Microbial Cell最新文献_第7页

Lipid and fatty acid metabolism in trypanosomatids. 锥虫体内脂质和脂肪酸代谢。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-10-06 eCollection Date: 2021-11-01 DOI: 10.15698/mic2021.11.764

Giovana Parreira de Aquino, Marco Antonio Mendes Gomes, Roberto Köpke Salinas, Maria Fernanda Laranjeira-Silva

{"title":"Lipid and fatty acid metabolism in trypanosomatids.","authors":"Giovana Parreira de Aquino, Marco Antonio Mendes Gomes, Roberto Köpke Salinas, Maria Fernanda Laranjeira-Silva","doi":"10.15698/mic2021.11.764","DOIUrl":"https://doi.org/10.15698/mic2021.11.764","url":null,"abstract":"Trypanosomiases and leishmaniases are neglected tropical diseases that have been spreading to previously non-affected areas in recent years. Identification of new chemotherapeutics is needed as there are no vaccines and the currently available treatment options are highly toxic and often ineffective. The causative agents for these diseases are the protozoan parasites of the Trypanosomatidae family, and they alternate between invertebrate and vertebrate hosts during their life cycles. Hence, these parasites must be able to adapt to different environments and compete with their hosts for several essential compounds, such as amino acids, vitamins, ions, carbohydrates, and lipids. Among these nutrients, lipids and fatty acids (FAs) are essential for parasite survival. Trypanosomatids require massive amounts of FAs, and they can either synthesize FAs de novo or scavenge them from the host. Moreover, FAs are the major energy source during specific life cycle stages of T. brucei, T. cruzi, and Leishmania. Therefore, considering the distinctive features of FAs metabolism in trypanosomatids, these pathways could be exploited for the development of novel antiparasitic drugs. In this review, we highlight specific aspects of lipid and FA metabolism in the protozoan parasites T. brucei, T. cruzi, and Leishmania spp., as well as the pathways that have been explored for the development of new chemotherapies.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"8 11","pages":"262-275"},"PeriodicalIF":4.6,"publicationDate":"2021-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39736490","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

Urm1, not quite a ubiquitin-like modifier? Urm1，不是类似泛素的修饰剂?

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-09-21 eCollection Date: 2021-11-01 DOI: 10.15698/mic2021.11.763

Lars Kaduhr, Cindy Brachmann, Keerthiraju Ethiraju Ravichandran, James D West, Sebastian Glatt, Raffael Schaffrath

{"title":"Urm1, not quite a ubiquitin-like modifier?","authors":"Lars Kaduhr, Cindy Brachmann, Keerthiraju Ethiraju Ravichandran, James D West, Sebastian Glatt, Raffael Schaffrath","doi":"10.15698/mic2021.11.763","DOIUrl":"https://doi.org/10.15698/mic2021.11.763","url":null,"abstract":"Ubiquitin related modifier 1 (Urm1) is a unique eukaryotic member of the ubiquitin-fold (UbF) protein family and conserved from yeast to humans. Urm1 is dual-functional, acting both as a sulfur carrier for thiolation of tRNA anticodons and as a protein modifier in a lysine-directed Ub-like conjugation also known as urmylation. Although Urm1 conjugation coincides with oxidative stress and targets proteins like 2-Cys peroxiredoxins from yeast (Ahp1) and fly (Prx5), it was unclear how urmylation proceeds molecularly and whether it is affected by the activity of these antioxidant enzymes. An in-depth study of Ahp1 urmylation in yeast from our laboratory (Brachmann et al., 2020) uncovered that promiscuous lysine target sites and specific redox requirements determine the Urm1 acceptor activity of the peroxiredoxin. The results clearly show that the dimer interface and the 2-Cys based redox-active centers of Ahp1 are affecting the Urm1 conjugation reaction. Together with in vivo assays demonstrating that high organic peroxide concentrations can prevent Ahp1 from being urmylated, Brachmann et al. provide insights into a potential link between Urm1 utilization and oxidant defense of cells. Here, we highlight these major findings and discuss wider implications with regards to an emerging link between Urm1 conjugation and redox biology. Moreover, from these studies we propose to redefine our perspective on Urm1 and the molecular nature of urmylation, a post-translational conjugation that may not be that ubiquitin-like after all.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"8 11","pages":"256-261"},"PeriodicalIF":4.6,"publicationDate":"2021-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39895086","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: 1

Using microbial metalo-aminopeptidases as targets in human infectious diseases. 利用微生物金属氨基肽酶作为人类传染病的靶点。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-08-09 eCollection Date: 2021-10-04 DOI: 10.15698/mic2021.10.761

Jorge González-Bacerio, Maikel Izquierdo, Mirtha Elisa Aguado, Ana C Varela, Maikel González-Matos, Maday Alonso Del Rivero

引用次数: 3

The long and winding road of reverse genetics in Trypanosoma cruzi. 克氏锥虫反向遗传学之路漫长而曲折。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-08-05 eCollection Date: 2021-09-06 DOI: 10.15698/mic2021.09.758

Miguel A Chiurillo, Noelia Lander

{"title":"The long and winding road of reverse genetics in Trypanosoma cruzi.","authors":"Miguel A Chiurillo, Noelia Lander","doi":"10.15698/mic2021.09.758","DOIUrl":"https://doi.org/10.15698/mic2021.09.758","url":null,"abstract":"Trypanosomes are early divergent protists with distinctive features among eukaryotic cells. Together with Trypanosoma brucei and Leishmania spp., Trypanosoma cruzi has been one of the most studied members of the group. This protozoan parasite is the causative agent of Chagas disease, a leading cause of heart disease in the Americas, for which there is no vaccine or satisfactory treatment available. Understanding T. cruzi biology is crucial to identify alternative targets for antiparasitic interventions. Genetic manipulation of T. cruzi has been historically challenging. However, the emergence of CRISPR/Cas9 technology has significantly improved the ability to generate genetically modified T. cruzi cell lines. Still, the system alone is not sufficient to answer all biologically relevant questions. In general, current genetic methods have limitations that should be overcome to advance in the study of this peculiar parasite. In this brief historic overview, we highlight the strengths and weaknesses of the molecular strategies that have been developed to genetically modify T. cruzi, emphasizing the future directions of the field.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"8 9","pages":"203-207"},"PeriodicalIF":4.6,"publicationDate":"2021-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39420471","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: 8

Understanding the pathogenesis of infectious diseases by single-cell RNA sequencing. 通过单细胞RNA测序了解传染病的发病机制。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-08-04 eCollection Date: 2021-09-06 DOI: 10.15698/mic2021.09.759

Wanqiu Huang, Danni Wang, Yu-Feng Yao

引用次数: 7

Genome, transcriptome and secretome analyses of the antagonistic, yeast-like fungus Aureobasidium pullulans to identify potential biocontrol genes. 拮抗酵母样真菌普鲁兰金黄色葡萄球菌的基因组、转录组和分泌组分析，以确定潜在的生物防治基因。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-06-08 eCollection Date: 2021-08-02 DOI: 10.15698/mic2021.08.757

Maria Paula Rueda-Mejia, Lukas Nägeli, Stefanie Lutz, Richard D Hayes, Adithi R Varadarajan, Igor V Grigoriev, Christian H Ahrens, Florian M Freimoser

{"title":"Genome, transcriptome and secretome analyses of the antagonistic, yeast-like fungus Aureobasidium pullulans to identify potential biocontrol genes.","authors":"Maria Paula Rueda-Mejia, Lukas Nägeli, Stefanie Lutz, Richard D Hayes, Adithi R Varadarajan, Igor V Grigoriev, Christian H Ahrens, Florian M Freimoser","doi":"10.15698/mic2021.08.757","DOIUrl":"https://doi.org/10.15698/mic2021.08.757","url":null,"abstract":"Aureobasidium pullulans is an extremotolerant, cosmopolitan yeast-like fungus that successfully colonises vastly different ecological niches. The species is widely used in biotechnology and successfully applied as a commercial biocontrol agent against postharvest diseases and fireblight. However, the exact mechanisms that are responsible for its antagonistic activity against diverse plant pathogens are not known at the molecular level. Thus, it is difficult to optimise and improve the biocontrol applications of this species. As a foundation for elucidating biocontrol mechanisms, we have de novo assembled a high-quality reference genome of a strongly antagonistic A. pullulans strain, performed dual RNA-seq experiments, and analysed proteins secreted during the interaction with the plant pathogen Fusarium oxysporum. Based on the genome annotation, potential biocontrol genes were predicted to encode secreted hydrolases or to be part of secondary metabolite clusters (e.g., NRPS-like, NRPS, T1PKS, terpene, and β-lactone clusters). Transcriptome and secretome analyses defined a subset of 79 A. pullulans genes (among the 10,925 annotated genes) that were transcriptionally upregulated or exclusively detected at the protein level during the competition with F. oxysporum. These potential biocontrol genes comprised predicted secreted hydrolases such as glycosylases, esterases, and proteases, as well as genes encoding enzymes, which are predicted to be involved in the synthesis of secondary metabolites. This study highlights the value of a sequential approach starting with genome mining and consecutive transcriptome and secretome analyses in order to identify a limited number of potential target genes for detailed, functional analyses.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"8 8","pages":"184-202"},"PeriodicalIF":4.6,"publicationDate":"2021-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39313726","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: 10

LasR-regulated proteases in acute vs. chronic lung infection: a double-edged sword. 激光辐照调节的蛋白酶在急性和慢性肺部感染中的作用:一把双刃剑。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-05-31 eCollection Date: 2021-07-05 DOI: 10.15698/mic2021.07.755

Lisa C Hennemann, Dao Nguyen

{"title":"LasR-regulated proteases in acute vs. chronic lung infection: a double-edged sword.","authors":"Lisa C Hennemann, Dao Nguyen","doi":"10.15698/mic2021.07.755","DOIUrl":"https://doi.org/10.15698/mic2021.07.755","url":null,"abstract":"Pseudomonas aeruginosa is a gram-negative opportunistic pathogen capable of causing both acute and chronic infections, particularly in individuals with compromised host defenses. The quorum sensing transcriptional activator LasR is widely recognized for its role in regulating the expression of acute virulence factors, notably several secreted proteases which cause direct host damage and subvert host immunity in acute infections. Paradoxically, lung infections caused by LasR-deficient variants, which are found in at least a third of cystic fibrosis (CF) patients with chronic P. aeruginosa infections, are associated with accelerated lung disease and increased markers of inflammation compared to infections caused by strains with a functional LasR system. While the loss of LasR function often (although not always) results in impaired production of LasR-controlled acute virulence factors, the implication of this pathoadaptation on host-pathogen interactions and chronic disease pathology is less well recognized. We recently observed that loss of LasR function in lasR variants, which results in impaired secreted protease production, led to increased expression of the membrane-bound surface adhesion molecule mICAM-1 in the airway epithelium, and increased neutrophilic inflammation. Specifically, human airway epithelial cells stimulated with lasR variants had higher mICAM-1 expression and greater neutrophil binding in vitro compared to stimulation with wild-type P. aeruginosa. In a subacute non-lethal P. aeruginosa lung infection model, lasR variant infection also induced higher mICAM-1 expression in the murine airway epithelium and was associated with increased neutrophilic pulmonary inflammation in vivo. Here, we discuss how (loss of) LasR function and LasR-regulated proteases affect host immunity, inflammation and tissue pathology in acute vs. chronic P. aeruginosa lung infection.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"8 7","pages":"161-163"},"PeriodicalIF":4.6,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39174977","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

DNA polymerase III protein, HolC, helps resolve replication/transcription conflicts. DNA聚合酶III蛋白，HolC，有助于解决复制/转录冲突。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-05-06 DOI: 10.15698/mic2021.06.753

Susan T Lovett

{"title":"DNA polymerase III protein, HolC, helps resolve replication/transcription conflicts.","authors":"Susan T Lovett","doi":"10.15698/mic2021.06.753","DOIUrl":"https://doi.org/10.15698/mic2021.06.753","url":null,"abstract":"In Escherichia coli, DNA replication is catalyzed by an assembly of proteins, the DNA polymerase III holoenzyme. This complex includes the polymerase and proofreading subunits, the processivity clamp and clamp loader complex. The holC gene encodes an accessory protein (known as χ) to the core clamp loader complex and is the only protein of the holoenzyme that binds to single-strand DNA binding protein, SSB. HolC is not essential for viability although mutants show growth impairment, genetic instability and sensitivity to DNA damaging agents. In this study we isolate spontaneous suppressor mutants in a holCΔ strain and identify these by whole genome sequencing. Some suppressors are alleles of RNA polymerase, suggesting that transcription is problematic for holC mutant strains, and of sspA, stringent starvation protein. Using a conditional holC plasmid, we examine factors affecting transcription elongation and termination for synergistic or suppressive effects on holC mutant phenotypes. Alleles of RpoA (α), RpoB (β) and RpoC (β') RNA polymerase holoenzyme can partially suppress loss of HolC. In contrast, mutations in transcription factors DksA and NusA enhanced the inviability of holC mutants. HolC mutants showed enhanced sensitivity to bicyclomycin, a specific inhibitor of Rho-dependent termination. Bicyclomycin also reverses suppression of holC by rpoA, rpoC and sspA. An inversion of the highly expressed rrnA operon exacerbates the growth defects of holC mutants. We propose that transcription complexes block replication in holC mutants and Rho-dependent transcriptional termination and DksA function are particularly important to sustain viability and chromosome integrity.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"8 6","pages":"143-145"},"PeriodicalIF":4.6,"publicationDate":"2021-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39035094","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

Proanthocyanidin-enriched cranberry extract induces resilient bacterial community dynamics in a gnotobiotic mouse model. 原花青素丰富的蔓越莓提取物诱导弹性细菌群落动态在一个非生物小鼠模型。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-04-29 DOI: 10.15698/mic2021.06.752

Catherine C Neto, Benedikt M Mortzfeld, John R Turbitt, Shakti K Bhattarai, Vladimir Yeliseyev, Nicholas DiBenedetto, Lynn Bry, Vanni Bucci

{"title":"Proanthocyanidin-enriched cranberry extract induces resilient bacterial community dynamics in a gnotobiotic mouse model.","authors":"Catherine C Neto, Benedikt M Mortzfeld, John R Turbitt, Shakti K Bhattarai, Vladimir Yeliseyev, Nicholas DiBenedetto, Lynn Bry, Vanni Bucci","doi":"10.15698/mic2021.06.752","DOIUrl":"https://doi.org/10.15698/mic2021.06.752","url":null,"abstract":"Cranberry consumption has numerous health benefits, with experimental reports showing its anti-inflammatory and anti-tumor properties. Importantly, microbiome research has demonstrated that the gastrointestinal bacterial community modulates host immunity, raising the question of whether the cranberry-derived effect may be related to its ability to modulate the microbiome. Only a few studies have investigated the effect of cranberry products on the microbiome to date. Especially because cranberries are rich in dietary fibers, the extent of microbiome modulation by polyphenols, particularly proanthocyanidins (PACs), remains to be shown. Since previous work has only focused on long-term effects of cranberry extracts, in this study we investigated the effect of a water-soluble, PAC-rich cranberry juice extract (CJE) on the short-term dynamics of a human-derived bacterial community in a gnotobiotic mouse model. CJE characterization revealed a high enrichment in PACs (57%), the highest ever utilized in a microbiome study. In a 37-day experiment with a ten-day CJE intervention and 14-day recovery phase, we profiled the microbiota via 16S rRNA sequencing and applied diverse time-series analytics methods to identify individual bacterial responses. We show that daily administration of CJE induces distinct dynamic patterns in bacterial abundances during and after treatment, before recovering resiliently to pre-treatment levels. Specifically, we observed an increase of Akkermansia muciniphila and Clostridium hiranonis at the expense of Bacteroides ovatus after the offset of the selection pressure imposed by the PAC-rich CJE. This demonstrates that termination of an intervention with a cranberry product can induce changes of a magnitude as high as the intervention itself.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"8 6","pages":"131-142"},"PeriodicalIF":4.6,"publicationDate":"2021-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39035093","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: 10

Too much of a good thing: Overproduction of virulence factors impairs cryptococcal pathogenicity. 过量是件好事:毒力因子的过量产生会损害隐球菌的致病性。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-04-20 DOI: 10.15698/mic2021.05.750

Julia C V Reuwsaat, Tamara L Doering, Livia Kmetzsch

{"title":"Too much of a good thing: Overproduction of virulence factors impairs cryptococcal pathogenicity.","authors":"Julia C V Reuwsaat, Tamara L Doering, Livia Kmetzsch","doi":"10.15698/mic2021.05.750","DOIUrl":"https://doi.org/10.15698/mic2021.05.750","url":null,"abstract":"The regulation of virulence factor production and deployment is crucial for the establishment of microbial infection and subsequent pathogenesis. If these processes are not properly coordinated, the infecting pathogen is less likely to both survive the immune response and cause damage to the host. One key virulence factor of the opportunistic fungal pathogen Cryptococcus neoformans, which kills almost 200,000 people each year worldwide, is a polysaccharide capsule that surrounds the cell wall; this structure helps the fungal cells resist engulfment and elimination by host phagocytes. Another important virulence trait is the development of a giant (Titan) cell morphotype that increases fungal resistance to phagocytosis, oxidative stress, and antifungal treatment. We recently identified the transcription factor Pdr802 as essential for C. neoformans adaptation to and survival under host conditions both in vitro and in vivo (Reuwsaat et al., mBio, doi: 10.1128/mBio.03457-20). Cryptococci lacking Pdr802 display enlarged capsules and enhanced Titan cell production, along with dramatically reduced virulence in a mouse model of infection. These results demonstrate that more is not necessarily better when it comes to virulence factors. Instead, precise regulation of these traits, to avoid both under- and overexpression, is critical for the success of this pathogen as it faces the challenges imposed by the host environment.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"8 5","pages":"108-110"},"PeriodicalIF":4.6,"publicationDate":"2021-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38976006","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