microLifePub Date : 2026-09-23eCollection Date: 2026-01-01DOI: 10.1093/femsml/uqag036
Marion Lemarignier, Cyril Savin, Inés Ruedas-Torres, Anne Derbise, Charles Coluzzi, Jose Pablo Marin-Obando, Josue Barquero-Chavarria, Pierre Lê-Bury, Julien Burlaud-Gaillard, Julien Madej, Rémi Beau, Philippe Roingeard, Pierre Lechat, Eduardo P C Rocha, Jaime Gómez-Laguna, Javier Pizarro-Cerdá
{"title":"A putative type IVB secretion system contributes to the pathogenicity of <i>Yersinia pseudotuberculosis</i> lineage 8 strains associated with the Far East scarlet-like fever.","authors":"Marion Lemarignier, Cyril Savin, Inés Ruedas-Torres, Anne Derbise, Charles Coluzzi, Jose Pablo Marin-Obando, Josue Barquero-Chavarria, Pierre Lê-Bury, Julien Burlaud-Gaillard, Julien Madej, Rémi Beau, Philippe Roingeard, Pierre Lechat, Eduardo P C Rocha, Jaime Gómez-Laguna, Javier Pizarro-Cerdá","doi":"10.1093/femsml/uqag036","DOIUrl":"https://doi.org/10.1093/femsml/uqag036","url":null,"abstract":"<p><p><i>Yersinia pseudotuberculosis</i> is a food-borne pathogen responsible for a self-limiting mesenteric lymphadenitis. <i>Yersinia pseudotuberculosis</i> lineages 1 and 8 are also associated to the Far East scarlet-like fever (FESLF) syndrome, characterized by skin rash, hyperemic tongue, and desquamation. Genome sequencing of lineage 8 FESLF strains previously revealed the presence in the plasmid pVM82 of <i>dot/icm</i> genes, homologous to those known to encode a Type 4B Secretion System (T4BSS) in the intracellular pathogens <i>Legionella pneumophila</i> and <i>Coxiella burnetii</i>. We validated the presence of all essential <i>dot/icm</i> genes required for the structure of a T4BSS and we identified acidic pH and 37°C as the main signals triggering <i>y</i>T4BSS expression. Putative <i>y</i>T4BSS effectors were also identified using the S4TE algorithm but their secretion was not confirmed in the studied conditions. The <i>y</i>T4BSS is also expressed in epithelial cells and macrophages as well as <i>in vivo</i> during mouse infection, but it is not required for bacterial intracellular survival. Nevertheless, the <i>y</i>T4BSS is implicated in <i>Y. pseudotuberculosis</i> FESLF pathogenicity in mice when bacteria are orally inoculated. The <i>y</i>T4BSS does not influence organ colonization and is rather implicated in the induction of important necrosis lesions in mesenteric lymph nodes and ceca of mice. Cytokine profile analyses in mouse bone marrow-derived macrophages revealed a <i>y</i>T4BSS-dependent induction of innate immunity related cytokines and chemokines. In conclusion, we identify the <i>y</i>T4BSS as a virulence factor of <i>Y. pseudotuberculosis</i> strains from lineage 8 responsible for FESLF which modulates cytokine responses of the host innate immune system.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"7 ","pages":"uqag036"},"PeriodicalIF":0.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198295","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}
microLifePub Date : 2026-09-21eCollection Date: 2026-01-01DOI: 10.1093/femsml/uqag035
Eleonora Moratto, Emily Masters-Clark, Amelia J Clark, Aliya Pachmann, Cameron W M Murphy, Saskia Bindschedler, Pilar Junier, Claire E Stanley
{"title":"A microfluidic platform reveals the role of liquid movement on the dispersal of <i>Pseudomonas putida</i> via <i>Pythium ultimum</i> hyphal highways.","authors":"Eleonora Moratto, Emily Masters-Clark, Amelia J Clark, Aliya Pachmann, Cameron W M Murphy, Saskia Bindschedler, Pilar Junier, Claire E Stanley","doi":"10.1093/femsml/uqag035","DOIUrl":"https://doi.org/10.1093/femsml/uqag035","url":null,"abstract":"<p><p>Hyphal networks contribute to the connectivity between discrete soil microbial populations by providing a physical network through unsaturated soil matrixes. This network serves as a scaffold for bacteria to disperse and access previously isolated spaces via the 'fungal highway'. As bacteria require a liquid film for flagellar swimming, liquid saturation is a significant limiting factor for their dispersal in soil. The current working hypothesis is that bacteria can utilize thin liquid films associated with fungal or fungal-like hyphae to cross air gaps in soil environments. Studying these interactions at the microbial scale, however, is challenging due to the complex and stochastic 'black box' nature of soil environments. Hence, the microfluidic Hyphal Highways Device was developed to accomplish long-term quantification of bacterial dispersal along hyphal networks at single-cell level. Key findings highlight that <i>Pythium ultimum</i> is essential for <i>Pseudomonas putida</i> movement across an unsaturated environment, with mycelial biomass and liquid transport being key factors influencing bacterial dispersal. Additionally, <i>P. putida</i> actively modified the distribution of the transported liquid, increasing liquid patch connectivity. The Hyphal Highways Device provided quantitative insights into hyphal-mediated bacterial dispersal, opening new opportunities to study microscale interactions that shape microbial dynamics in natural and agricultural soils.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"7 ","pages":"uqag035"},"PeriodicalIF":0.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119670","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}
microLifePub Date : 2026-09-12eCollection Date: 2026-01-01DOI: 10.1093/femsml/uqag034
Simranpreet Kaur, Anna Katharina Renner, Pauline Porschitz, Franziska Schmidt, Svenja Grau, Hannah Afolayan, Stanislaw Schmidt, Thomas Lehrnbecher-Lanzeni, Hubertus Haas, Axel A Brakhage, Marc Thilo Figge, Marie von Lilienfeld-Toal, Zoltan Cseresnyés, Susann Hartung, Susanne Jahreis
{"title":"Reconstructing host-pathogen interactions: analysis of the intercellular network of macrophages and other immune cells within an aspergillosis-on-chip model.","authors":"Simranpreet Kaur, Anna Katharina Renner, Pauline Porschitz, Franziska Schmidt, Svenja Grau, Hannah Afolayan, Stanislaw Schmidt, Thomas Lehrnbecher-Lanzeni, Hubertus Haas, Axel A Brakhage, Marc Thilo Figge, Marie von Lilienfeld-Toal, Zoltan Cseresnyés, Susann Hartung, Susanne Jahreis","doi":"10.1093/femsml/uqag034","DOIUrl":"10.1093/femsml/uqag034","url":null,"abstract":"<p><p>The human-pathogenic fungus <i>Aspergillus fumigatus</i> can cause life-threatening infections, particularly in immunosuppressed or neutropenic patients with hematological malignancies. The human antifungal immune response primarily relies on neutrophils with contribution from macrophages, while the roles of unconventional lymphocytes such as Natural Killer (NK) cells and mucosal-associated invariant T (MAIT) cells remain less understood. Therefore, using an advanced microfluidic \"invasive aspergillosis-on-chip\" (IAC) model, we investigated the coordinated antifungal response of various immune cell types in combination with macrophages within a human tissue-like 3D environment. The IAC model, initially incorporating monocyte-derived macrophages, was enhanced by perfusing either primary neutrophils, NK cells, or MAIT cells for overnight infection experiments. In this model, hyphal growth of <i>A. fumigatus</i> was prevented only when both macrophages and neutrophils were present. However, uncontrolled growth was detected in neutropenic patient scenarios. We observed key interactions such as conidial shuttling and metaforosis between innate immune cells, accompanied by elevated cytokine levels of e.g. IL-1β and TNFα. Importantly, NK cells applied to the vascular compartment of the IAC model significantly reduced hyphal length, confirming their antifungal activity. Similarly, MAIT cells in sufficiently high quantities reduced hyphal growth and branching, although this effect depended on the recognition of riboflavin-derived antigens, as shown by the lack of response to the <i>A. fumigatus ΔriboB</i> mutant strain. Together, our findings demonstrate that the advanced IAC model is a powerful tool to dissect human antifungal immunity. The interactions observed between macrophages and other immune cells highlight the importance of multi-layered defense strategies against <i>A. fumigatus</i>.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"7 ","pages":"uqag034"},"PeriodicalIF":0.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076817","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}
microLifePub Date : 2026-09-08eCollection Date: 2026-01-01DOI: 10.1093/femsml/uqag033
Alexandre Hervé, Jean Cury, Aude Bernheim
{"title":"Characterization of syntons across bacterial genomes using non-redundant genomic contexts.","authors":"Alexandre Hervé, Jean Cury, Aude Bernheim","doi":"10.1093/femsml/uqag033","DOIUrl":"10.1093/femsml/uqag033","url":null,"abstract":"<p><p>Bacterial genomes are dynamic, shaped by gene gain, loss, and horizontal transfer; yet selection preserves the colocalization of functionally coupled genes into recurrent modules known as syntons. Many large-scale approaches do not explicitly account for phylogenetic relatedness between genomes which can inflate support for associations that are simply shared by close relatives. To address this, we introduce a scalable framework that clusters gene-family occurrences by genomic neighborhood and counts co-occurrences across distinct genomic contexts, reducing redundancy from vertical inheritance and uneven database sampling without explicit phylogenetic reconstruction. Applied to 32 791 RefSeq genomes comprising 123 million genes, this approach identifies 15 million syntons across 779 000 synton families, characterizing their diversity and revealing structured associations among antiphage defense systems. Leveraging this context-aware framework, we also introduce context residual entropy to quantify gene families neighborhood variability. By prioritizing independent evolutionary events over redundant genome-level counts, our approach provides a scalable, phylogenetic tree-free view of modular organization across bacterial genomes.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"7 ","pages":"uqag033"},"PeriodicalIF":0.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119641","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}
microLifePub Date : 2026-08-25eCollection Date: 2026-01-01DOI: 10.1093/femsml/uqag031
Andrew B Higginson, Jasmine Soh, Stephen R Garrett, Terry K Smith, Tim R Blower, Tracy Palmer
{"title":"A novel reverse lipase toxin substrate of the <i>Staphylococcus aureus</i> type VII secretion system.","authors":"Andrew B Higginson, Jasmine Soh, Stephen R Garrett, Terry K Smith, Tim R Blower, Tracy Palmer","doi":"10.1093/femsml/uqag031","DOIUrl":"10.1093/femsml/uqag031","url":null,"abstract":"<p><p>The type VII secretion system (T7SS) is found in many Gram-positive bacteria and secretes toxins with antibacterial activity. Most characterized substrates have an N-terminal LXG domain that interacts with other helical partner proteins to form a composite T7SS targeting signal. Here we describe only the second substrate family to have a reverse domain arrangement. We show that TslM has a C-terminal LXG-like domain and an N-terminal lipase domain that has phospholipase activity. Secretion of TslM requires a single helical partner protein that binds to the TslM C-terminus, and its toxic activity is neutralized by a distinct family of membrane proteins. Genome analysis reveals that <i>Staphylococcus aureus</i> strains have the capacity to encode up to seven paralogous copies of this toxin family. Taken together our findings show that lipases are an important component of the staphylococcal T7SS toxin arsenal, and that toxins with a reverse domain arrangement are more widespread than previously appreciated.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"7 ","pages":"uqag031"},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946280","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}
microLifePub Date : 2026-08-18eCollection Date: 2026-01-01DOI: 10.1093/femsml/uqag029
Wolfgang R Hess, Kai Papenfort, Cynthia M Sharma, Franz Narberhaus, Ruth A Schmitz
{"title":"Small proteins in prokaryotes, a fascinating world.","authors":"Wolfgang R Hess, Kai Papenfort, Cynthia M Sharma, Franz Narberhaus, Ruth A Schmitz","doi":"10.1093/femsml/uqag029","DOIUrl":"10.1093/femsml/uqag029","url":null,"abstract":"","PeriodicalId":74189,"journal":{"name":"microLife","volume":"7 ","pages":"uqag029"},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857976","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}
microLifePub Date : 2026-08-18eCollection Date: 2026-01-01DOI: 10.1093/femsml/uqag030
Merle Lisa Hammer, Maria Joanna Niemiec, Jonas Baumgarten, Isabel Auge, Friederike Sophie Gorki, Alex Steimle, Julia-Stefanie Frick, Alesia Walker, Ilse Denise Jacobsen
{"title":"<i>Phocaeicola vulgatus</i> mpk colonization protects epithelial cells from <i>Candida albicans</i> infection.","authors":"Merle Lisa Hammer, Maria Joanna Niemiec, Jonas Baumgarten, Isabel Auge, Friederike Sophie Gorki, Alex Steimle, Julia-Stefanie Frick, Alesia Walker, Ilse Denise Jacobsen","doi":"10.1093/femsml/uqag030","DOIUrl":"10.1093/femsml/uqag030","url":null,"abstract":"<p><p><i>Candida albicans</i> is an opportunistic pathogen residing in the gastro-intestinal tract of humans from where it can cause life-threatening systemic infection. Dysbiosis is one predisposing factor for <i>C. albicans</i> overgrowth, indicating that commensal bacteria limit fungal growth and convey colonization resistance. <i>Phocaeicola vulgatus</i> (formerly classified as <i>Bacteroides</i>) is an abundant gut commensal. We show that <i>P. vulgatus</i> can protect enterocytes <i>in vitro</i> from <i>C. albicans</i> damage. The protective effect is most pronounced if the bacteria pre-colonize host cells 6 h prior to addition of <i>C. albicans</i>. Colonization of the enterocytes with <i>P. vulgatus</i> leads to reduced adhesion of <i>C. albicans</i>, shorter hyphae, and increased fungal shedding, while the overall fungal burden is not reduced. The protective effect is contact-dependent but can be elicited to some degree by heat-inactivated bacterial cells. Our findings suggest that multiple mechanisms mediate the protective effect, including activation of self-defenses of the host cells to shed the pathogen, as well as a direct antagonistic interaction between the fungi and the bacteria targeting <i>C. albicans</i> filamentation, and thereby hyphae-associated virulence factors.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"7 ","pages":"uqag030"},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889692","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}
microLifePub Date : 2026-07-20eCollection Date: 2026-01-01DOI: 10.1093/femsml/uqag027
Denise Pytlik, Milan Gerovac, Thorsten Bischler, Andreas Schlosser, Jörg Vogel, Christoph Schoen
{"title":"The CRISPR/Cas-associated scaRNA modulates <i>efeUOB</i> expression and stress responses in <i>Neisseria meningitidis</i>.","authors":"Denise Pytlik, Milan Gerovac, Thorsten Bischler, Andreas Schlosser, Jörg Vogel, Christoph Schoen","doi":"10.1093/femsml/uqag027","DOIUrl":"10.1093/femsml/uqag027","url":null,"abstract":"<p><p><i>Neisseria meningitidis</i> is a human-adapted commensal pathogen that must continuously balance nutrient acquisition with stress tolerance. Here, we identify a type II-C CRISPR/Cas-associated small RNA (scaRNA) as a posttranscriptional regulator of the <i>efeUOB</i> operon and oxidative stress responses. Using <i>in vitro</i> RNA binding and structure probing assays, we show that the scaRNA interacts with the 5' untranslated region of <i>efeO</i> mRNA, leading to reduced translation of this component of the ferrous iron transporter EfeUOB. Consistent with this, <i>efeO</i> translational fusions demonstrate repression by the scaRNA, whereas a ΔscaRNA mutant shows increased reporter expression. We further show that meningococcal Cas9 (Nme1Cas9) is able to cleave scaRNA <i>in vitro</i>, but <i>in vivo</i> phenotypes are primarily scaRNA-dependent, indicating that Nme1Cas9 contributes, at most, indirectly to this regulation. In line with this observation, comparative proteomics revealed overlapping but distinct roles of scaRNA and Nme1Cas9 in oxidative stress adaptation, energy metabolism, and ion transport. While steady-state protein abundances did not capture all scaRNA-dependent effects, functional assays confirmed that scaRNA inactivation reduces survival under oxidative stress. Together, our results identify scaRNA-mediated repression of <i>efeO</i> as a novel posttranscriptional mechanism that contributes to stress adaptation in meningococci. These findings expand the functional repertoire of CRISPR-associated elements and suggest a role for small RNA-based regulation in iron-related stress adaptation in a major human pathogen.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"7 ","pages":"uqag027"},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13431127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671431","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}
microLifePub Date : 2026-07-11eCollection Date: 2026-01-01DOI: 10.1093/femsml/uqag026
Wolfgang R Hess, Anita Marchfelder, Lennart Randau
{"title":"Editorial: creative CRISPR-Cas: RNA-guided functions in defence and beyond.","authors":"Wolfgang R Hess, Anita Marchfelder, Lennart Randau","doi":"10.1093/femsml/uqag026","DOIUrl":"10.1093/femsml/uqag026","url":null,"abstract":"","PeriodicalId":74189,"journal":{"name":"microLife","volume":"7 ","pages":"uqag026"},"PeriodicalIF":0.0,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610857","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}