Molecular Microbiology最新文献

{"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":"Polyphosphate: The \"Dark Matter\" of Bacterial Chromatin Structure.","authors":"Lisa R Racki, Lydia Freddolino","doi":"10.1111/mmi.15350","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellodextrin Metabolism and Phosphotransferase System-Catalyzed Uptake in Enterococcus faecalis.","authors":"Victor Combret, Isabelle Rincé, Ronan Cochelin, Florie Desriac, Cécile Muller, Diane Soussan, Axel Hartke, Josef Deutscher, Nicolas Sauvageot","doi":"10.1111/mmi.15346","DOIUrl":"https://doi.org/10.1111/mmi.15346","url":null,"abstract":"<p><p>Two PTS transporters involved in the uptake of cellobiose and short cellooligosaccharides were identified in Enterococcus faecalis. Genes coding for the different EII proteins are found in a locus composed of three operonic structures expressing two distinct EIIC (CelC1 and CelC2), two identical EIIB (CelB1 and CelB2) and a unique EIIA (CelA1). The EIIA plays a central role in β-glucoside uptake because it is required not only for β-homodiholosides but also for the diheteroside N-acetylglucosamine-L-asparagine. Depending on their size, cellooligosaccharides are preferably transported either by CelC1 (di-saccharides) or by CelC2 (4 glycosidic residues and more), with tri-saccharides being taken up by both EIIC transporters. Moreover, CelA1B2C2 require CelGHI to be functional, three small proteins, the function of which remains unknown. CelA1B1C1 is the main but not exclusive transporter of cellobiose and chitobiose. It is involved in the transport of other β-glucodisaccharides, such as laminaribiose and sophorose. This PTS can be complemented by other transporters highlighting the existence of a network for β-glucoside uptake. This locus is under the control of CelR, a LevR-like transcription activator.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414629","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}

{"title":"MmoD and MmoG Are Crucial for the Synthesis of Soluble Methane Monooxygenase in Methanotrophs","authors":"Minggen Cheng, Yongchuang Liu, Xin Yan","doi":"10.1111/mmi.15345","DOIUrl":"https://doi.org/10.1111/mmi.15345","url":null,"abstract":"Soluble methane monooxygenase (sMMO) from methanotrophs has been extensively investigated for decades. However, major knowledge gaps persist regarding the synthesis mechanism of sMMO, particularly concerning the ambiguous roles of <i>mmoD</i> and <i>mmoG</i> in the sMMO gene cluster. Here, the functions of <i>mmoD</i> and <i>mmoG</i> were investigated in a model methanotrophic strain, <i>Methylotuvimicrobium buryatense</i> 5GB1C. Both genes were found to be essential for the functional expression of sMMO. Genetic and biochemical data supported the hypothesis that MmoG acts as a folding chaperone for both MmoX and MmoR, while MmoD serves as an assembly chaperone for the hydroxylase component. The functional expression of sMMO in <i>Escherichia coli</i> was achieved in an <i>mmoD-</i> and <i>mmoG-</i>dependent manner. In addition, deletion of <i>mmoD</i> dramatically reduced the transcription of the sMMO cluster in <i>M. buryatense</i> 5GB1C, implying that MmoD may regulate the sMMO cluster via an unknown mechanism. Knockout of neither <i>mmoD</i> nor <i>mmoG</i> abolished the essential feature of “copper switch”, indicating that they do not serve as the initial regulators of “copper switch”. These results demonstrate the crucial roles of <i>mmoD</i> and <i>mmoG</i> in sMMO synthesis and offer new insights into heterologous expression of sMMO.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"1 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385800","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":"Remote Regulation by VirB, the Transcriptional Anti‐Silencer of Shigella Virulence Genes, Provides Mechanistic Information","authors":"Cody Cris, Monika M. A. Karney, Juniper S. Rosen, Alexander D. Karabachev, Elizabeth N. Huezo, Helen J. Wing","doi":"10.1111/mmi.15344","DOIUrl":"https://doi.org/10.1111/mmi.15344","url":null,"abstract":"Classical models of bacterial transcription show regulators binding close to promoter elements to exert their effect. However, the scope for long‐range regulation exists, especially by nucleoid structuring proteins, like H‐NS. Here, long‐range regulation by VirB, a transcriptional regulator that alleviates H‐NS‐mediated silencing of key virulence genes in <jats:italic>Shigella</jats:italic> species, is explored in vivo to test the limits of long‐range regulation and provide further mechanistic insight. VirB‐dependent regulation of the well‐characterized <jats:italic>icsP</jats:italic> promoter persists if its cognate site is repositioned 1 kb, 3.3 kb, and even 4.7 kb further upstream than its native position in a plasmid reporter. VirB‐dependent regulation diminishes with binding site distance. While increasing cellular VirB pools elevated promoter activity in all constructs with wild‐type VirB binding sites, it did not generate a disproportionate increase in promoter activity from remote sites relative to the native site. Since VirB occludes a constitutively active promoter (PT5) when docked adjacent to its −35 element, we next moved the VirB binding site far outside the promoter region. We discovered that VirB still interfered with promoter activity. These findings and those generated from molecular roadblocks engineered around a distally located VirB‐binding site are reconciled with the various models of transcriptional regulation by VirB.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"39 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192107","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":"Distinct but Redundant Roles of ER Cargo Receptors p24 and Erv29 in Facilitating Proper Secretion of Cellulases in Trichoderma reesei","authors":"Zhixing Wang, Lin Liu, Yi Pu, Yu Fang, Wenhao Lv, Weifeng Liu","doi":"10.1111/mmi.15343","DOIUrl":"https://doi.org/10.1111/mmi.15343","url":null,"abstract":"<i>Trichoderma reesei</i> represents an important industrial workhorse for (hemi)cellulase production. However, relatively little is known about the details of its secretory pathway ensuring the extremely high-level enzyme secretion and how they might be leveraged for engineering improved protein production. Here, the functions of <i>T. reesei</i> ER cargo receptors p24 and Erv29 in trafficking cellulase were characterised. Whereas individual deletion of <i>p24</i> or <i>erv29</i> resulted in only a marginal effect on extracellular cellulase secretion, distinct intracellular trafficking pathways exist for individual hydrolytic enzyme in <i>T. reesei</i>. Notably, the simultaneous absence of p24 and Erv29 abolished the secreted production of cellulases but not xylanases. The secretion defect was accompanied by an apparent intracellular accumulation of cellulases. Mutations of residues on the cytosolic side of p24 and Erv29 supposed to mediate COPII coat recognition also compromised cellulase secretion although the overall ER exit sites (ERES) formation did not seem to be affected. We further revealed that a VPL motif following the signal peptide of CBH2 necessitates its efficient secretion mediated by Erv29. These results indicate that two specific ER cargo receptors complement each other to mediate the proper intracellular trafficking of cellulases and thus ensuring their extracellular secretion.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"39 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077201","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}