Marshall Jaroch, Kathryn Savage, Paul Kuipers, Jo Marie Bacusmo, Jennifer Hu, Jingjing Sun, Peter C. Dedon, Kelly C. Rice, Valérie de Crécy‐Lagard
{"title":"Environmental Control of Queuosine Levels in Streptococcus mutanstRNAs","authors":"Marshall Jaroch, Kathryn Savage, Paul Kuipers, Jo Marie Bacusmo, Jennifer Hu, Jingjing Sun, Peter C. Dedon, Kelly C. Rice, Valérie de Crécy‐Lagard","doi":"10.1111/mmi.15336","DOIUrl":"https://doi.org/10.1111/mmi.15336","url":null,"abstract":"Queuosine (Q) is a modification of the wobble base in tRNAs that decode NA(C/U) codons. It is ubiquitous in bacteria, including many pathogens. <jats:styled-content style=\"fixed-case\"><jats:italic>Streptococcus mutans</jats:italic></jats:styled-content> is an early colonizer of dental plaque biofilm and a key player in dental caries. Using a combination of genetic and physiological approaches, the predicted <jats:italic>Q</jats:italic> synthesis and salvage pathways were validated in this organism. These experiments confirmed that <jats:styled-content style=\"fixed-case\"><jats:italic>S. mutans</jats:italic></jats:styled-content> can synthesize <jats:italic>Q de novo</jats:italic> through similar pathways found in <jats:styled-content style=\"fixed-case\"><jats:italic>Bacillus subtilis</jats:italic></jats:styled-content> and <jats:styled-content style=\"fixed-case\"><jats:italic>Escherichia coli</jats:italic></jats:styled-content>. However, <jats:styled-content style=\"fixed-case\"><jats:italic>S. mutans</jats:italic></jats:styled-content> has a distinct salvage pathway compared to these model organisms, as it uses a transporter belonging to the energy coupling factor (ECF) family controlled by a preQ<jats:sub>1</jats:sub>‐dependent riboswitch. Furthermore, Q levels in this oral pathogen depended heavily on the media composition, suggesting that micronutrients can affect Q‐mediated translation efficiency.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"8 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884189","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":"Regulation of DNA Topology in Archaea: State of the Art and Perspectives","authors":"Paul Villain, Tamara Basta","doi":"10.1111/mmi.15328","DOIUrl":"https://doi.org/10.1111/mmi.15328","url":null,"abstract":"DNA topology is a direct consequence of the double helical nature of DNA and is defined by how the two complementary DNA strands are intertwined. Virtually every reaction involving DNA is influenced by DNA topology or has topological effects. It is therefore of fundamental importance to understand how this phenomenon is controlled in living cells. DNA topoisomerases are the key actors dedicated to the regulation of DNA topology in cells from all domains of life. While significant progress has been made in the last two decades in understanding how these enzymes operate in vivo in Bacteria and Eukaryotes, studies in Archaea have been lagging behind. This review article aims to summarize what is currently known about DNA topology regulation by DNA topoisomerases in main archaeal model organisms. These model archaea exhibit markedly different lifestyles, genome organization and topoisomerase content, thus highlighting the diversity and the complexity of DNA topology regulation mechanisms and their evolution in this domain of life. The recent development of functional genomic assays supported by next-generation sequencing now allows to delve deeper into this timely and exciting, yet still understudied topic.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"112 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870016","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":"ThyD Is a Thylakoid Membrane Protein Influencing Cell Division and Acclimation to High Light in the Multicellular Cyanobacterium Anabaena sp. Strain PCC 7120","authors":"Ana Valladares, Antonia Herrero","doi":"10.1111/mmi.15335","DOIUrl":"https://doi.org/10.1111/mmi.15335","url":null,"abstract":"Cyanobacteria developed oxygenic photosynthesis and represent the phylogenetic ancestors of chloroplasts. The model strain <i>Anabaena</i> sp. strain PCC 7120 grows as filaments of communicating cells and can form heterocysts, cells specialized for N<sub>2</sub> fixation. In the <i>Anabaena</i> genome, ORF all2390 is annotated as encoding a SulA homolog, but sequence similarity to SulA of model bacteria is insignificant. We generated strains that lacked or overexpressed all2390, both of which showed instances of increased cell size, and observed that purified All2390 protein interfered with the in vitro polymerization of FtsZ. Heterocyst frequency diminished by all2390 inactivation and increased by all2390 overexpression. Overexpression retarded the dismantlement of Z-ring structures that determines commitment in the differentiating cells. Thus, All2390 can influence cell division affecting heterocyst differentiation. An All2390-GFP fusion protein localized to the thylakoid membranes including the <i>honeycomb</i> membranes, which harbor photosynthetic complexes, in the heterocyst polar regions. Notably, all2390 expression strongly increased under high light, conditions under which growth of the null mutant is compromised. Thus, All2390 appears essential for adaptation to high light conditions. We named All2390 ThyD to reflect its thylakoidal localization and its dual role in cell division dynamics and acclimation of thylakoid membranes to increased light intensity.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"12 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763483","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}
Johannes Allweier, Michael Bartels, Hanifeh Torabi, Maria del Pilar Martinez Tauler, Nahla Galal Metwally, Thomas Roeder, Thomas Gutsmann, Iris Bruchhaus
{"title":"Cytoadhesion of Plasmodium falciparum-Infected Red Blood Cells Changes the Expression of Cytokine-, Histone- and Antiviral Protein-Encoding Genes in Brain Endothelial Cells","authors":"Johannes Allweier, Michael Bartels, Hanifeh Torabi, Maria del Pilar Martinez Tauler, Nahla Galal Metwally, Thomas Roeder, Thomas Gutsmann, Iris Bruchhaus","doi":"10.1111/mmi.15331","DOIUrl":"https://doi.org/10.1111/mmi.15331","url":null,"abstract":"Malaria remains a significant global health problem, mainly due to <i>Plasmodium falciparum</i>, which is responsible for most fatal infections. Infected red blood cells (iRBCs) evade spleen clearance by adhering to endothelial cells (ECs), triggering capillary blockage, inflammation, endothelial dysfunction and altered vascular permeability, prompting an endothelial transcriptional response. The iRBC<sup>IT4var04</sup>/HBEC-5i model, where iRBCs present IT4var04 (VAR2CSA) on their surface, was used to analyze the effects of iRBC binding on ECs at different temperature (37°C vs. 40°C). Binding of non-infected RBCs (niRBCs) and fever alone altered the expression of hundreds of genes in ECs. Comparing the expression profile of HBEC-5i cells cultured either in the presence of iRBCs or in the presence of niRBCs revealed significant upregulation of genes linked to immune response, nucleosome assembly, NF-kappa B signaling, angiogenesis, and antiviral immune response/interferon-alpha/beta signaling. Raising the temperature to 40°C, simulating fever, led to further upregulation of many genes, particularly those involved in cytokine production and angiogenesis. In summary, the presence of iRBCs stimulates ECs, activating several immunological pathways and affecting antiviral (−parasitic) mechanisms and angiogenesis. Our data uncovered the induction of the interferon-alpha/beta signaling pathway in ECs in response to iRBCs.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"262 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763484","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}
Christopher J. Presloid, Jialiu Jiang, Pratistha Kandel, Henry R. Anderson, Patrick C. Beardslee, Thomas M. Swayne, Karl R. Schmitz
{"title":"ClpS Directs Degradation of N-Degron Substrates With Primary Destabilizing Residues in Mycolicibacterium smegmatis","authors":"Christopher J. Presloid, Jialiu Jiang, Pratistha Kandel, Henry R. Anderson, Patrick C. Beardslee, Thomas M. Swayne, Karl R. Schmitz","doi":"10.1111/mmi.15334","DOIUrl":"https://doi.org/10.1111/mmi.15334","url":null,"abstract":"Drug-resistant tuberculosis infections are a major threat to global public health. The essential mycobacterial ClpC1P1P2 protease has received attention as a prospective target for novel antibacterial therapeutics. However, efforts to probe its function in cells are constrained by our limited knowledge of its physiological proteolytic repertoire. Here, we interrogate the role of mycobacterial ClpS in directing N-degron pathway proteolysis by ClpC1P1P2 in <i>Mycolicibacterium smegmatis</i>. Binding assays demonstrate that mycobacterial ClpS binds canonical primary destabilizing residues (Leu, Phe, Tyr, Trp) with moderate affinity. N-degron binding restricts the conformational flexibility of a loop adjacent to the ClpS N-degron binding pocket and strengthens ClpS•ClpC1 binding affinity ~30-fold, providing a mechanism for cells to prioritize N-degron proteolysis when substrates are abundant. Proteolytic reporter assays in <i>M. smegmatis</i> confirm degradation of substrates bearing primary N-degrons, but suggest that secondary N-degrons are absent in mycobacteria. This work expands our understanding of the mycobacterial N-degron pathway and identifies ClpS as a critical component for substrate specificity, providing insights that may support the development of improved Clp protease inhibitors.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"116 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763487","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":"Substrate Uptake by TonB-Dependent Outer Membrane Transporters","authors":"Volkmar Braun","doi":"10.1111/mmi.15332","DOIUrl":"https://doi.org/10.1111/mmi.15332","url":null,"abstract":"TonB is an essential component of an energy-generating system that powers active transport across the outer membrane (OM) of compounds that are too large or too scarce to diffuse through porins. The TonB-dependent OM transport proteins (TBDTs) consist of β barrels forming pores that are closed by plugs. The binding of TonB to TBDTs elicits plug movement, which opens the pores and enables nutrient translocation from the cell surface into the periplasm. TonB is also involved in the uptake of certain proteins, particularly toxins, through OM proteins that differ structurally from TBDTs. TonB binds to a sequence of five residues, designated as the TonB box, which is conserved in all TBDTs. Energy from the proton motive force (pmf) of the cytoplasmic membrane is transmitted to TonB by two proteins, ExbB and ExbD. These proteins form an energy-transmitting protein complex consisting of five ExbB proteins, forming a pore that encloses the ExbD dimer. This review discusses the structural changes that occur in TBDTs upon interaction with TonB, as well as the interaction of ExbB-ExbD with TonB, which is required to transmit the energy of the pmf and thereby open TBDT pores. TonB facilitates import of a wide range of substrates.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"13 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763486","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":"Uncovering the Significance of JNK/AKT Axis in the Autophagic Regulation of Leishmania major Infection","authors":"Vrushali Guhe, Shailza Singh","doi":"10.1111/mmi.15333","DOIUrl":"https://doi.org/10.1111/mmi.15333","url":null,"abstract":"The role of autophagy in host induced by infection of parasites of the <i>Leishmania</i> genus remains inadequately understood. <i>Leishmania</i> parasites modulate host macrophages to promote its survival by inducing autophagy response in the host cell. In this study, we conducted an investigation of <i>L. major</i> infection, focusing on host autophagy processes where we reconstructed two mathematical models elucidating autophagy induction and inhibition processes and its impact on parasite survival. Our models presented systems modulatory dynamics of the parasite-mediated host autophagy. Our work highlighted the pivotal role of signaling molecules associated with the immune response which included signaling induced by Toll-like receptor (TLR), specifically through regulation of JNK and AKT. Both molecules emerged as key regulators of host autophagy process, highlighting that JNK/AKT signaling axis may be a potential avenue for innovative therapeutic approaches in targeting leishmaniasis. Also, ATG16L complex was identified as a critical determinant in shaping the course of leishmanial infection through formation of autophagosomes. Through in vitro analyses in differentiated human monocyte cell line, we observed an increase in nitric oxide synthase (iNOS) concentration upon autophagy inhibition, while autophagy induction resulted in decreased iNOS concentration. This suggested that autophagy induction favors parasite survival in the host, potentially by providing a nutrient source that may be advantageous for the parasite. Inhibition of host autophagy promoted parasite elimination. Hence, our work proposed an avenue for strategically blocking host autophagy which enumerates a targeted approach for combating leishmaniasis.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"14 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763144","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}
Manon Vastel, Corinne Pau-Roblot, Séverine Ferré, Véronique Tocqueville, Chloé Ambroset, Corinne Marois-Créhan, Anne V Gautier-Bouchardon, Florence Tardy, Patrice Gaurivaud
{"title":"Capsular Polysaccharide Production in Bacteria of the Mycoplasma Genus: A Huge Diversity of Pathways and Synthases for So-Called Minimal Bacteria.","authors":"Manon Vastel, Corinne Pau-Roblot, Séverine Ferré, Véronique Tocqueville, Chloé Ambroset, Corinne Marois-Créhan, Anne V Gautier-Bouchardon, Florence Tardy, Patrice Gaurivaud","doi":"10.1111/mmi.15325","DOIUrl":"10.1111/mmi.15325","url":null,"abstract":"<p><p>Mycoplasmas are wall-less bacteria with many species spread across various animal hosts in which they can be pathogenic. Despite their reduced anabolic capacity, some mycoplasmas are known to secrete hetero- and homopolysaccharides, which play a role in host colonization through biofilm formation or immune evasion, for instance. This study explores how widespread the phenomenon of capsular homopolysaccharide secretion is within mycoplasmas, and investigates the diversity of both the molecules produced and the synthase-type glycosyltransferases responsible for their production. Fourteen strains representing 14 (sub)species from four types of hosts were tested in vitro for their polysaccharide secretion using both specific (immunodetection) and nonspecific (sugar dosage) assays. We evidenced a new, atypical homopolymer of β-(1 → 6)-glucofuranose (named glucofuranan) in the human pathogen Mycoplasma (M.) fermentans, as well as a β-(1 → 6)-glucopyranose polymer for the turkey pathogen M. iowae and galactan (β-(1 → 6)-galactofuranose) and β-(1 → 2)-glucopyranose for M. bovigenitalium infecting ruminants. Sequence and phylogenetic analyses revealed a huge diversity of synthases from varied Mycoplasma species. The clustering of these membrane-embedded glycosyltransferases into three main groups was only partially correlated to the structure of the produced homopolysaccharides.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"866-878"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546490","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 Complex and Challenging World of the Host–Pathogen Interaction","authors":"Marcel I. Ramirez","doi":"10.1111/mmi.15310","DOIUrl":"https://doi.org/10.1111/mmi.15310","url":null,"abstract":"","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"6 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697063","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}
Federico Matías Muzio, Corri D. Hamilton, Paolo Stincone, Betina Agaras, Cara H. Haney, Daniel Petras, Claudio Valverde
{"title":"Comparative Multi-Omics Survey Reveals Novel Specialized Metabolites and Biosynthetic Gene Clusters Under GacS Control in Pseudomonas donghuensis Strain SVBP6","authors":"Federico Matías Muzio, Corri D. Hamilton, Paolo Stincone, Betina Agaras, Cara H. Haney, Daniel Petras, Claudio Valverde","doi":"10.1111/mmi.15329","DOIUrl":"https://doi.org/10.1111/mmi.15329","url":null,"abstract":"In <i>Pseudomonas donghuensis</i> SVBP6, isolated from an agricultural field, the well-conserved Gac-Rsm pathway upregulates biosynthesis of the antifungal compound 7-hydroxytropolone (7-HT). However, 7-HT does not fully explain the strain's Gac-Rsm-dependent antimicrobial activity. Here, we combined comparative transcriptomic, proteomic, and metabolomic approaches to identify novel GacS-dependent biosynthetic gene clusters (BGC) and/or extracellular specialized metabolites. Our data revealed a broad impact of GacS on gene expression and extracellular metabolite profile of SVBP6. At both the mRNA and polypeptide levels, specialized metabolism was the main affected functional category in the <i>gacS</i> mutant. The major extracellular MS/MS spectral families promoted by GacS were fatty acid amides, fatty acids, and alkaloids. GacS was required for the production of the antimicrobial compound pseudoiodinine and to activate expression of the corresponding BGC. We also detected GacS-dependent production of 2,3,4-trihydro-β-carboline-1-one, which may add to the antimicrobial arsenal of SVBP6. Furthermore, transcriptomics and proteomics pinpointed several GacS-activated BGCs that had escaped <i>in silico</i> genome mining tools. Altogether, comparative multi-omics analyses of <i>gacS</i> loss-of-function mutants in <i>Pseudomonas</i> isolates are a promising strategy to uncover bioactive metabolites and/or their BGCs. Discovery of novel natural products is important for harnessing the potential of microbiota to improve crop plant growth and health.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"16 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637584","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}