FEMS microbesPub Date : 2026-02-20eCollection Date: 2026-01-01DOI: 10.1093/femsmc/xtag011
Andrew J Sutherland-Smith, Vincenzo Carbone, Wiebke Kaziur-Cegla, Marion Woermann, Linley R Schofield, Ron S Ronimus
{"title":"Crystal structure of methanogen MtxX (Methanogen Marker Protein MMP4) from <i>Methanothermobacter thermautotrophicus</i> ΔH.","authors":"Andrew J Sutherland-Smith, Vincenzo Carbone, Wiebke Kaziur-Cegla, Marion Woermann, Linley R Schofield, Ron S Ronimus","doi":"10.1093/femsmc/xtag011","DOIUrl":"10.1093/femsmc/xtag011","url":null,"abstract":"<p><p>MtxX, also known as Methanogen Marker Protein 4 (MMP4), is a member of the group of proteins conserved in archaeal methanogens called the Methanogen Marker Proteins (MMPs). Owing to this taxonomic distribution the MMPs are presumed to have roles related to methanogenesis or are evidence for an evolutionary history associated with methanogenic processes. MtxX is sequence-annotated as either a methyltransferase (EC 2.1.1.-) or a phosphate acetyl/butyryltransferase (EC 2.3.1.8/2.3.1.19). Gene synteny analysis shows <i>mtxX</i> is located next to other MMP genes in Methanomicrobiales, Methanotrichales, and Methanocaldococcus genomes, while in Methanobacteria and Methanococci it is positioned adjacent to undecaprenyl pyrophosphate synthase, a cell wall biosynthesis enzyme. We describe the crystal structure for MtxX from <i>Methanothermobacter thermautotrophicus</i> ΔH showing that it has a protein fold homologous to phosphate acetyltransferases and decarboxylating NAD(P)-dependent dehydrogenases. The MtxX structure has a conserved binding cleft which is the presumptive functional site based on crystallographic symmetry-related molecular binding interactions and structural homology.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"7 ","pages":"xtag011"},"PeriodicalIF":4.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446078","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}
FEMS microbesPub Date : 2026-02-14eCollection Date: 2026-01-01DOI: 10.1093/femsmc/xtag009
Jeanette E Bröms, Igor Golovliov, Athar Alam, Shaochun Zhu, André Mateus, Thomas Henry, Anders Sjöstedt
{"title":"<i>Francisella tularensis</i> virulence relies on a conserved putative catalytic triad within the Type VI secretion system component PdpC.","authors":"Jeanette E Bröms, Igor Golovliov, Athar Alam, Shaochun Zhu, André Mateus, Thomas Henry, Anders Sjöstedt","doi":"10.1093/femsmc/xtag009","DOIUrl":"10.1093/femsmc/xtag009","url":null,"abstract":"<p><p>Gram-negative bacteria utilize type VI secretion systems (T6SS) for microbial competition and host interaction. While most pathogens rely on the canonical T6SS<sup>i</sup>, <i>Francisella</i> species uniquely possess T6SS<sup>ii</sup>. The highly virulent human pathogen <i>Francisella tularensis</i> harbors a distinct T6SS<sup>ii</sup> variant that includes <i>pdpC</i>, encoding a putative effector protein. Bioinformatic analysis revealed a conserved amino acid triad in PdpC, homologous to motifs found in Make Caterpillars Floppy family toxins. To investigate the functional relevance of this triad, site-directed mutagenesis was performed in the live vaccine strain of <i>F. tularensis</i>, substituting each residue with alanine. Mutants showed impaired phagosomal escape, reduced intracellular replication, and marked attenuation in the mouse infection model. Equivalent mutations introduced into <i>F. novicida</i>, a model for T6SS-mediated secretion, confirmed the triad's importance. Mass spectrometry analysis demonstrated that PdpC is secreted in a T6SS-dependent manner. Importantly, the mutations did not affect secretion, and deletion of <i>pdpC</i> did not alter the overall secretion profile. These findings indicate that the conserved triad is essential for PdpC's effector function but dispensable for its secretion. This study highlights a critical motif required for <i>Francisella</i> virulence and provides new insights into the specialized mechanisms of T6SS<sup>ii</sup> effectors.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"7 ","pages":"xtag009"},"PeriodicalIF":4.2,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12955703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357895","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}
FEMS microbesPub Date : 2026-02-09eCollection Date: 2026-01-01DOI: 10.1093/femsmc/xtag007
Rio Yamada, Hironobu Nakayama, Sumire Yoshikawa, Shuichi Karita, Midori Umekawa
{"title":"Uridine diphosphate <i>N</i>-acetylglucosamine homeostasis via CgNgk1 kinase modulates chitin levels and cell-wall integrity in <i>Candida glabrata</i>.","authors":"Rio Yamada, Hironobu Nakayama, Sumire Yoshikawa, Shuichi Karita, Midori Umekawa","doi":"10.1093/femsmc/xtag007","DOIUrl":"10.1093/femsmc/xtag007","url":null,"abstract":"<p><p><i>Candida glabrata</i> is a clinically significant cause of candidemia, yet how it supplies uridine diphosphate-<i>N</i>-acetylglucosamine (UDP-GlcNAc) for cell-wall chitin synthesis remains unclear. Here, we identify an <i>N</i>-acetylglucosamine (GlcNAc) kinase encoded by <i>CAGL0M00682g</i> and designated CgNgk1. <i>In vitro</i>, purified CgNgk1 preferentially phosphorylated GlcNAc with markedly higher catalytic efficiency than other sugars and accepted multiple nucleoside triphosphates, including ATP, as phosphoryl donors. Site-directed mutagenesis indicated that Asp197 and Lys155 are required for catalysis and ATP binding, respectively. <i>In vivo</i>, CgNgk1 overexpression in <i>C. glabrata</i> increased intracellular UDP-GlcNAc in a GlcNAc dose-dependent manner, whereas the kinase-dead D197N variant had no effect. CgNgk1-mediated GlcNAc phosphorylation elevated cell-wall chitin and heightened sensitivity to sodium dodecyl sulfate, heat, and low pH, but did not affect β-1,3-glucan-related phenotypes such as zymolyase or caspofungin sensitivity. Under GlcNAc supplementation, CgNgk1-overexpression specifically decreased cellular susceptibility to flucytosine, while responses to voriconazole and amphotericin B were unchanged. Overexpression of the putative hexosamine-pathway regulator CgIsr1 lowered intracellular UDP-GlcNAc, consistent with an intact endogenous pathway. These findings demonstrate that imported GlcNAc is routed via CgNgk1 to UDP-GlcNAc to promote chitin biosynthesis, and that quantitative control of this route shapes cell-wall integrity and modulates responses to host-relevant stresses and antifungal agents.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"7 ","pages":"xtag007"},"PeriodicalIF":4.2,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328392","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}
FEMS microbesPub Date : 2026-02-09eCollection Date: 2026-01-01DOI: 10.1093/femsmc/xtag008
Julio Cezar Fornazier Moreira, Flúvio Modolon, Natascha Menezes Bergo, Danilo Candido Vieira, Gustavo Fonseca, Francielli Vilela Peres, Rebeca Graciela Matheus Lizárraga, Diana Carolina Duque-Castaño, Alice de Moura Emilio, Augusto Miliorini Amendola, Renato Gamba Romano, Mateus Gustavo Chuqui, Fabiana S Paula, Daniel Leite Moreira, Célio Roberto Jonck, Amanda Bendia, Frederico Pereira Brandini, Vivian Helena Pellizari
{"title":"A machine learning approach elucidates spatial patterns of environmental properties driving microbial composition over Santos Basin, South Atlantic.","authors":"Julio Cezar Fornazier Moreira, Flúvio Modolon, Natascha Menezes Bergo, Danilo Candido Vieira, Gustavo Fonseca, Francielli Vilela Peres, Rebeca Graciela Matheus Lizárraga, Diana Carolina Duque-Castaño, Alice de Moura Emilio, Augusto Miliorini Amendola, Renato Gamba Romano, Mateus Gustavo Chuqui, Fabiana S Paula, Daniel Leite Moreira, Célio Roberto Jonck, Amanda Bendia, Frederico Pereira Brandini, Vivian Helena Pellizari","doi":"10.1093/femsmc/xtag008","DOIUrl":"10.1093/femsmc/xtag008","url":null,"abstract":"<p><p>Marine microbial communities are vital to biogeochemical cycling, yet their dynamics in regions of ecological and industrial significance, such as the Santos Basin (SB), Brazil's largest offshore oil-producing basin, remain poorly resolved. To address this gap, we combined 16S rRNA amplicon sequencing, flow cytometry, and a hybrid machine learning framework (Self-Organizing Maps and Random Forest) to analyze microbial community stratification across pelagic depths in the SB. We identified five depth-specific microbial associations predicted with 86% accuracy, driven primarily by temperature, salinity, water density, and nutrient availability. Shallow epipelagic and mesopelagic zones were dominated by temperature-driven assemblages, while deeper bathypelagic communities responded to salinity and density gradients. Temporal and spatial patterns further highlighted the influence of regional oceanographic processes, including the Cabo Frio upwelling and Rio de la Plata plume. Microbial diversity increased with depth, contrasting with higher cell abundances in nutrient-rich shallow waters. We provided new insights into the relative importance of oceanographic processes, suggesting that vertical stratification and regional hydrography may play a more central role shaping microbial communities than previously recognized. We also established a predictive framework for microbial dynamics in marine ecosystems, with direct implications for assessing anthropogenic impacts in industrially active regions like the SB.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"7 ","pages":"xtag008"},"PeriodicalIF":4.2,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147349860","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}
FEMS microbesPub Date : 2026-02-04eCollection Date: 2026-01-01DOI: 10.1093/femsmc/xtag003
Muhammad Talha, Cesar Augusto Roque-Borda
{"title":"Enhanced antibacterial activity of antimicrobial peptide-antibiotic combinations against multidrug-resistant bacteria.","authors":"Muhammad Talha, Cesar Augusto Roque-Borda","doi":"10.1093/femsmc/xtag003","DOIUrl":"10.1093/femsmc/xtag003","url":null,"abstract":"<p><p>The rapid emergence of multidrug-resistant (MDR) bacteria has severely compromised the efficacy of conventional antibiotics and intensified the global antimicrobial resistance crisis. Antimicrobial peptides (AMPs) have attracted considerable interest as adjunctive agents due to their membrane-active mechanisms and immunomodulatory properties; however, their clinical use as monotherapy remains limited by instability, toxicity, and pharmacokinetic constraints. Combining AMPs with conventional antibiotics has emerged as a promising strategy to enhance antibacterial efficacy, restore antibiotic susceptibility, and modulate resistance development. This review critically examines the mechanistic basis of AMP-antibiotic synergy, integrating evidence from <i>in vitro</i> and <i>in vivo</i> studies. Particular emphasis is placed on determinants that govern synergistic outcomes, including membrane permeability, porin-dependent antibiotic uptake, resistance-associated adaptations, and host-related factors that cannot be captured <i>in vitro</i>. In addition, we discuss key translational barriers limiting clinical implementation, such as immune modulation, pharmacokinetic mismatch, peptide instability, and strain-dependent variability in synergistic responses. By linking molecular mechanisms to experimental and translational outcomes, this review provides a focused framework for rational design and optimization of AMP-antibiotic combination therapies against MDR bacterial infections.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"7 ","pages":"xtag003"},"PeriodicalIF":4.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328436","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}
FEMS microbesPub Date : 2026-02-02eCollection Date: 2026-01-01DOI: 10.1093/femsmc/xtag006
Adit Naor, John Boothroyd
{"title":"<i>In vitro</i> growth of <i>Toxoplasma gondii</i> tachyzoites on different host cell lines selects for changes in efficiency of invasion and parasite surface antigen gene expression.","authors":"Adit Naor, John Boothroyd","doi":"10.1093/femsmc/xtag006","DOIUrl":"10.1093/femsmc/xtag006","url":null,"abstract":"<p><p><i>Toxoplasma gondii</i> is remarkable for its intermediate host range, which includes most warm-blooded animals so far tested. Being such a generalist poses challenges for how the parasite can be optimized for growth in cell types that might be radically different in their metabolism and other aspects, including host defenses and microenvironments. To explore how the parasite might adapt to finding itself in a different host, we started with a Type II line of <i>T. gondii</i> (ME49) that had been grown for at least the past 20 years exclusively <i>in vivo</i>. This line was then used to repeatedly infect two cell lines <i>in vitro</i>, human foreskin fibroblasts and Madin-Darby bovine kidney cells. After at least 70 such passages in one or other host cell type, the resulting lines were compared with respect to growth differences, secretion of an important adhesin (MIC2), and transcriptome. The results showed that passage on these two host cell lines results in profound and reproducible differences in parasite phenotype, including attachment/invasion, MIC2 secretion, and gene expression. The transcriptomic differences were especially pronounced for parasite surface antigen genes. The implications of these results for how <i>T. gondii</i> deals with its breadth of possible intermediate hosts are discussed.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"7 ","pages":"xtag006"},"PeriodicalIF":4.2,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12908928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215093","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}
FEMS microbesPub Date : 2026-01-22eCollection Date: 2026-01-01DOI: 10.1093/femsmc/xtag005
Wisnu Adi Wicaksono, Elma Zukancic, Matevz Zlatnar, Antonius Suwanto, Gabriele Berg
{"title":"Traditional fermented foods of Indonesia harbour functionally redundant but phylogenetically diverse taxa.","authors":"Wisnu Adi Wicaksono, Elma Zukancic, Matevz Zlatnar, Antonius Suwanto, Gabriele Berg","doi":"10.1093/femsmc/xtag005","DOIUrl":"10.1093/femsmc/xtag005","url":null,"abstract":"<p><p>Fermented foods represent complex microbial ecosystems that contribute to food quality, functionality, and potential health benefits, yet many traditional fermented foods remain poorly characterized. The aim of this study was to study microbial diversity, and functional potential of underexplored traditional Indonesian fermented food. The fermented products displayed substantial variation in bacterial richness, ranging from 65 to 614 bacterial amplicon sequence variants across samples. The microbial communities were dominated by bacterial taxa affiliated with the orders <i>Bacillales</i> and <i>Lactobacillales</i>, alongside fungal taxa from the order <i>Mucorales</i>. The plant-based products i.e. tape ketan and tape singkong had a higher bacterial abundance but lower diversity than animal-based terasi. We found significant correlations between bacterial and fungal communities dominated by positive cooccurrence patterns and highly complex networks especially in terasi. Each food product was characterized by a unique functional profile of genes linked to beneficial metabolic functions (biosynthesis of bacteriocins, short-chain fatty acids, and vitamins) but tape ketan samples demonstrated the highest diversity and abundance of them. Metagenome assembled genomes reflect a high diversity of health beneficial properties as well as substrate-specific degradation capabilities. Traditional Indonesian fermented foods harbour functionally redundant but phylogenetically diverse taxa offering a potential source for probiotic traits and functional food development.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"7 ","pages":"xtag005"},"PeriodicalIF":4.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12875122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144781","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}
FEMS microbesPub Date : 2026-01-22eCollection Date: 2026-01-01DOI: 10.1093/femsmc/xtag004
Eleonore Lebeuf-Taylor, Karl Cottenie
{"title":"Marginal link between sociality and gut microbiome in disparate mammalian hosts.","authors":"Eleonore Lebeuf-Taylor, Karl Cottenie","doi":"10.1093/femsmc/xtag004","DOIUrl":"10.1093/femsmc/xtag004","url":null,"abstract":"<p><p>Studies in model organisms and wild populations have uncovered manifold links between the gut microbiome and sociality, which, considering the adaptiveness of social behaviour, suggest a potentially generalized coevolution between microbiomes and social behaviour. Here, we leverage phylogenetically and ecologically diverse data from the Earth Microbiome Project to test the generality of the links between sociality and the gut microbiome in wild animals. We find evidence of a small but significant link between sociality and microbiome beta diversity, but not alpha diversity, in mammalian taxa, potentially due to socially mediated microbial transmission. Our work highlights the value of leveraging large-scale multi-study datasets to test fundamental questions about the role of sociality in host-microbiome coevolution.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"7 ","pages":"xtag004"},"PeriodicalIF":4.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12870121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127542","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}
FEMS microbesPub Date : 2026-01-10eCollection Date: 2026-01-01DOI: 10.1093/femsmc/xtag002
Elisabetha Larionova, Gary P Moran
{"title":"The role of <i>Fusobacterium nucleatum</i> in the tumour microenvironment and carcinogenesis of oral and colonic malignancies.","authors":"Elisabetha Larionova, Gary P Moran","doi":"10.1093/femsmc/xtag002","DOIUrl":"10.1093/femsmc/xtag002","url":null,"abstract":"<p><p>The intra-tumoural microbiome is an increasing area of research with potential benefits in cancer diagnostics and treatment development. Numerous studies have implicated <i>Fusobacterium nucleatum</i>, a member of the oral microbiota, in the development, immune evasion, and dissemination of oral and colorectal tumours. Although <i>F. nucleatum</i> is yet to be classified as a cause or consequence of cancer, reports indicate the microorganism's involvement in DNA damage, pathologic glucose uptake, and cellular proliferation. This accumulation of genetic instability is consistent with the multistep nature of malignant neoplasm progression. Virulence factors of <i>F. nucleatum</i> were shown to maintain an unresolved inflammatory state and impair the normal function of immune cells. The accompanying pro-inflammatory conditions facilitate vasculature remodelling, expediting tumour expansion, through a range of mechanisms. Pro-metastatic epithelial-to-mesenchymal transition and changes in gene expression have been observed in cancer cells upon <i>F. nucleatum</i> infection, suggesting an association with poorer prognosis. As a frequently encountered microorganism in the oral and colorectal intra-tumoural microbiome, <i>F. nucleatum</i> represents an intriguing, yet cautious research prospect with opportunities for novel prevention and therapeutic strategies. The objective of this work is to review the relevant evidence, taking into account the complexity of the tumour microenvironment.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"7 ","pages":"xtag002"},"PeriodicalIF":4.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109005","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}
FEMS microbesPub Date : 2026-01-06eCollection Date: 2026-01-01DOI: 10.1093/femsmc/xtag001
Alicia Reuzeau, Océane Reille, Soazig Malesinski, Frédéric Allemand, Tiffanie Barré, David Lemaire, Nathalie Sibille, Arjan de Groot, Laurence Blanchard
{"title":"Radiation-response in <i>Deinococcus</i> bacteria: characterization of the transient IrrE-DdrO heterodimer complex.","authors":"Alicia Reuzeau, Océane Reille, Soazig Malesinski, Frédéric Allemand, Tiffanie Barré, David Lemaire, Nathalie Sibille, Arjan de Groot, Laurence Blanchard","doi":"10.1093/femsmc/xtag001","DOIUrl":"10.1093/femsmc/xtag001","url":null,"abstract":"<p><p>Radiation resistance in <i>Deinococcus</i> requires an SOS-independent response mechanism, controlled by M78 family (COG2856) metallopeptidase IrrE and XRE family transcriptional repressor DdrO, to induce expression of DNA repair genes after exposure to radiation. DdrO must form dimers to bind target DNA sites. IrrE inactivates DdrO by cleaving the C-terminal dimerization domain of DdrO. However, the molecular basis of the interaction between IrrE and DdrO is still unknown. Here, we showed that IrrE is monomeric in solution and forms heterodimers with DdrO, with the N-terminal DNA-binding domain of DdrO contributing to the interaction. We further revealed that the initially isolated radiation-sensitive <i>irrE</i> mutant strain encodes an oxidation-sensitive IrrE protein affected in DdrO cleavage. Predicted COG2856/XRE regulatory protein pairs are present in many environmental, pathogenic, and industrial bacteria. Single-stranded DNA enhanced the cleavage activity of IrrE from <i>Deinococcus</i> as well as from closely related <i>Marinithermus</i> and <i>Oceanithermus</i> species, but not of the distant homologs ImmA from <i>Bacillus subtilis</i> and Rir from <i>Streptococcus thermophilus</i>. The formation of a heterotrimer containing IrrE, DdrO, and single-stranded DNA was also demonstrated. Together, these findings provide new insights into the molecular interplay between the key regulators IrrE and DdrO.</p>","PeriodicalId":73024,"journal":{"name":"FEMS microbes","volume":"7 ","pages":"xtag001"},"PeriodicalIF":4.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12828697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055232","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}