Irmantas Mogila, Dalia Smalakyte, Gintautas Tamulaitis
{"title":"Expanding arsenal of type III CRISPR-Cas antiviral defense.","authors":"Irmantas Mogila, Dalia Smalakyte, Gintautas Tamulaitis","doi":"10.1093/femsre/fuag057","DOIUrl":"https://doi.org/10.1093/femsre/fuag057","url":null,"abstract":"<p><p>CRISPR-Cas systems are adaptive immune systems that protect prokaryotes from invading genetic elements through acquisition of foreign nucleic acid sequences and RNA-guided recognition of target molecules. Among the diverse CRISPR-Cas families, type III systems represent a highly complex and versatile branch that couples sequence-specific interference with nucleotide-based signaling and activation of diverse downstream immune responses. Recent discoveries have substantially expanded the functional diversity of type III CRISPR-Cas systems, revealing new subtypes, ancillary effectors, nucleotide second messengers, signal-degrading enzymes, and viral counter-defense strategies. Here, we summarize current mechanistic and structural insights into type III CRISPR-Cas biology, from adaptation and target recognition to immune signaling, ancillary effector-mediated responses, and defense regulation. We further discuss emerging biotechnological applications of type III systems and highlight key unanswered questions shaping future research in this rapidly evolving field.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149319519","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":"Prokaryotes bridging the lipid divide.","authors":"Rubén García-Domínguez, Damien P Devos","doi":"10.1093/femsre/fuag056","DOIUrl":"https://doi.org/10.1093/femsre/fuag056","url":null,"abstract":"<p><p>The fundamental biochemical and stereochemical difference in how cell membrane lipids are built between Archaea on one side, and Bacteria and Eukarya on the other is known as the lipid divide. It is often assumed to translate in the impossibility of combining membranes of both types. It was established early when little sampling of the biodiversity was available. Since then, exceptions have been revealed and accumulated. Here, we review those exceptions and complement them with a broad survey, revealing diverse bacteria with mixed membrane-lipid features. Together with liposome assays and synthetic-biology experiments, studies on these organisms suggest that the lipid divide can be bridged. We conclude by discussing the evolutionary implications for LUCA, the origin of the prokaryotic domains and eukaryogenesis.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149319520","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":"The Pathomycosphere: A Spatially Defined Framework in Pathogen Ecology.","authors":"Gayan Abeysinghe, Sanjay Antony-Babu","doi":"10.1093/femsre/fuag054","DOIUrl":"https://doi.org/10.1093/femsre/fuag054","url":null,"abstract":"<p><p>Fungal pathogens have historically been studied as autonomous agents, as self-contained units independent of their associated microbiota, with disease outcomes attributed to fungal virulence factors acting on susceptible hosts. However, many pathogenic fungi harbor bacterial associates that influence their ecology, persistence and virulence. The pathobiome concept addressed this limitation by framing disease as an outcome of multi-kingdom interactions. Yet most pathobiome studies rely on correlative analyses of microbial abundances with pathogens, lacking spatial resolution to identify which microorganisms physically interact with pathogenic structures. Conversely, the hyphosphere provides micrometer-scale spatial resolution but has been investigated predominantly in non-pathogenic fungi. Here, we propose the pathomycosphere as a spatially defined and experimentally tractable subset of the pathobiome: a hypha-associated microbial assemblage in which physical association with the pathogenic member, prolonged or transient has a consequence for the pathogen's biology, with pathogenicity residing in the fungus, an associated microorganism or their interaction. This framework bridges the pathobiome and hyphosphere concepts by anchoring disease-associated microbial interactions to hyphal interface, where mechanistic investigation becomes feasible. Pathomycosphere provides operational tractability to explore microbial partnerships contributing to pathogenesis, and positions fungal-associated bacterial consortia as important components of pathogen biology with relevance to disease ecology beyond agricultural systems.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237426","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}
Denisa Vondrova, Sabrina Laura Mugni, Jan Blumenstein, Clara Kasiztky, Federico Sisti, Julieta Fernández, Jana Kamanova
{"title":"Architecture and regulatory functions of c-di-GMP signaling in classical Bordetella species.","authors":"Denisa Vondrova, Sabrina Laura Mugni, Jan Blumenstein, Clara Kasiztky, Federico Sisti, Julieta Fernández, Jana Kamanova","doi":"10.1093/femsre/fuaf065","DOIUrl":"10.1093/femsre/fuaf065","url":null,"abstract":"<p><p>Cyclic di-GMP (c-di-GMP) is a highly conserved bacterial second messenger that regulates important processes such as motility, biofilm formation and virulence. In this review, we investigate the architecture and regulatory functions of c-di-GMP signaling in classical Bordetella species, including B. bronchiseptica, B. parapertussis and B. pertussis. We examine how the c-di-GMP signaling pathway interacts with the BvgAS two-component system and other signaling pathways to coordinate virulence gene expression and surface-associated behaviors in these respiratory pathogens. In particular, we highlight the functions of characterized diguanylate cyclases (DGCs), phosphodiesterases (PDEs) and dual-domain proteins, focusing on regulatory modules such as the BdcA-DdpA scaffold complex, the oxygen-sensing DGC BpeGReg and the LapD-LapG proteolytic switch that controls BrtA adhesin. We also propose a model for the function of BvgR, a PDE-like protein lacking catalytic residues, and discuss how c-di-GMP suppresses the type III secretion system. Importantly, we highlight the diversity of the c-di-GMP network in classical Bordetella species, likely reflecting their evolutionary specialization. To conclude, we outline important open questions and suggest future research directions, including the identification of sensory ligands and c-di-GMP effectors. Overall, our review illustrates the importance of c-di-GMP as a critical, but still incompletely understood, regulatory hub in Bordetella pathogenesis.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":" ","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12805831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833328","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":"Role of myeloid cells expressing CD169/Siglec-1 in host-pathogen interactions.","authors":"Ilona Ronco, Branka Horvat","doi":"10.1093/femsre/fuag013","DOIUrl":"10.1093/femsre/fuag013","url":null,"abstract":"<p><p>CD169/Siglec-1 is a type-I transmembrane lectin receptor expressed on subcapsular sinus macrophages and activated monocytes, which plays a key role in innate immune surveillance and orchestration of adaptive immunity. As a sialic acid-binding immunoglobulin-like lectin (Siglec), CD169 recognizes sialylated gangliosides and glycoconjugates present on surface of several viral envelopes, including HIV-1, SARS-CoV-2, and Ebola virus as well as sialylated bacterial capsules such as those of Neisseria meningitidis and Campylobacter jejuni. Moreover, different viruses were shown to be captured by CD169+ cells which could play distinctive role during infections: they could enhance efficient immune responses, but also facilitate pathogen dissemination through viral capture and transfer to permissive cells. This last mechanism has been well documented for HIV-1, where CD169 mediates viral trans-infection of CD4⁺ T-cells. CD169 expression is rapidly induced by type-I interferons during acute viral infections and has emerged as a valuable biomarker to distinguish viral from bacterial infection, particularly for COVID-19 and influenza. Detectable by flow cytometry, CD169 represents a solid biomarker in clinical settings and possible target in the development of novel prophylactic and therapeutic strategies. Its dual role, protective in host defence yet exploitable by certain pathogens, highlights the need for careful consideration in future therapeutic approaches.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485233","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}
Mohor Mitra, Sajan, Shrutarshi Paul, Amit Huppert, Edouard Jurkevitch
{"title":"From microbes to animals: a review on prey choice and prey-predator dynamics across organismal scales.","authors":"Mohor Mitra, Sajan, Shrutarshi Paul, Amit Huppert, Edouard Jurkevitch","doi":"10.1093/femsre/fuag004","DOIUrl":"10.1093/femsre/fuag004","url":null,"abstract":"<p><p>Predator-prey interactions are intricately linked to ecological systems, from micro-organisms to large animals. Most predator-prey studies use simplified pairwise interactions, constraining our ability to identify general principles. Here, predator-prey choices are examined across scales and levels of environmental complexity. We review current knowledge and emphasize the diversity and complexity of predator-prey systems, point to challenges in integrating them, and propose a framework that could benefit predictive modeling for ecosystem functioning and resilience. To do so, we compare the tools, mechanisms, and strategies deployed by micro- and macro- predators and prey defenses to show that commonalities become identifiable, and suggest structural and functional links between micro- and macro-scales. This provides arguments for both descriptive, and mathematical models. We propose that the use of microbial predators like the Bdellovibrio and like organisms can greatly advance the integration of experimental and mathematical modeling research, as they can provide robust empirical observations of predator-prey interactions tested under multiple conditions and levels of complexity. This facilitates model development, in turn leading to new hypotheses. We conclude by showing examples of current developments, that predator-prey interaction-based knowledge has the potential to provide novel medical tools and to improve environmental and agricultural management.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164683","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":"Translation quality control in Pseudomonas aeruginosa: current knowledge and perspectives.","authors":"Bastien L'Hermitte, Reynald Gillet, Christine Baysse","doi":"10.1093/femsre/fuag018","DOIUrl":"10.1093/femsre/fuag018","url":null,"abstract":"<p><p>The fitness and virulence of Pseudomonas aeruginosa rely on its ability to maintain a functional pool of ribosomes, which are essential for protein synthesis. This review explores the intricate ways of ribosome protection, rescue, and hibernation, by which P. aeruginosa preserves ribosome functionality under stress. These processes enhance the adaptability and resistance of this pathogen to ribosome-targeting antibiotics and present significant challenges to current therapeutic strategies. By highlighting recent discoveries and identifying promising directions for future research, this review aims to explore potential targets for innovative drug discovery.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688846","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}
Charlotte Sprason, Philip Donkersley, Jason P Chin, Alexandre Benedetto
{"title":"Caenorhabditis elegans as an experimental model for resilience-boosting microbiota interventions in nonmodel ectotherms.","authors":"Charlotte Sprason, Philip Donkersley, Jason P Chin, Alexandre Benedetto","doi":"10.1093/femsre/fuag031","DOIUrl":"10.1093/femsre/fuag031","url":null,"abstract":"<p><p>Ectotherms make up most animal species and deliver essential services to ecosystems and human food supply chains but are highly vulnerable to environmental perturbations. Being vastly underrepresented in laboratory-based studies, we also critically lack knowledge and approaches to improve their resilience to emerging threats from climate change and anthropogenic activities. With the gut microbiota critically modulating animal health, including stress tolerance, gut microbial interventions may offer opportunities to improve nonmodel ectotherm resilience to such pressures. Developing such interventions requires knowledge of host-gut microbiota-environment interactions that is critically lacking for most species and needs establishing. The roundworm Caenorhabditis elegans is emerging as a powerful ectotherm model to study host-gut microbiota interactions. Extensively utilized across research fields, C. elegans offers a breadth of resources and methodologies, including bioengineering technologies, defined microbiotas, and host and microbial isolate collections. In this review, we recapitulate C. elegans uses in gut microbiota studies, highlighting strengths and limitations and how it may accelerate mechanistic study of nonmodel ectotherm microbiotas. We notably propose a C. elegans-based strategy to identify, isolate, and study isolates from nonmodel ectotherm species to design microbial interventions that may promote climate resilience in nonmodel species.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419766","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}
Ece Aslan, Ksenia I Lubova, Alex Speer, Wilbert Bitter
{"title":"Getting a grip on StAR-related lipid-transfer (START) domain proteins in bacteria.","authors":"Ece Aslan, Ksenia I Lubova, Alex Speer, Wilbert Bitter","doi":"10.1093/femsre/fuag042","DOIUrl":"10.1093/femsre/fuag042","url":null,"abstract":"<p><p>StAR-related lipid transfer (START) domain proteins comprise a conserved superfamily defined by a characteristic helix-grip fold that enables the binding of hydrophobic ligands. In mammals, START domain proteins have been extensively characterized as key mediators of nonvesicular lipid transport and lipid-dependent signalling pathways. In contrast, the prevalence, structural diversity, and functional roles of START domain proteins in bacteria remain underexplored and for those that are characterized, experimental findings are occasionally conflicting. While bacterial START domains preserve the core helix-grip fold for lipid binding, they are typically smaller and exhibit more limited conformational flexibility than their eukaryotic counterparts. Despite these apparent constraints, available experimental data suggest that bacterial START domains participate in a remarkably broad range of biological processes-including small-molecule binding, metabolic regulation, enzymatic catalysis, and stress adaptation-rather than traditional lipid transport. Bacteria within the phylum Actinomycetota, in particular, have evolved a prolific repertoire of START-domain proteins. As an example, we will discuss the START domain proteins of Mycobacterium tuberculosis in detail, one of which has emerged as a promising drug target. Collectively, this synthesis underscores the functional versatility of the START domain across the domains of life and identifies critical knowledge gaps that warrant further investigation.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790177","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":"Phage cocktails: state-of-the-art technologies and strategies for effective design.","authors":"Tomoyoshi Kaneko, Kanata Nakatsuka, Satoshi Tsuneda","doi":"10.1093/femsre/fuaf061","DOIUrl":"10.1093/femsre/fuaf061","url":null,"abstract":"<p><p>With the growing severity of antimicrobial resistance (AMR), phage therapy has garnered attention as a novel therapeutic alternative. In particular, phage cocktails, which combine multiple phages, potentially offer broader antimicrobial spectra than single-phage applications and may suppress the emergence of resistant bacteria. This comprehensive review systematically examines cutting-edge technologies and effective strategies for designing phage cocktails. Special attention was given to the combination of phages recognizing different receptors, designs based on phage-bacteria infection network analysis, and synergistic effects with antibiotics. Additionally, the analysis of large-scale clinical studies has identified challenges in practical implementation, including ensuring cocktail stability and addressing immune responses. These insights are expected to contribute to the design of more effective phage cocktails and the establishment of novel therapeutic strategies to address AMR.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12776354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700068","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}