Molecular Microbiology最新文献

{"title":"MecA: A Multifunctional ClpP-Dependent and Independent Regulator in Gram-Positive Bacteria","authors":"Zezhang T. Wen, Kassapa Ellepola, Hui Wu","doi":"10.1111/mmi.15356","DOIUrl":"https://doi.org/10.1111/mmi.15356","url":null,"abstract":"MecA is a broadly conserved adaptor protein in Gram-positive bacteria, mediating the recognition and degradation of specific target proteins by ClpCP protease complexes. MecA binds target proteins, often through recognition of degradation tags or motifs, and delivers them to the ClpC ATPase, which unfolds and translocates the substrates into the ClpP protease barrel for degradation. MecA activity is tightly regulated through interactions with ClpC ATPase and other factors, ensuring precise control over protein degradation and cellular homeostasis. Beyond proteolysis, emerging evidence highlights a ClpP-independent role of MecA in modulating the function of its targets, including key enzymes and transcriptional factors involved in biosynthetic and metabolic pathways. However, the full scope and mechanisms of ClpP-independent MecA regulation remain unclear, warranting further investigation.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"16 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin and gene regulation in archaea.","authors":"Fabian Blombach, Finn Werner","doi":"10.1111/mmi.15302","DOIUrl":"10.1111/mmi.15302","url":null,"abstract":"<p><p>The chromatinisation of DNA by nucleoid-associated proteins (NAPs) in archaea 'formats' the genome structure in profound ways, revealing both striking differences and analogies to eukaryotic chromatin. However, the extent to which archaeal NAPs actively regulate gene expression remains poorly understood. The dawn of quantitative chromatin mapping techniques and first NAP-specific occupancy profiles in different archaea promise a more accurate view. A picture emerges where in diverse archaea with very different NAP repertoires chromatin maintains access to regulatory motifs including the gene promoter independently of transcription activity. Our re-analysis of genome-wide occupancy data of the crenarchaeal NAP Cren7 shows that these chromatin-free regions are flanked by increased Cren7 binding across the transcription start site. While bacterial NAPs often form heterochromatin-like regions across islands with xenogeneic genes that are transcriptionally silenced, there is little evidence for similar structures in archaea and data from Haloferax show that the promoters of xenogeneic genes remain accessible. Local changes in chromatinisation causing wide-ranging effects on transcription restricted to one chromosomal interaction domain (CID) in Saccharolobus islandicus hint at a higher-order level of organisation between chromatin and transcription. The emerging challenge is to integrate results obtained at microscale and macroscale, reconciling molecular structure and function with dynamic genome-wide chromatin landscapes.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"218-231"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyphosphate: The \"Dark Matter\" of Bacterial Chromatin Structure.","authors":"Lisa R Racki, Lydia Freddolino","doi":"10.1111/mmi.15350","DOIUrl":"10.1111/mmi.15350","url":null,"abstract":"<p><p>Polyphosphate (polyP), broadly defined, consists of a chain of orthophosphate units connected by phosphoanhydride bonds. PolyP is the only universal inorganic biopolymer known to date and is present in all three domains of life. At a first approximation polyP appears to be a simple, featureless, and flexible polyanion. A growing body of evidence suggests that polyP is not as featureless as originally thought: it can form a wide variety of complexes and condensates through association with proteins, nucleic acids, and inorganic ions. It is becoming apparent that the emergent properties of the condensate superstructures it forms are both complex and dynamic. Importantly, growing evidence suggests that polyP can affect bacterial chromatin, both directly and by mediating interactions between DNA and proteins. In an increasing number of contexts, it is becoming apparent that polyP profoundly impacts both chromosomal structure and gene regulation in bacteria, thus serving as a rarely considered, but highly important, component in bacterial nucleoid biology.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"279-293"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo assembly of bacterial partition condensates on circular supercoiled and linear DNA.","authors":"Hicham Sekkouri Alaoui, Valentin Quèbre, Linda Delimi, Jérôme Rech, Roxanne Debaugny-Diaz, Delphine Labourdette, Manuel Campos, François Cornet, Jean-Charles Walter, Jean-Yves Bouet","doi":"10.1111/mmi.15297","DOIUrl":"10.1111/mmi.15297","url":null,"abstract":"<p><p>In bacteria, faithful DNA segregation of chromosomes and plasmids is mainly mediated by ParABS systems. These systems, consisting of a ParA ATPase, a DNA binding ParB CTPase, and centromere sites parS, orchestrate the separation of newly replicated DNA copies and their intracellular positioning. Accurate segregation relies on the assembly of a high-molecular-weight complex, comprising a few hundreds of ParB dimers nucleated from parS sites. This complex assembles in a multi-step process and exhibits dynamic liquid-droplet properties. Despite various proposed models, the complete mechanism for partition complex assembly remains elusive. This study investigates the impact of DNA supercoiling on ParB DNA binding profiles in vivo, using the ParABS system of the plasmid F. We found that variations in DNA supercoiling does not significantly affect any steps in the assembly of the partition complex. Furthermore, physical modeling, leveraging ChIP-seq data from linear plasmids F, suggests that ParB sliding is restricted to approximately 2 Kbp from parS, highlighting the necessity for additional mechanisms beyond ParB sliding over DNA for concentrating ParB into condensates nucleated at parS. Finally, explicit simulations of a polymer coated with bound ParB suggest a dominant role for ParB-ParB interactions in DNA compaction within ParB condensates.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"232-244"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification, characterization and classification of prokaryotic nucleoid-associated proteins.","authors":"Samuel Schwab, Remus T Dame","doi":"10.1111/mmi.15298","DOIUrl":"10.1111/mmi.15298","url":null,"abstract":"<p><p>Common throughout life is the need to compact and organize the genome. Possible mechanisms involved in this process include supercoiling, phase separation, charge neutralization, macromolecular crowding, and nucleoid-associated proteins (NAPs). NAPs are special in that they can organize the genome at multiple length scales, and thus are often considered as the architects of the genome. NAPs shape the genome by either bending DNA, wrapping DNA, bridging DNA, or forming nucleoprotein filaments on the DNA. In this mini-review, we discuss recent advancements of unique NAPs with differing architectural properties across the tree of life, including NAPs from bacteria, archaea, and viruses. To help the characterization of NAPs from the ever-increasing number of metagenomes, we recommend a set of cheap and simple in vitro biochemical assays that give unambiguous insights into the architectural properties of NAPs. Finally, we highlight and showcase the usefulness of AlphaFold in the characterization of novel NAPs.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"206-217"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Human-Specific miR-6762-5p Is an Activator of RhoA GTPase Enhancing Shigella flexneri Intercellular Spreading","authors":"Caroline Reisacher, Estelle Saifi, Elisabeth Ageron, Robert Theodor Mallmann, Norbert Klugbauer, David Skurnik, Laurence Arbibe","doi":"10.1111/mmi.15352","DOIUrl":"https://doi.org/10.1111/mmi.15352","url":null,"abstract":"MicroRNAs have recently emerged as major players in host –bacterial pathogen interactions, either as part of the host defense mechanism to neutralize infection or as a bacterial arsenal aimed at subverting host cell functions. Here, we identify the newly evolved human microRNA miR-6762-5p as a new player in the host–<i>Shigella</i> interplay. A microarray analysis in infected epithelial cells allowed the detection of this miRNA exclusively during the late phase of infection. Conditional expression of miR-6762-5p combined with a transcriptome analysis indicated a role in cytoskeleton remodeling. Likewise, miR-6762-5p enhanced stress fiber formation through RhoA activation, and <i>in silico</i> analysis identified several regulators of RhoA activity as potential direct transcriptional targets. We further showed that miR-6762-5p expression induces an increase in <i>Shigella</i> intercellular spreading, while miR-6762-5p inhibition reduced bacterial dissemination. We propose a model in which the expression of miR-6762-5p induces cytoskeleton modifications through RhoA activation to achieve a successful dissemination of <i>Shigella</i> in the host.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"51 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Bacterial Chromatin Proteins, Transcription, and DNA Topology: Inseparable Partners in the Control of Gene Expression”","authors":"","doi":"10.1111/mmi.15324","DOIUrl":"https://doi.org/10.1111/mmi.15324","url":null,"abstract":"","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"15 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future Directions of the Prokaryotic Chromosome Field","authors":"E. A. Abbondanzieri, A. B. Badrinarayanan, D. Barillà, S. D. Bell, F. Blombach, J. Y. Bouet, S. Bulgheresi, Q. A. D. Cao, R. T. Dame, C. Dekker, M. Demuysere, O. Espéli, P. C. M. Fogg, P. L. Freddolino, M. Ganji, T. M. Gerson, D. C. Grainger, L. W. Hamoen, J. Harju, A. Hocher, C. M. Hustmyer, J. K. Kaljevic, M. K. Karney, N. Kleckner, G. Laloux, R. Landick, V. S. Lioy, W. L. Liu, C. L. Liu, J. Mäkelä, A. S. Meyer, A. Noy, M. P. Pineau, K. Premrajka, L. R. Racki, F‐Z. M. Rashid, K. Schnetz, S. Schwab, M. Tišma, A. I. van der Sijs, T. van Heesch, R. van Raaphorst, J. Vreede, A. W. Walker, J‐C. Walter, S. C. Weber, P. A. Wiggins, H. J. Wing, J. Xiao, Z. Zhang","doi":"10.1111/mmi.15347","DOIUrl":"https://doi.org/10.1111/mmi.15347","url":null,"abstract":"In September 2023, the Biology and Physics of Prokaryotic Chromosomes meeting ran at the Lorentz Center in Leiden, The Netherlands. As part of the workshop, those in attendance developed a series of discussion points centered around current challenges for the field, how these might be addressed, and how the field is likely to develop over the next 10 years. The Lorentz Center staff facilitated these discussions via tools aimed at optimizing productive interactions. This Perspective article is a summary of these discussions and reflects the state‐of‐the‐art of the field. It is expected to be of help to colleagues in advancing their own research related to prokaryotic chromosomes and inspiring novel interdisciplinary collaborations. This forward‐looking perspective highlights the open questions driving current research and builds on the impressive recent progress in these areas as represented by the accompanying reviews, perspectives, and research articles in this issue. These articles underline the multi‐disciplinary nature of the field, the multiple length scales at which chromatin is studied in vitro and in and highlight the differences and similarities of bacterial and archaeal chromatin and chromatin‐associated processes.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"20 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NrdR in Streptococcus and Listeria spp.: DNA Helix Phase Dependence of the Bacterial Ribonucleotide Reductase Repressor","authors":"Saher Shahid, Mateusz Balka, Daniel Lundin, Daniel O. Daley, Britt‐Marie Sjöberg, Inna Rozman Grinberg","doi":"10.1111/mmi.15349","DOIUrl":"https://doi.org/10.1111/mmi.15349","url":null,"abstract":"NrdR is a universal transcriptional repressor of bacterial genes coding for ribonucleotide reductases (RNRs), essential enzymes that provide DNA building blocks in all living cells. Despite its bacterial prevalence, the NrdR mechanism has been scarcely studied. We report the biochemical, biophysical, and bioinformatical characterization of NrdR and its binding sites from two major bacterial pathogens of the phylum <jats:italic>Bacillota</jats:italic> <jats:styled-content style=\"fixed-case\"><jats:italic>Listeria monocytogenes</jats:italic></jats:styled-content> and <jats:styled-content style=\"fixed-case\"><jats:italic>Streptococcus pneumoniae</jats:italic></jats:styled-content>. NrdR consists of a Zn‐ribbon domain followed by an ATP‐cone domain. We show that it forms tetramers that bind to DNA when loaded with ATP and dATP, but if loaded with only ATP, NrdR forms various oligomeric complexes unable to bind DNA. The DNA‐binding site in <jats:styled-content style=\"fixed-case\"><jats:italic>L. monocytogenes</jats:italic></jats:styled-content> is a pair of NrdR boxes separated by 15–16 bp, whereas in <jats:styled-content style=\"fixed-case\"><jats:italic>S. pneumoniae</jats:italic></jats:styled-content>, the NrdR boxes are separated by unusually long spacers of 25–26 bp. This observation triggered a comprehensive binding study of four NrdRs from <jats:styled-content style=\"fixed-case\"><jats:italic>L. monocytogenes</jats:italic></jats:styled-content>, <jats:styled-content style=\"fixed-case\"><jats:italic>S. pneumoniae</jats:italic></jats:styled-content>, <jats:styled-content style=\"fixed-case\"><jats:italic>Escherichia coli</jats:italic></jats:styled-content>, and <jats:styled-content style=\"fixed-case\"><jats:italic>Streptomyces coelicolor</jats:italic></jats:styled-content> to a series of dsDNA fragments where the NrdR boxes were separated by 12–27 bp. The in vitro results were confirmed in vivo in <jats:styled-content style=\"fixed-case\"><jats:italic>E. coli</jats:italic></jats:styled-content> and revealed that NrdR binds most efficiently when there is an integer number of DNA turns between the center of the two NrdR boxes. The study facilitates the prediction of NrdR binding sites in bacterial genomes and suggests that the NrdR mechanism is conserved throughout the bacterial domain. It sheds light on RNR regulation in <jats:italic>Listeria</jats:italic> and <jats:italic>Streptococcus</jats:italic>, and since NrdR does not occur in eukaryotes, opens a way to the development of novel antibiotics.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"1 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homeostasis of Calnexin Is Essential for the Growth, Virulence, and Hypovirus RNA Accumulation in the Chestnut Blight Fungus","authors":"Tao Huang, Xiaoling Ma, Ziqi Zhao, Danna Qin, Weiye Qin, Jinzi Wang, Baoshan Chen, Xipu He","doi":"10.1111/mmi.15348","DOIUrl":"https://doi.org/10.1111/mmi.15348","url":null,"abstract":"Calnexin, a calcium-binding protein, promotes correct protein folding and prevents incompletely folded glycopolypeptides from premature oxidation and degradation. <i>Cryphonectria parasitica</i>, an ascomycete fungus responsible for chestnut blight, poses a significant threat to the chestnut forest or orchards worldwide. Although various aspects of calnexin have been investigated, little is known about the impact of fungal viruses. <i>CpCne</i> was identified and characterized in this study, encoding the calnexin in <i>C. parasitica</i>. Strains with deletion or interference of the <i>CpCne</i> gene had a significant reduction in biomass and pathogenicity, and strains with overexpression of the <i>CpCne</i> gene had retarded growth and reduced pathogenicity. Transcriptome analysis showed that the △<i>CpCne</i> mutant had significant changes in the expression of genes related to carbohydrate metabolism, cell wall polysaccharide synthesis and degradation, indicating that <i>CpCne</i> may reduce virulence by affecting the cell wall. Additionally, the △<i>CpCne</i> mutant was sensitive to endoplasmic reticulum (ER) stress, suggesting that <i>CpCne</i> plays an important role in maintaining ER homeostasis. Furthermore, <i>CpCne</i> was also involved in the interaction between <i>C. parasitica</i> and the CHV1-EP713. Deletion or overexpression of the <i>CpCne</i> gene reduced viral RNA accumulation, and deletion of the <i>CpCne</i> gene altered the lipid and carboxylic acid metabolic pathways, thereby interfering with virus replication and assembly. Together, we demonstrated that the homeostasis of calnexin in <i>C. parasitica</i> (CpCne) is essential for hyphal growth and virulence, and revealed its role in viral replication and virulence.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"19 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}