Microbial Cell最新文献_第6页

A roadmap for designing narrow-spectrum antibiotics targeting bacterial pathogens. 设计针对细菌病原体的窄谱抗生素的路线图。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2022-07-04 DOI: 10.15698/mic2022.07.780

Xinyun Cao, Robert Landick, Elizabeth A Campbell

{"title":"A roadmap for designing narrow-spectrum antibiotics targeting bacterial pathogens.","authors":"Xinyun Cao, Robert Landick, Elizabeth A Campbell","doi":"10.15698/mic2022.07.780","DOIUrl":"https://doi.org/10.15698/mic2022.07.780","url":null,"abstract":"Clostridioides difficile (Cdiff) infection (CDI) continues to be the leading threat of nosocomial deaths worldwide and a major burden on health-care systems. Broad-spectrum antibiotics eradicate the normal gut microbiome, killing protective commensal bacteria and increasing CDI recurrence. In contrast, Fidaxomicin (Fdx) is a narrow-spectrum antibiotic that inhibits Cdiff growth without affecting crucial gut microbes. However, the basis of the narrow-spectrum activity of Fdx on its target, RNA polymerase (RNAP), in Cdiff has been enigmatic. Recently, Cao et al. (Nature, doi: 10.1038/s41586-022-04545-z) combined transgenic RNAP design and synthesis with cryo-electron microscopy (cryo-EM) to identify a key determinant of Fdx inhibition of Cdiff RNAP. This finding was further corroborated by biochemical, bioinformatics, and genetic analysis. This microreview describes implications of this work for lineage-specific antibiotic design and new directions toward understanding transcription and regulation in Cdiff and other bacterial pathogens.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 7","pages":"136-138"},"PeriodicalIF":4.6,"publicationDate":"2022-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40606427","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

Breaking the clip for cargo unloading from motor proteins: mechanism and significance. 从运动蛋白上卸货的破夹:机制和意义。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2022-05-19 eCollection Date: 2022-06-06 DOI: 10.15698/mic2022.06.779

Keisuke Obara, Takumi Kamura

{"title":"Breaking the clip for cargo unloading from motor proteins: mechanism and significance.","authors":"Keisuke Obara, Takumi Kamura","doi":"10.15698/mic2022.06.779","DOIUrl":"https://doi.org/10.15698/mic2022.06.779","url":null,"abstract":"The mitochondrion is an essential organelle involved in ATP generation, lipid metabolism, regulation of calcium ions, etc. Therefore, it should be inherited properly by newly generated cells. In the budding yeast Saccharomyces cerevisiae, mitochondria are passed on to daughter cells by the motor protein, Myo2, on the actin cable. The mitochondria and Myo2 are connected via the adaptor protein Mmr1. After reaching daughter cells, mitochondria are released from the actin-myosin machinery and move dynamically. In our recent paper (Obara K et al. (2022), Nat Commun, doi:10.1038/s41467-022-29704-8), we demonstrated that the regulated proteolysis of Mmr1 is required for the unloading of mitochondria from Myo2 in daughter cells. Sequential post-translational modifications of Mmr1, i.e., phosphorylation followed by ubiquitination, are essential for Mmr1 degradation and mitochondrial release from Myo2. Defects in Mmr1 degradation cause stacking and deformation of mitochondria at the bud-tip and bud-neck, where Myo2 accumulates. Compared to wild-type cells, mutant cells with defects in Mmr1 degradation possess an elevated mitochondrial membrane potential and produce higher levels of reactive oxygen species (ROS), along with hypersensitivity to oxidative stress.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 6","pages":"133-135"},"PeriodicalIF":4.6,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9173699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40487328","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

Investigating the role of G-quadruplexes at Saccharomyces cerevisiae telomeres. 研究g -四联体在酿酒酵母端粒中的作用。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2022-05-19 eCollection Date: 2022-06-06 DOI: 10.15698/mic2022.06.778

Sonia Stinus, Fernando R Rosas Bringas, Lisa Wanders, Michael Chang

{"title":"Investigating the role of G-quadruplexes at Saccharomyces cerevisiae telomeres.","authors":"Sonia Stinus, Fernando R Rosas Bringas, Lisa Wanders, Michael Chang","doi":"10.15698/mic2022.06.778","DOIUrl":"https://doi.org/10.15698/mic2022.06.778","url":null,"abstract":"The G-quadruplex consensus motif G≥3NxG≥3NxG≥3NxG≥3 is found at telomeres of many species, ranging from yeast to plants to humans, but the biological significance of this fact remains largely unknown. In this study, we examine the in vivo relevance of telomeric G-quadruplexes in the budding yeast Saccharomyces cerevisiae by expressing a mutant telomerase RNA subunit (tlc1-tm) that introduces mutant [(TG)0-4TGG]xATTTGG telomeric repeats instead of wild-type (TG)0-6TGGGTGTG(G)0-1 repeats to the distal ends of telomeres. The tlc1-tm telomere sequences lack the GGG motif present in every wild-type repeat and, therefore, are expected to be impaired in the formation of G-quadruplexes. Circular dichroism analysis of oligonucleotides consisting of tlc1-tm telomeric sequence is consistent with this hypothesis. We have previously shown that tlc1-tm cells grow similarly to wild-type cells, suggesting that the ability to form telomeric G-quadruplexes is not essential for telomere capping in S. cerevisiae cells.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 6","pages":"126-132"},"PeriodicalIF":4.6,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9173700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40487329","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

A hundred spotlights on microbiology: how microorganisms shape our lives 聚焦微生物学:微生物如何塑造我们的生活

IF 4.6 3区生物学

Microbial Cell Pub Date : 2022-04-04 DOI: 10.15698/mic2022.04.773

D. Carmona-Gutierrez, Katharina Kainz, A. Zimmermann, Sebastian J. Hofer, M. Bauer, C. Ruckenstuhl, G. Kroemer, F. Madeo

引用次数: 0

Yeast goes viral: probing SARS-CoV-2 biology using S. cerevisiae 酵母病毒传播：利用酿酒酵母探索严重急性呼吸系统综合征冠状病毒2型生物学

IF 4.6 3区生物学

Microbial Cell Pub Date : 2022-03-21 DOI: 10.15698/mic2022.04.774

Brandon Ho, Raphaël Loll-Krippleber, Grant W. Brown

引用次数: 0

Pirates of the haemoglobin 血红蛋白海盗

IF 4.6 3区生物学

Microbial Cell Pub Date : 2022-02-18 DOI: 10.15698/mic2022.04.775

Daniel Akinbosede, Robert Chizea, S. Hare

{"title":"Pirates of the haemoglobin","authors":"Daniel Akinbosede, Robert Chizea, S. Hare","doi":"10.15698/mic2022.04.775","DOIUrl":"https://doi.org/10.15698/mic2022.04.775","url":null,"abstract":"Not all treasure is silver and gold; for pathogenic bacteria, iron is the most precious and the most pillaged of metallic elements. Iron is essential for the survival and growth of all life; however free iron is scarce for bacteria inside human hosts. As a mechanism of defence, humans have evolved ways to store iron so as to render it inaccessible for invading pathogens, such as keeping the metal bound to iron-carrying proteins. For bacteria to survive within humans, they must therefore evolve counters to this defence to compete with these proteins for iron binding, or directly steal iron from them. The most populous form of iron in humans is haem: a functionally significant coordination complex that is central to oxygen transport and predominantly bound by haemoglobin. Haemoglobin is therefore the largest source of iron in humans and, as a result, bacterial pathogens in critical need of iron have evolved complex and creative ways to acquire haem from haemoglobin. Bacteria of all cell wall types have the ability to bind haemoglobin at their cell surface, to accept the haem from it and transport this to the cytoplasm for downstream uses. This review describes the systems employed by various pathogenic bacteria to utilise haemoglobin as an iron source within human hosts and discusses their contribution to virulence.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 1","pages":"84 - 102"},"PeriodicalIF":4.6,"publicationDate":"2022-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44308874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Cleavage-defective Topoisomerase I mutants sharply increase G-quadruplex-associated genomic instability 切割缺陷的拓扑异构酶I突变体急剧增加G-四链体相关的基因组不稳定性

IF 4.6 3区生物学

Microbial Cell Pub Date : 2022-01-31 DOI: 10.15698/mic2022.03.771

Alexandra Berroyer, A. Bacolla, J. Tainer, Nayun Kim

{"title":"Cleavage-defective Topoisomerase I mutants sharply increase G-quadruplex-associated genomic instability","authors":"Alexandra Berroyer, A. Bacolla, J. Tainer, Nayun Kim","doi":"10.15698/mic2022.03.771","DOIUrl":"https://doi.org/10.15698/mic2022.03.771","url":null,"abstract":"Topoisomerase 1 (Top1) removes transcription-associated helical stress to suppress G4-formation and its induced recombination at genomic loci containing guanine-run containing sequences. Interestingly, Top1 binds tightly to G4 structures, and its inhibition or depletion can cause elevated instability at these genomic loci. Top1 is targeted by the widely used anti-cancer chemotherapeutic camptothecin (CPT) and its derivatives, which stabilize Top1 covalently attached on a DNA nick and prevent the re-ligation step. Here we investigated how CPT-resistance conferring Top1 mutants, which emerge in cancer patients and cells treated with CPT, affect G4-induced genomic instability in S. cerevisiae. We found that Top1 mutants form stable complexes with G4 DNA and that expression of Top1 cleavage-defective mutants but not a DNA-binding-defective mutant lead to significantly elevated instability at a G4-forming genomic locus. Elevated recombination rates were partly suppressed by their proteolytic removal by SPRTN homolog Wss1 SUMO-dependent metalloprotease in vivo. Furthermore, interaction between G4-DNA binding protein Nsr1, a homolog to clinically-relevant human nucleolin, and Top1 mutants lead to a synergistic increase in G4-associated recombination. These results in the yeast system are strengthened by our cancer genome data analyses showing that functionally detrimental mutations in Top1 correlate with an enrichment of mutations at G4 motifs. Our collective experimental and computational findings point to cooperative binding of Top1 cleavage-defective mutants and Nsr1 as promoting DNA replication blockage and exacerbating genomic instability at G4-motifs, thus complicating patient treatment.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 1","pages":"52 - 68"},"PeriodicalIF":4.6,"publicationDate":"2022-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44154065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

The small bowel microbiome changes significantly with age and aspects of the ageing process. 小肠微生物组随着年龄和衰老过程的各个方面发生显著变化。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-12-27 eCollection Date: 2022-01-03 DOI: 10.15698/mic2022.01.768

Gabriela Leite, Mark Pimentel, Gillian M Barlow, Ruchi Mathur

{"title":"The small bowel microbiome changes significantly with age and aspects of the ageing process.","authors":"Gabriela Leite, Mark Pimentel, Gillian M Barlow, Ruchi Mathur","doi":"10.15698/mic2022.01.768","DOIUrl":"https://doi.org/10.15698/mic2022.01.768","url":null,"abstract":"Gut microbiome changes have been associated with human ageing and implicated in age-related diseases including Alzheimer's disease and Parkinson's disease. However, studies to date have used stool samples, which do not represent the entire gut. Although more challenging to access, the small intestine plays critical roles in host metabolism and immune function. In this paper (Leite et al. (2021), Cell Reports, doi: 10.1016/j.celrep.2021.109765), we demonstrate significant differences in the small intestinal microbiome in older subjects, using duodenal aspirates from 251 subjects aged 18-80 years. Differences included significantly decreased microbial diversity in older subjects, driven by increased relative abundance of phylum Proteobacteria, particularly family Enterobacteriaceae and coliform genera Escherichia and Klebsiella. Moreover, while this decreased diversity was associated with the 'ageing process' (comprising chronologic age, number of medications, and number of concomitant diseases), changes in certain taxa were found to be associated with number of medications alone (Klebsiella), number of diseases alone (Clostridium, Bilophila), or chronologic age alone (Escherichia, Lactobacillus, Enterococcus). Lastly, many taxa associated with increasing chronologic age were anaerobes. These changes may contribute to changes in human health that occur during the ageing process.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 1","pages":"21-23"},"PeriodicalIF":4.6,"publicationDate":"2021-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39963974","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

Chromosome-condensed G1 phase yeast cells are tolerant to desiccation stress. 染色体凝聚的G1期酵母细胞对干燥胁迫具有耐受性。

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-11-26 eCollection Date: 2022-02-07 DOI: 10.15698/mic2022.02.770

Zhaojie Zhang, Gracie R Zhang

引用次数: 2

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its first variants in fourplex real-time quantitative reverse transcription-PCR assays. 四重实时定量逆转录- pcr检测严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)及其首批变异

IF 4.6 3区生物学

Microbial Cell Pub Date : 2021-11-25 eCollection Date: 2022-01-03 DOI: 10.15698/mic2022.01.767

Mathieu Durand, Philippe Thibault, Simon Lévesque, Ariane Brault, Alex Carignan, Louis Valiquette, Philippe Martin, Simon Labbé

{"title":"Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its first variants in fourplex real-time quantitative reverse transcription-PCR assays.","authors":"Mathieu Durand, Philippe Thibault, Simon Lévesque, Ariane Brault, Alex Carignan, Louis Valiquette, Philippe Martin, Simon Labbé","doi":"10.15698/mic2022.01.767","DOIUrl":"https://doi.org/10.15698/mic2022.01.767","url":null,"abstract":"The early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is required to identify and isolate contagious patients to prevent further transmission of SARS-CoV-2. In this study, we present a multitarget real-time TaqMan reverse transcription PCR (rRT-PCR) assay for the quantitative detection of SARS-CoV-2 and some of its circulating variants harboring mutations that give the virus a selective advantage. Seven different primer-probe sets that included probes containing locked nucleic acid (LNA) nucleotides were designed to amplify specific wild-type and mutant sequences in Orf1ab, Envelope (E), Spike (S), and Nucleocapsid (N) genes. Furthermore, a newly developed primer-probe set targeted human β2-microglobulin (B2M) as a highly sensitive internal control for RT efficacy. All singleplex and fourplex assays detected ≤ 14 copies/reaction of quantified synthetic RNA transcripts, with a linear amplification range of nine logarithmic orders. Primer-probe sets for detection of SARS-CoV-2 exhibited no false-positive amplifications with other common respiratory pathogens, including human coronaviruses NL63, 229E, OC43, and HKU-1. Fourplex assays were evaluated using 160 clinical samples positive for SARS-CoV-2. Results showed that SARS-CoV-2 viral RNA was detected in all samples, including viral strains harboring mutations in the Spike coding sequence that became dominant in the pandemic. Given the emergence of SARS-CoV-2 variants and their rapid spread in some populations, fourplex rRT-PCR assay containing four primer-probe sets represents a reliable approach to allow quicker detection of circulating relevant variants in a single reaction.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 1","pages":"1-20"},"PeriodicalIF":4.6,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39963973","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