microLife最新文献

{"title":"<i>Mycobacterium tuberculosis</i> infection triggers epigenetic changes that are enriched in a type I IFN signature.","authors":"Katrina Madden,&nbsp;Rayan El Hamra,&nbsp;Stefania Berton,&nbsp;Jake Felker,&nbsp;Gonzalo G Alvarez,&nbsp;Alexandre Blais,&nbsp;Jim Sun","doi":"10.1093/femsml/uqad006","DOIUrl":"https://doi.org/10.1093/femsml/uqad006","url":null,"abstract":"<p><p>Tuberculosis, a deadly infectious lung disease caused by <i>Mycobacterium tuberculosis</i> (Mtb), remains the leading cause of bacterial disease-related deaths worldwide. Mtb reprograms and disables key antibacterial response pathways, many of which are regulated by epigenetic mechanisms that control the accessibility of chromatin to the transcriptional machinery. Recent reports suggest that host phosphatases, such as PPM1A, contribute to regulating chromatin accessibility during bacterial infections. However, changes in genome-wide chromatin accessibility during Mtb infection and whether PPM1A plays a role in this process remains unknown. Herein, we use combinatorial chromatin accessibility (ATAC-seq) and transcriptomic (RNA-seq) profiling of wild-type, PPM1A knockout and PPM1A overexpressing macrophages to demonstrate that Mtb infection induces global chromatin remodelling consistent with changes in gene expression. The strongest concordant changes to chromatin accessibility and gene expression triggered by Mtb infection were enriched for genes involved in type I interferon (IFN) signalling pathways. A panel of 15 genes with the strongest concordant changes in chromatin accessibility and gene expression were validated to be significantly upregulated in Mtb-infected human monocyte-derived macrophages. PPM1A expression affects chromatin accessibility profiles during Mtb infection that are reflected in the total number, chromosome location, and directionality of change. Transcription factor binding motif analysis revealed enrichment for transcription factors involved in the type I IFN pathway during Mtb infection, including members of the IRF, MEF2, and AP-1 families. Our study shows that altered type I IFN responses in Mtb-infected macrophages occur due to genome-wide changes in chromatin accessibility, and that PPM1A could influence a subset of these signatures.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/35/uqad006.PMC9936219.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9317032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An archaeal Cas3 protein facilitates rapid recovery from DNA damage.","authors":"Guy Miezner,&nbsp;Israela Turgeman-Grott,&nbsp;Kelly M Zatopek,&nbsp;Andrew F Gardner,&nbsp;Leah Reshef,&nbsp;Deepak K Choudhary,&nbsp;Martina Alstetter,&nbsp;Thorsten Allers,&nbsp;Anita Marchfelder,&nbsp;Uri Gophna","doi":"10.1093/femsml/uqad007","DOIUrl":"https://doi.org/10.1093/femsml/uqad007","url":null,"abstract":"<p><p>CRISPR-Cas systems provide heritable acquired immunity against viruses to archaea and bacteria. Cas3 is a CRISPR-associated protein that is common to all Type I systems, possesses both nuclease and helicase activities, and is responsible for degradation of invading DNA. Involvement of Cas3 in DNA repair had been suggested in the past, but then set aside when the role of CRISPR-Cas as an adaptive immune system was realized. Here we show that in the model archaeon <i>Haloferax volcanii</i> a <i>cas3</i> deletion mutant exhibits increased resistance to DNA damaging agents compared with the wild-type strain, but its ability to recover quickly from such damage is reduced. Analysis of <i>cas3</i> point mutants revealed that the helicase domain of the protein is responsible for the DNA damage sensitivity phenotype. Epistasis analysis indicated that <i>cas3</i> operates with <i>mre11</i> and <i>rad50</i> in restraining the homologous recombination pathway of DNA repair. Mutants deleted for Cas3 or deficient in its helicase activity showed higher rates of homologous recombination, as measured in pop-in assays using non-replicating plasmids. These results demonstrate that Cas proteins act in DNA repair, in addition to their role in defense against selfish elements and are an integral part of the cellular response to DNA damage.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacteria without their phages are just not competitive.","authors":"Sarah Wettstadt","doi":"10.1093/femsml/uqac024","DOIUrl":"https://doi.org/10.1093/femsml/uqac024","url":null,"abstract":"As a veterinarian by training, José Penadés never thought he would stick with a scientific career. For his PhD, he already switched gears and worked on the human autoimmune disease Goodpasture syndrome. However, he quickly realised that studying autoantigens gave him quite a hard time and ‘immunology was just not [my] his thing’. Afterwards he decided to stay in Valencia, Spain, and get some teaching experience at a private school. Yet, here, he recognised that indeed he was missing research. So, José chose to go back to a previous lab where he could apply his newly acquired molecular biology toolbox to their project on bacterial biofilms. He focused on the Gram-positive Staphylococcus aureus and studied how this pathogen forms biofilms to persist in the host. He and his team found a new cell-wall associated protein that they called Bap for biofilm-associated protein showing that proteins are integral parts of bacterial biofilms (Cucarella et al. 2001). They discovered that S. aureus produces Bap and attaches it to its outer membrane as a sensor. Upon contact with a surface or another cell, for example during infection, Bap is cleaved off the bacterial membrane and released to the surrounding. During an inflammatory response in the human body, the pH of the local environment drops. This triggers the N-terminal amyloid-like regions of Bap to form aggregates that further become functional scaffolds of the biofilm matrix (Taglialegna et al. 2016). With this dip into the microbiology world, José was more determined and started to enjoy the scientific process. In comparison with immunological studies, he found microbiological experiments more rewarding, since ‘it is easier to see a phenotype. You can complement and move genes between bacteria as you like and you are pretty confident about the results that you see.’","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/fc/uqac024.PMC10117707.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of a logical regulatory network reveals how Fe-S cluster biogenesis is controlled in the face of stress.","authors":"Firas Hammami,&nbsp;Laurent Tichit,&nbsp;Béatrice Py,&nbsp;Frédéric Barras,&nbsp;Pierre Mandin,&nbsp;Elisabeth Remy","doi":"10.1093/femsml/uqad003","DOIUrl":"https://doi.org/10.1093/femsml/uqad003","url":null,"abstract":"<p><p>Iron-sulfur (Fe-S) clusters are important cofactors conserved in all domains of life, yet their synthesis and stability are compromised in stressful conditions such as iron deprivation or oxidative stress. Two conserved machineries, Isc and Suf, assemble and transfer Fe-S clusters to client proteins. The model bacterium <i>Escherichia coli</i> possesses both Isc and Suf, and in this bacterium utilization of these machineries is under the control of a complex regulatory network. To better understand the dynamics behind Fe-S cluster biogenesis in <i>E. coli</i>, we here built a logical model describing its regulatory network. This model comprises three biological processes: 1) Fe-S cluster biogenesis, containing Isc and Suf, the carriers NfuA and ErpA, and the transcription factor IscR, the main regulator of Fe-S clusters homeostasis; 2) iron homeostasis, containing the free intracellular iron regulated by the iron sensing regulator Fur and the non-coding regulatory RNA RyhB involved in iron sparing; 3) oxidative stress, representing intracellular H₂O₂ accumulation, which activates OxyR, the regulator of catalases and peroxidases that decompose H₂O₂ and limit the rate of the Fenton reaction. Analysis of this comprehensive model reveals a modular structure that displays five different types of system behaviors depending on environmental conditions, and provides a better understanding on how oxidative stress and iron homeostasis combine and control Fe-S cluster biogenesis. Using the model, we were able to predict that an <i>iscR</i> mutant would present growth defects in iron starvation due to partial inability to build Fe-S clusters, and we validated this prediction experimentally.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of second messengers in the regulation of cyanobacterial physiology: the carbon-concentrating mechanism and beyond.","authors":"Oliver Mantovani,&nbsp;Michael Haffner,&nbsp;Khaled A Selim,&nbsp;Martin Hagemann,&nbsp;Karl Forchhammer","doi":"10.1093/femsml/uqad008","DOIUrl":"https://doi.org/10.1093/femsml/uqad008","url":null,"abstract":"<p><p>Second messengers are a fundamental category of small molecules and ions that are involved in the regulation of many processes in all domains of life. Here we focus on cyanobacteria, prokaryotes playing important roles as primary producers in the geochemical cycles due to their capability of oxygenic photosynthesis and carbon and nitrogen fixation. Of particular interest is the inorganic carbon-concentrating mechanism (CCM), which allows cyanobacteria to concentrate CO₂ near RubisCO. This mechanism needs to acclimate toward fluctuating conditions, such as inorganic carbon availability, intracellular energy levels, diurnal light cycle, light intensity, nitrogen availability, and redox state of the cell. During acclimation to such changing conditions, second messengers play a crucial role, particularly important is their interaction with the carbon control protein SbtB, a member of the PII regulator protein superfamily. SbtB is capable of binding several second messengers, uniquely adenyl nucleotides, to interact with different partners in a variety of responses. The main identified interaction partner is the bicarbonate transporter SbtA, which is regulated via SbtB depending on the energy state of the cell, the light conditions, and different CO₂ availability, including cAMP signaling. The interaction with the glycogen branching enzyme, GlgB, showed a role for SbtB in the c-di-AMP-dependent regulation of glycogen synthesis during the diurnal life cycle of cyanobacteria. SbtB has also been shown to impact gene expression and metabolism during acclimation to changing CO₂ conditions. This review summarizes the current knowledge about the complex second messenger regulatory network in cyanobacteria, with emphasis on carbon metabolism.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogen vacuole membrane contact sites - close encounters of the fifth kind.","authors":"Simone Vormittag,&nbsp;Rachel J Ende,&nbsp;Isabelle Derré,&nbsp;Hubert Hilbi","doi":"10.1093/femsml/uqad018","DOIUrl":"https://doi.org/10.1093/femsml/uqad018","url":null,"abstract":"<p><p>Vesicular trafficking and membrane fusion are well-characterized, versatile, and sophisticated means of 'long range' intracellular protein and lipid delivery. Membrane contact sites (MCS) have been studied in far less detail, but are crucial for 'short range' (10-30 nm) communication between organelles, as well as between pathogen vacuoles and organelles. MCS are specialized in the non-vesicular trafficking of small molecules such as calcium and lipids. Pivotal MCS components important for lipid transfer are the VAP receptor/tether protein, oxysterol binding proteins (OSBPs), the ceramide transport protein CERT, the phosphoinositide phosphatase Sac1, and the lipid phosphatidylinositol 4-phosphate (PtdIns(4)<i>P</i>). In this review, we discuss how these MCS components are subverted by bacterial pathogens and their secreted effector proteins to promote intracellular survival and replication.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polarity of c-di-GMP synthesis and degradation.","authors":"Vanessa Kreiling,&nbsp;Kai M Thormann","doi":"10.1093/femsml/uqad014","DOIUrl":"https://doi.org/10.1093/femsml/uqad014","url":null,"abstract":"<p><p>The bacterial cell pole has long been recognized as a defined compartment for enzymatic activities that are important or even vital for the cell. Polarity of diguanylate cyclases and phosphodiesterases, enzymes that synthesize and degrade the second messenger c-di-GMP, has now been demonstrated for several bacterial systems. Here we review these polar regulatory systems and show how the asymmetry of c-di-GMP production and turnover in concert with different modes of activation and deactivation creates heterogeneity in cellular c-di-GMP levels. We highlight how this heterogeneity generates a diverse set of phenotypic identities or states and how this may benefit the cell population, and we discuss reasons why the polarity of c-di-GMP signaling is probably widespread among bacteria.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9545271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling evolution one nucleotide at a time.","authors":"Sarah Wettstadt","doi":"10.1093/femsml/uqad023","DOIUrl":"https://doi.org/10.1093/femsml/uqad023","url":null,"abstract":"Throughout her journey of becoming a microbiology researcher, Siv Andersson would change course every four or five years. ‘I usually just turn around, see what’s available and run off into the direction that looks most exciting, interesting, and challenging’. Every few years, important life decisions impacted her career and somehow paved her journey into academic research. After postdocs at the Laboratory of Molecular Biology in Cambridge and Columbia Medical School in New York, she became an Associate Professor at Uppsala University in 1997, where she had finished her Ph.D. Dissertation. In 2000, she became full Professor for Molecular Evolution and was Head of the Department of Evolution, Genomics, and Systematics at the Evolutionary Biology Centre from 2003 to 2009. Now being more open for long-term goals, Siv investigates how bacteria evolved throughout time; she even looked at time ranges of several million years. Siv and her group explored how two lineages of the bacterium Buchnera aphidicola adapted to their specific hosts, the pea aphid and the wheat aphid (Tamas et al. 2002). This endosymbiosis was established ∼150 million years ago, and the two lineages diverged ∼50–70 million years ago. Interestingly— and completely unexpectedly—they found that even though both lineages were living as endosymbionts with their respective hosts for such a long time, their gene contents barely differ. ‘When we looked at the gene maps and saw they were identical; we were just silent. And then the Ph.D. student started panicking because he thought the samples had been mixed up and the same bacterium had been sequenced twice.’ Later, they found that indeed a high degree of divergence was apparent at the nucleotide sequence level. Yet, no inversions, translocations, duplications, or gene acquisitions seemed to have happened throughout this extensive time period. With both endosymbionts having lost the genetic elements for a recombination machinery, their genome size and flexibility were reduced, which instead increased genome stability and left them with the same genomic architecture. As the next step, Siv aimed to understand the mechanisms of how B. aphidicola adapted to its aphid host (Tamas et al. 2008). This endosymbiont has one of the smallest and most A-T-rich bacterial genomes and some of its transcripts with poly(A) sequences contain frameshift mutations resulting in nonfunctional gene products. Yet, as Siv and her group found, transcriptional slippage of the polymerase can rescue these mutations and—against the odds—lead to functional gene products. Even though a seemingly inefficient mode of information processing, regulation mechanisms like these could be helpful in designing synthetic genomes.","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/bf/uqad023.PMC10132846.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(p)ppGpp - an important player during heat shock response.","authors":"Kristina Driller,&nbsp;Fabián A Cornejo,&nbsp;Kürşad Turgay","doi":"10.1093/femsml/uqad017","DOIUrl":"https://doi.org/10.1093/femsml/uqad017","url":null,"abstract":"<p><p>The alarmones and second messengers (p)ppGpp are important for the cellular response to amino acid starvation. Although the stringent response is present in many bacteria, the targets and functions of (p)ppGpp can differ between species, and our knowledge of (p)ppGpp targets is constantly expanding. Recently, it was demonstrated that these alarmones are also part of the heat shock response in <i>Bacillus subtilis</i> and that there is a functional overlap with the oxidative and heat stress transcriptional regulator Spx. Here, the (p)ppGpp second messenger alarmones allow the fast stress-induced downregulation of translation while Spx inhibits the further expression of translation-related genes to lower the load on the protein quality control system, while the chaperone and protease expression is induced. In this review, we discuss the role of (p)ppGpp and its intricate connections in the complex network of stress sensing, heat shock response, and adaptation in <i>B. subtilis</i> cells.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9545269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and functional diversity of bacterial cyclic nucleotide perception by CRP proteins.","authors":"Elizaveta Krol,&nbsp;Laura Werel,&nbsp;Lars Oliver Essen,&nbsp;Anke Becker","doi":"10.1093/femsml/uqad024","DOIUrl":"https://doi.org/10.1093/femsml/uqad024","url":null,"abstract":"<p><p>Cyclic AMP (cAMP) is a ubiquitous second messenger synthesized by most living organisms. In bacteria, it plays highly diverse roles in metabolism, host colonization, motility, and many other processes important for optimal fitness. The main route of cAMP perception is through transcription factors from the diverse and versatile CRP-FNR protein superfamily. Since the discovery of the very first CRP protein CAP in <i>Escherichia coli</i> more than four decades ago, its homologs have been characterized in both closely related and distant bacterial species. The cAMP-mediated gene activation for carbon catabolism by a CRP protein in the absence of glucose seems to be restricted to <i>E. coli</i> and its close relatives. In other phyla, the regulatory targets are more diverse. In addition to cAMP, cGMP has recently been identified as a ligand of certain CRP proteins. In a CRP dimer, each of the two cyclic nucleotide molecules makes contacts with both protein subunits and effectuates a conformational change that favors DNA binding. Here, we summarize the current knowledge on structural and physiological aspects of <i>E. coli</i> CAP compared with other cAMP- and cGMP-activated transcription factors, and point to emerging trends in metabolic regulation related to lysine modification and membrane association of CRP proteins.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/d8/uqad024.PMC10187061.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9570011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}