cause the observed demographic shift in the fungal population. Hence our data support the concept that pathogenesis is affected by the generational age distribution of the infecting C. glabrata population in a host. We conclude that replicative aging constitutes an emerging trait, which is selected by the host and may even play an unanticipated role in the transition from a commensal to a pathogen state.
[Mh] Termos MeSH primário: Candida glabrata/fisiologia
Candida glabrata/patogenicidade
Candidíase/microbiologia
Farmacorresistência Fúngica
[Mh] Termos MeSH secundário: Animais
Antifúngicos/farmacologia
Candida glabrata/efeitos dos fármacos
Candida glabrata/genética
Adesão Celular
Divisão Celular
Parede Celular/ultraestrutura
Fluconazol/farmacologia
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
Seres Humanos
Peróxido de Hidrogênio/farmacologia
Camundongos
Mariposas
Neutrófilos/microbiologia
Fenótipo
Seleção Genética
Análise de Sequência de RNA
Fatores de Tempo
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Fungal Proteins); 8VZV102JFY (Fluconazole); BBX060AN9V (Hydrogen Peroxide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006355


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[PMID]:28364558
[Au] Autor:Chapman B; Slavin M; Marriott D; Halliday C; Kidd S; Arthur I; Bak N; Heath CH; Kennedy K; Morrissey CO; Sorrell TC; van Hal S; Keighley C; Goeman E; Underwood N; Hajkowicz K; Hofmeyr A; Leung M; Macesic N; Botes J; Blyth C; Cooley L; George CR; Kalukottege P; Kesson A; McMullan B; Baird R; Robson J; Korman TM; Pendle S; Weeks K; Liu E; Cheong E; Chen S; Australian and New Zealand Mycoses Interest Group
[Ad] Endereço:Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
[Ti] Título:Changing epidemiology of candidaemia in Australia.
[So] Source:J Antimicrob Chemother;72(4):1103-1108, 2017 Apr 01.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia. Methods: These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne™. Results: A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 population. The median patient age was 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles; only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/echinocandin co-resistance. Conclusions: We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.
[Mh] Termos MeSH primário: Antifúngicos/farmacologia
Candida/efeitos dos fármacos
Candida/isolamento & purificação
Candidemia/epidemiologia
Candidemia/microbiologia
[Mh] Termos MeSH secundário: Austrália/epidemiologia
Azóis/farmacologia
Candida/classificação
Candida/genética
Candida glabrata/efeitos dos fármacos
Candida glabrata/genética
Candida glabrata/isolamento & purificação
Candida tropicalis/efeitos dos fármacos
Candida tropicalis/genética
Candida tropicalis/isolamento & purificação
Farmacorresistência Fúngica/genética
Equinocandinas/farmacologia
Feminino
Fluconazol/farmacologia
Seres Humanos
Incidência
Lipopeptídeos/farmacologia
Masculino
Testes de Sensibilidade Microbiana/métodos
Análise de Sequência de DNA/métodos
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
Triazóis/farmacologia
Voriconazol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Azoles); 0 (Echinocandins); 0 (Lipopeptides); 0 (Triazoles); 6TK1G07BHZ (posaconazole); 8VZV102JFY (Fluconazole); 9HLM53094I (anidulafungin); F0XDI6ZL63 (caspofungin); JFU09I87TR (Voriconazole); R10H71BSWG (micafungin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170402
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkw422



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