Microbial Cell最新文献_第10页

Histone H3E73Q and H4E53A mutations cause recombinogenic DNA damage. 组蛋白H3E73Q和H4E53A突变引起重组性DNA损伤。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2020-04-24 DOI: 10.15698/mic2020.07.723

Pedro Ortega, Desiré García-Pichardo, Marta San Martin-Alonso, Ana G Rondón, Belén Gómez-González, Andrés Aguilera

引用次数: 0

A novel c-di-GMP signal system regulates biofilm formation in Pseudomonas aeruginosa. 一种新的c-di-GMP信号系统调控铜绿假单胞菌的生物膜形成。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2020-04-23 DOI: 10.15698/mic2020.06.720

Gukui Chen, Haihua Liang

{"title":"A novel c-di-GMP signal system regulates biofilm formation in Pseudomonas aeruginosa.","authors":"Gukui Chen, Haihua Liang","doi":"10.15698/mic2020.06.720","DOIUrl":"https://doi.org/10.15698/mic2020.06.720","url":null,"abstract":"The bacterial second messenger cyclic-di-GMP (c-di-GMP) controls biofilm formation and other phenotypes relevant to pathogenesis. The human pathogen Pseudomonas aeruginosa encodes 17 diguanylate cyclase (DGCs) proteins which are required for c-di-GMP synthesis. Therefore, the c-di-GMP regulatory system in P. aeruginosa is highly sophisticated. SiaD, one of the DGC enzymes, is co-transcribed with SiaA/B/C and has been shown to be essential for bacterial aggregate formation in response to environmental stress. However, the detailed function of this operon remains unknown. In our recent paper (Chen et al., doi: 10.15252/embj.2019103412), we have demonstrated that the siaABCD operon encodes a signaling network that regulates biofilm and aggregate formation by modulating the enzymatic activity of SiaD. Among this signaling system, SiaC interaction with SiaD promotes the diguanylate cyclase activity of SiaD and subsequently facilities the intracellular c-di-GMP synthesis; SiaB is a unique protein kinase that phosphorylates SiaC, whereas SiaA phosphatase can dephosphorylate SiaC. The phosphorylation state of SiaC is critical for its interaction with SiaD, which will switch on or off the DGC activity of SiaD. This report unveils a novel signaling system that controls biofilm formation, which may provide a potential target for developing antimicrobial drugs.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 6","pages":"160-161"},"PeriodicalIF":4.6,"publicationDate":"2020-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38052534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Sulforaphane alters the acidification of the yeast vacuole. 萝卜硫素改变酵母液泡的酸化。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2020-03-20 DOI: 10.15698/mic2020.05.716

Alexander Wilcox, Michael Murphy, Douglass Tucker, David Laprade, Breton Roussel, Christopher Chin, Victoria Hallisey, Noah Kozub, Abraham Brass, Nicanor Austriaco

{"title":"Sulforaphane alters the acidification of the yeast vacuole.","authors":"Alexander Wilcox, Michael Murphy, Douglass Tucker, David Laprade, Breton Roussel, Christopher Chin, Victoria Hallisey, Noah Kozub, Abraham Brass, Nicanor Austriaco","doi":"10.15698/mic2020.05.716","DOIUrl":"https://doi.org/10.15698/mic2020.05.716","url":null,"abstract":"Sulforaphane (SFN) is a compound [1-isothiocyanato-4-(methylsulfinyl)-butane] found in broccoli and other cruciferous vegetables that is currently of interest because of its potential as a chemopreventive and a chemotherapeutic drug. Recent studies in a diverse range of cellular and animal models have shown that SFN is involved in multiple intracellular pathways that regulate xenobiotic metabolism, inflammation, cell death, cell cycle progression, and epigenetic regulation. In order to better understand the mechanisms of action behind SFN-induced cell death, we undertook an unbiased genome wide screen with the yeast knockout (YKO) library to identify SFN sensitive (SFNS) mutants. The mutants were enriched with knockouts in genes linked to vacuolar function suggesting a link between this organelle and SFN's mechanism of action in yeast. Our subsequent work revealed that SFN increases the vacuolar pH of yeast cells and that varying the vacuolar pH can alter the sensitivity of yeast cells to the drug. In fact, several mutations that lower the vacuolar pH in yeast actually made the cells resistant to SFN (SFNR). Finally, we show that human lung cancer cells with more acidic compartments are also SFNR suggesting that SFN's mechanism of action identified in yeast may carry over to higher eukaryotic cells.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 5","pages":"129-138"},"PeriodicalIF":4.6,"publicationDate":"2020-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37920938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Regulation of anti-microbial autophagy by factors of the complement system. 补体系统因子对抗微生物自噬的调控。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2020-03-19 DOI: 10.15698/mic2020.04.712

Christophe Viret, Aurore Rozières, Rémi Duclaux-Loras, Gilles Boschetti, Stéphane Nancey, Mathias Faure

{"title":"Regulation of anti-microbial autophagy by factors of the complement system.","authors":"Christophe Viret, Aurore Rozières, Rémi Duclaux-Loras, Gilles Boschetti, Stéphane Nancey, Mathias Faure","doi":"10.15698/mic2020.04.712","DOIUrl":"https://doi.org/10.15698/mic2020.04.712","url":null,"abstract":"The complement system is a major component of innate immunity that participates in the defense of the host against a myriad of pathogenic microorganisms. Activation of complement allows for both local inflammatory response and physical elimination of microbes through phagocytosis or lysis. The system is highly efficient and is therefore finely regulated. In addition to these well-established properties, recent works have revealed that components of the complement system can be involved in a variety of other functions including in autophagy, the conserved mechanism that allows for the targeting and degradation of cytosolic materials by the lysosomal pathway after confining them into specialized organelles called autophagosomes. Besides impacting cell death, development or metabolism, the complement factors-autophagy connection can greatly modulate the cell autonomous, anti-microbial activity of autophagy: xenophagy. Both surface receptor-ligand interactions and intracellular interactions are involved in the modulation of the autophagic response to intracellular microbes by complement factors. Here, we review works that relate to the recently discovered connections between factors of the complement system and the functioning of autophagy in the context of host-pathogen relationship.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 4","pages":"93-105"},"PeriodicalIF":4.6,"publicationDate":"2020-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37821932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids. 驱动力倍半萜类化合物的广谱抗真菌活性及其作用机制。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2020-03-12 DOI: 10.15698/mic2020.06.719

Edruce Edouarzin, Connor Horn, Anuja Paudyal, Cunli Zhang, Jianyu Lu, Zongbo Tong, Guri Giaever, Corey Nislow, Raja Veerapandian, Duy H Hua, Govindsamy Vediyappan

{"title":"Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids.","authors":"Edruce Edouarzin, Connor Horn, Anuja Paudyal, Cunli Zhang, Jianyu Lu, Zongbo Tong, Guri Giaever, Corey Nislow, Raja Veerapandian, Duy H Hua, Govindsamy Vediyappan","doi":"10.15698/mic2020.06.719","DOIUrl":"https://doi.org/10.15698/mic2020.06.719","url":null,"abstract":"Eight drimane sesquiterpenoids including (-)-drimenol and (+)-albicanol were synthesized from (+)-sclareolide and evaluated for their antifungal activities. Three compounds, (-)-drimenol, (+)-albicanol, and (1R,2R,4aS,8aS)-2-hydroxy-2,5,5,8a-tetramethyl-decahydronaphthalene-1-carbaldehyde (4) showed strong activity against C. albicans. (-)-Drimenol, the strongest inhibitor of the three, (at concentrations of 8 - 64 µg/ml, causing 100% death of various fungi), acts not only against C. albicans in a fungicidal manner, but also inhibits other fungi such as Aspergillus, Cryptococcus, Pneumocystis, Blastomyces, Saksenaea and fluconazole resistant strains of C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. auris. These observations suggest that drimenol is a broad-spectrum antifungal agent. At a high concentration (100 μg/ml) drimenol caused rupture of the fungal cell wall/membrane. In a nematode model of C. albicans infection, drimenol rescued the worms from C. albicans-mediated death, indicating drimenol is tolerable and bioactive in metazoans. Genome-wide fitness profiling assays of both S. cerevisiae (nonessential homozygous and essential heterozygous) and C. albicans (Tn-insertion mutants) collections revealed putative genes and pathways affected by drimenol. Using a C. albicans mutant spot assay, the Crk1 kinase associated gene products, Ret2, Cdc37, and orf19.759, orf19.1672, and orf19.4382 were revealed to be involved in drimenol's mechanism of action. The three orfs identified in this study are novel and appear to be linked with Crk1 function. Further, computational modeling results suggest possible modifications of the structure of drimenol, including the A ring, for improving the antifungal activity.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 6","pages":"146-159"},"PeriodicalIF":4.6,"publicationDate":"2020-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38052535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

More than flipping the lid: Cdc50 contributes to echinocandin resistance by regulating calcium homeostasis in Cryptococcus neoformans. 不仅仅是翻转盖子:Cdc50通过调节新生隐球菌的钙稳态来促进棘白菌素耐药性。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2020-02-20 DOI: 10.15698/mic2020.04.714

Chengjun Cao, Chaoyang Xue

{"title":"More than flipping the lid: Cdc50 contributes to echinocandin resistance by regulating calcium homeostasis in Cryptococcus neoformans.","authors":"Chengjun Cao, Chaoyang Xue","doi":"10.15698/mic2020.04.714","DOIUrl":"https://doi.org/10.15698/mic2020.04.714","url":null,"abstract":"Echinocandins are the newest fungicidal drug class approved for clinical use against common invasive mycoses. Yet, they are ineffective against cryptococcosis, predominantly caused by Cryptococcus neoformans. The underlying mechanisms of innate echinocandin resistance in C. neoformans remain unclear. We know that Cdc50, the β-subunit of the lipid translocase (flippase), mediates echinocandin resistance, as loss of the CDC50 gene sensitizes C. neoformans to caspofungin, a member of the echinocandins class. We sought to elucidate how Cdc50 facilitates caspofungin resistance by performing a forward genetic screen for cdc50Δ suppressor mutations that are caspofungin resistant. We identified a novel mechanosensitive calcium channel protein Crm1 that correlates with Cdc50 function (Cao et al., 2019). In addition to regulating phospholipid translocation, Cdc50 also interacts with Crm1 to regulate intracellular calcium homeostasis and calcium/calcineurin signaling that likely drives caspofungin resistance in C. neoformans. Our study revealed a novel dual function of Cdc50 that connects lipid flippase with calcium signaling. These unexpected findings provide new insights into the mechanisms of echinocandin resistance in C. neoformans that may drive future drug design.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 4","pages":"115-118"},"PeriodicalIF":4.6,"publicationDate":"2020-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37821934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Raman-based sorting of microbial cells to link functions to their genes. 基于拉曼的微生物细胞分类，将功能与其基因联系起来。

IF 4.1 3区生物学

Microbial Cell Pub Date : 2020-02-10 DOI: 10.15698/mic2020.03.709

Kang Soo Lee, Michael Wagner, Roman Stocker

引用次数: 0

Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae. 稳定和不稳定的绿色荧光蛋白报告器监测酿酒酵母菌钙调磷酸酶活性。

IF 4.1 3区生物学

Microbial Cell Pub Date : 2020-02-05 DOI: 10.15698/mic2020.04.713

Jutta Diessl, Arpita Nandy, Christina Schug, Lukas Habernig, Sabrina Büttner

{"title":"Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae.","authors":"Jutta Diessl, Arpita Nandy, Christina Schug, Lukas Habernig, Sabrina Büttner","doi":"10.15698/mic2020.04.713","DOIUrl":"10.15698/mic2020.04.713","url":null,"abstract":"The protein phosphatase calcineurin is activated in response to rising intracellular Ca2+ levels and impacts fundamental cellular processes in organisms ranging from yeast to humans. In fungi, calcineurin orchestrates cellular adaptation to diverse environmental challenges and is essential for virulence of pathogenic species. To enable rapid and large-scale assessment of calcineurin activity in living, unperturbed yeast cells, we have generated stable and destabilized GFP transcriptional reporters under the control of a calcineurin-dependent response element (CDRE). Using the reporters, we show that the rapid dynamics of calcineurin activation and deactivation can be followed by flow cytometry and fluorescence microscopy. This system is compatible with live/dead staining that excludes confounding dead cells from the analysis. The reporters provide technology to monitor calcineurin dynamics during stress and ageing and may serve as a drug-screening platform to identify novel antifungal compounds that selectively target calcineurin.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 4","pages":"106-114"},"PeriodicalIF":4.1,"publicationDate":"2020-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37821933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New insights in the mode of action of anti-leishmanial drugs by using chemical mutagenesis screens coupled to next-generation sequencing. 利用化学诱变筛选与新一代测序相结合，对抗利什曼原虫药物的作用模式有了新的认识。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2020-01-21 DOI: 10.15698/mic2020.02.708

Arijit Bhattacharya, Sophia Bigot, Prasad Kottayil Padmanabhan, Angana Mukherjee, Adriano Coelho, Philippe Leprohon, Barbara Papadopoulou, Marc Ouellette

{"title":"New insights in the mode of action of anti-leishmanial drugs by using chemical mutagenesis screens coupled to next-generation sequencing.","authors":"Arijit Bhattacharya, Sophia Bigot, Prasad Kottayil Padmanabhan, Angana Mukherjee, Adriano Coelho, Philippe Leprohon, Barbara Papadopoulou, Marc Ouellette","doi":"10.15698/mic2020.02.708","DOIUrl":"https://doi.org/10.15698/mic2020.02.708","url":null,"abstract":"Leishmania parasites are responsible for a range of clinical manifestations ranging from self-resolving cutaneous sores to life-threatening diseases. The management of leishmaniasis is complicated in part by the scarcity of treatment options but also by the emerging or established resistance to available drugs. A major driver of resistance in Leishmania is the amplification of resistance genes taking advantage of the highly repetitive genomic landscape of the parasite. The recent advent of whole genome gain of function screens gave new momentum to the study of such resistance mechanisms, leading to the identification of novel resistance factors and drug targets against approved drugs, which include antimony (SbIII), miltefosine (MIL), paromomycin (PMM), and amphotericin B. However, these screens do not pinpoint single nucleotide variations (SNVs), an important contributor of drug resistance. To fill the gap, our recent study describes the optimization of chemical mutagenesis coupled to next generation sequencing, an approach called Mut-seq, as a way to explore networks of drug resistance genes in organisms with a diploid to mosaic aneuploid genome like Leishmania. Our Mut-seq screen revealed associations between genes linked with lipid metabolism and resistance to MIL, and highlighted the role of a protein kinase in translation leading to resistance to PMM.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 2","pages":"59-61"},"PeriodicalIF":4.6,"publicationDate":"2020-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37615153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

The euchromatic histone mark H3K36me3 preserves heterochromatin through sequestration of an acetyltransferase complex in fission yeast. 在裂变酵母中，常染色组蛋白标记H3K36me3通过分离乙酰转移酶复合体来保存异染色质。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2020-01-03 DOI: 10.15698/mic2020.03.711

Paula R Georgescu, Matías Capella, Sabine Fischer-Burkart, Sigurd Braun

{"title":"The euchromatic histone mark H3K36me3 preserves heterochromatin through sequestration of an acetyltransferase complex in fission yeast.","authors":"Paula R Georgescu, Matías Capella, Sabine Fischer-Burkart, Sigurd Braun","doi":"10.15698/mic2020.03.711","DOIUrl":"https://doi.org/10.15698/mic2020.03.711","url":null,"abstract":"Maintaining the identity of chromatin states requires mechanisms that ensure their structural integrity through the concerted actions of histone modifiers, readers, and erasers. Histone H3K9me and H3K27me are hallmarks of repressed heterochromatin, whereas H3K4me and H3K36me are associated with actively transcribed euchromatin. Paradoxically, several studies have reported that loss of Set2, the methyltransferase responsible for H3K36me, causes de-repression of heterochromatin. Here we show that unconstrained activity of the acetyltransferase complex Mst2C, which antagonizes heterochromatin, is the main cause of the silencing defects observed in Set2-deficient cells. As previously shown, Mst2C is sequestered to actively transcribed chromatin via binding to H3K36me3 that is recognized by the PWWP domain protein Pdp3. We demonstrate that combining deletions of set2 + and pdp3 + results in an epistatic silencing phenotype. In contrast, deleting mst2 + , or other members of Mst2C, fully restores silencing in Set2-deficient cells. Suppression of the silencing defect in set2Δ cells is specific for pericentromeres and subtelomeres, which are marked by H3K9me, but is not seen for loci that lack genuine heterochromatin. Mst2 is known to acetylate histone H3K14 redundantly with the HAT Gnc5. Further, it is involved in the acetylation of the non-histone substrate and E3 ubiquitin ligase Brl1, resulting in increased H2B-K119 ubiquitylation at euchromatin. However, we reveal that none of these mechanisms are responsible for the Set2-dependent silencing pathway, implying that Mst2 targets another, unknown substrate critical for heterochromatin silencing. Our findings demonstrate that maintenance of chromatin states requires spatial constraint of opposing chromatin activities.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"7 3","pages":"80-92"},"PeriodicalIF":4.6,"publicationDate":"2020-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37729136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0