Pub Date : 2026-01-14DOI: 10.1016/j.mib.2025.102703
Zoë Reynolds, Sumiti Vinayak
The intestinal protozoan parasite, Cryptosporidium, is a leading cause of diarrhea-associated illness and death in young children, immunocompromised individuals, and neonatal ruminant animals. This apicomplexan parasite completes its entire lifecycle within a single host, involving a timely and coordinated progression through asexual and sexual developmental stages. With no fully effective drugs or vaccines available, a deeper understanding of the parasite’s lifecycle stages is crucial for identifying new molecular targets for disease intervention. In this review, we discuss recent advances in understanding the Cryptosporidium developmental lifecycle, stage-specific gene expression, and the role of parasite proteins in invasion, asexual proliferation, and sexual stages. We also discuss the lifecycle stages targeted by a few highly effective anticryptosporidial compounds.
{"title":"Insights into the lifecycle of Cryptosporidium and compounds targeting developmental stages","authors":"Zoë Reynolds, Sumiti Vinayak","doi":"10.1016/j.mib.2025.102703","DOIUrl":"10.1016/j.mib.2025.102703","url":null,"abstract":"<div><div>The intestinal protozoan parasite, <em>Cryptosporidium</em>, is a leading cause of diarrhea-associated illness and death in young children, immunocompromised individuals, and neonatal ruminant animals. This apicomplexan parasite completes its entire lifecycle within a single host, involving a timely and coordinated progression through asexual and sexual developmental stages. With no fully effective drugs or vaccines available, a deeper understanding of the parasite’s lifecycle stages is crucial for identifying new molecular targets for disease intervention. In this review, we discuss recent advances in understanding the <em>Cryptosporidium</em> developmental lifecycle, stage-specific gene expression, and the role of parasite proteins in invasion, asexual proliferation, and sexual stages. We also discuss the lifecycle stages targeted by a few highly effective anticryptosporidial compounds.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"89 ","pages":"Article 102703"},"PeriodicalIF":7.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973202","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}
Pub Date : 2026-01-09DOI: 10.1016/j.mib.2025.102702
Hellen Huang , Mary J Dunlop
Single-cell resolution studies have transformed our understanding of microbial systems, revealing substantial cell-to-cell heterogeneity and complex dynamic behaviors. This review describes recent advances in using optogenetics, where light-sensitive proteins control cellular processes, to investigate microbial behavior at the individual cell level. We discuss studies where optogenetic approaches have enabled high-resolution analysis of properties such as relative cell positioning, subcellular localization, morphology, and gene expression dynamics. In addition, we highlight emerging feedback and event-driven control methods that dynamically modulate cellular states using light signals. By leveraging light's unique capabilities for spatial and temporal manipulation, researchers can now probe cellular characteristics with unprecedented precision. We anticipate significant advances as researchers introduce more sophisticated dynamically patterned light signals for single-cell microbial research.
{"title":"Single-cell analysis and control of microbial systems using optogenetics","authors":"Hellen Huang , Mary J Dunlop","doi":"10.1016/j.mib.2025.102702","DOIUrl":"10.1016/j.mib.2025.102702","url":null,"abstract":"<div><div>Single-cell resolution studies have transformed our understanding of microbial systems, revealing substantial cell-to-cell heterogeneity and complex dynamic behaviors. This review describes recent advances in using optogenetics, where light-sensitive proteins control cellular processes, to investigate microbial behavior at the individual cell level. We discuss studies where optogenetic approaches have enabled high-resolution analysis of properties such as relative cell positioning, subcellular localization, morphology, and gene expression dynamics. In addition, we highlight emerging feedback and event-driven control methods that dynamically modulate cellular states using light signals. By leveraging light's unique capabilities for spatial and temporal manipulation, researchers can now probe cellular characteristics with unprecedented precision. We anticipate significant advances as researchers introduce more sophisticated dynamically patterned light signals for single-cell microbial research.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"89 ","pages":"Article 102702"},"PeriodicalIF":7.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920860","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}
Pub Date : 2026-01-05DOI: 10.1016/j.mib.2025.102700
Crislaine KS Rocha, Ángeles Hueso-Gil, Lorea Alejaldre, Juan Rico, Paula Múgica-Galán, Ángel Goñi-Moreno
Microbes process input information into output responses through diverse genetic and metabolic mechanisms, effectively making them physical systems that compute. These computations profoundly shape the environment, from driving key chemical cycles in the soil to influencing the planet’s atmosphere. Yet the complexity of natural microbial computations remains poorly understood, including the symbolic representation of information and the underlying algorithmic principles. Synthetic biology provides tools to implement simple but effective genetic circuits in living cells, enabling human-defined computations. These are typically Boolean gates and circuits for combinatorial input processing, but they also include sequential logic, memory-based systems, analog circuits, and distributed computations in cellular consortia. Twenty-five years after the first synthetic genetic circuits were built, the field is now exploring new approaches to move closer to the computing power of natural microbes. With a focus on bacteria, this review examines both natural and synthetic functions with the aim of bridging the complexity gap between them and argues that understanding and formalizing the ways in which microbes compute may be essential for improving synthetic genetic circuitry.
{"title":"Exploring the computing power of microbes that shapes the environment","authors":"Crislaine KS Rocha, Ángeles Hueso-Gil, Lorea Alejaldre, Juan Rico, Paula Múgica-Galán, Ángel Goñi-Moreno","doi":"10.1016/j.mib.2025.102700","DOIUrl":"10.1016/j.mib.2025.102700","url":null,"abstract":"<div><div>Microbes process input information into output responses through diverse genetic and metabolic mechanisms, effectively making them physical systems that compute. These computations profoundly shape the environment, from driving key chemical cycles in the soil to influencing the planet’s atmosphere. Yet the complexity of natural microbial computations remains poorly understood, including the symbolic representation of information and the underlying algorithmic principles. Synthetic biology provides tools to implement simple but effective genetic circuits in living cells, enabling human-defined computations. These are typically Boolean gates and circuits for combinatorial input processing, but they also include sequential logic, memory-based systems, analog circuits, and distributed computations in cellular consortia. Twenty-five years after the first synthetic genetic circuits were built, the field is now exploring new approaches to move closer to the computing power of natural microbes. With a focus on bacteria, this review examines both natural and synthetic functions with the aim of bridging the complexity gap between them and argues that understanding and formalizing the ways in which microbes compute may be essential for improving synthetic genetic circuitry.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"89 ","pages":"Article 102700"},"PeriodicalIF":7.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910941","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}
Pub Date : 2026-01-03DOI: 10.1016/j.mib.2025.102701
Robert C Brewster, Vinuselvi Parisutham
Designing regulatable promoters with specified functional output remains difficult because natural promoters are unlikely to match a particular specification, and the sequence design space is large, complex, and challenging to interpret. This review advances a context-minimized, measurement-first approach in Escherichia coli that couples simple assays to a single transcription factor (TF)-based thermodynamic framework. The model is structured around two key concepts related to the TF: occupancy and function. Here, we outline how these concepts can be manipulated and measured at the level of DNA sequence and how those perturbations can impact fold-change and thus features of the promoter, such as dynamic range, leakiness, and sensitivity. LacI serves as a worked example in which sequence–occupancy, copy number, and competition, position-dependent function, and inducer allostery have been measured and can be combined to optimize response features. Overall, simple measurements linked to interpretable models provide a practical route to compiling desired regulatory specifications into sequence-level designs.
{"title":"Model-guided design of regulatable promoters for synthetic biology","authors":"Robert C Brewster, Vinuselvi Parisutham","doi":"10.1016/j.mib.2025.102701","DOIUrl":"10.1016/j.mib.2025.102701","url":null,"abstract":"<div><div>Designing regulatable promoters with specified functional output remains difficult because natural promoters are unlikely to match a particular specification, and the sequence design space is large, complex, and challenging to interpret. This review advances a context-minimized, measurement-first approach in <em>Escherichia coli</em> that couples simple assays to a single transcription factor (TF)-based thermodynamic framework. The model is structured around two key concepts related to the TF: occupancy and function. Here, we outline how these concepts can be manipulated and measured at the level of DNA sequence and how those perturbations can impact fold-change and thus features of the promoter, such as dynamic range, leakiness, and sensitivity. LacI serves as a worked example in which sequence–occupancy, copy number, and competition, position-dependent function, and inducer allostery have been measured and can be combined to optimize response features. Overall, simple measurements linked to interpretable models provide a practical route to compiling desired regulatory specifications into sequence-level designs.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"89 ","pages":"Article 102701"},"PeriodicalIF":7.5,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898808","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}
Pub Date : 2025-12-29DOI: 10.1016/j.mib.2025.102699
Zackary J Jay , Matthew Kellom , Emiley Eloe-Fadrosh , Roland Hatzenpichler
The recent demonstration that members of at least three classes of archaea affiliated with the Thermoproteota superphylum are involved in the production of the climate-active gas methane has sparked discussions about how well we understand the diversity of methanogens. Here, we show that members of all three of these lineages, as well as several other, yet uncultured and physiologically uncharacterized groups within the Thermoproteota that encode the key enzyme of anaerobic methane cycling, methyl-coenzyme M reductase (MCR), are widely distributed in anoxic ecosystems. We postulate that the taxonomic, metabolic, and ecological diversity of methanogenic and MCR-encoding Thermoproteota are poorly understood, and that the contribution of methylotrophic and thermoproteotal methanogenesis to methane production is largely unknown. We hypothesize that thermoproteotal methanogens could contribute, potentially substantially, to methane emissions in many anoxic environments that harbor methylated precursors, including wetlands, sediments, peat, rice paddies, wastewater sludge, and geothermal systems. We highlight the necessity to experimentally test the (eco)physiology of these widely distributed archaea using both culture-dependent (in vitro) and culture-independent (in situ) approaches to assess their potential contribution to methane emissions. Last, we stress the importance of remaining agnostic about the physiology of MCR-encoding Thermoproteota in the absence of experimental data because most of these archaea also carry the genetic potential to grow non-methanogenically.
{"title":"Ecology of methyl-coenzyme M reductase encoding Thermoproteota","authors":"Zackary J Jay , Matthew Kellom , Emiley Eloe-Fadrosh , Roland Hatzenpichler","doi":"10.1016/j.mib.2025.102699","DOIUrl":"10.1016/j.mib.2025.102699","url":null,"abstract":"<div><div>The recent demonstration that members of at least three classes of archaea affiliated with the Thermoproteota superphylum are involved in the production of the climate-active gas methane has sparked discussions about how well we understand the diversity of methanogens. Here, we show that members of all three of these lineages, as well as several other, yet uncultured and physiologically uncharacterized groups within the Thermoproteota that encode the key enzyme of anaerobic methane cycling, methyl-coenzyme M reductase (MCR), are widely distributed in anoxic ecosystems. We postulate that the taxonomic, metabolic, and ecological diversity of methanogenic and MCR-encoding Thermoproteota are poorly understood, and that the contribution of methylotrophic and thermoproteotal methanogenesis to methane production is largely unknown. We hypothesize that thermoproteotal methanogens could contribute, potentially substantially, to methane emissions in many anoxic environments that harbor methylated precursors, including wetlands, sediments, peat, rice paddies, wastewater sludge, and geothermal systems. We highlight the necessity to experimentally test the (eco)physiology of these widely distributed archaea using both culture-dependent (<em>in vitro</em>) and culture-independent (<em>in situ</em>) approaches to assess their potential contribution to methane emissions. Last, we stress the importance of remaining agnostic about the physiology of MCR-encoding Thermoproteota in the absence of experimental data because most of these archaea also carry the genetic potential to grow non-methanogenically.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"89 ","pages":"Article 102699"},"PeriodicalIF":7.5,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862207","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}
Pub Date : 2025-12-22DOI: 10.1016/j.mib.2025.102695
Shanna Bonanno , Neel S Joshi
The human gastrointestinal tract hosts a dense microbial community that closely interfaces with the mucosal immune system to preserve homeostasis. While dysregulation of this interaction contributes to certain disease states, through targeted microbial engineering, these interactions can be modulated for therapeutic benefit. Although engineered microbial therapeutics have shown encouraging preclinical results, few approaches have progressed into clinical pipelines. This gap highlights the need for engineered microbes with greater precision, reliability, and context-dependent control. The innate immune system is primed to rapidly sense microbial signals through pattern recognition receptors and provides accessible and tractable targets for such interventions. This review highlights four strategies that have used engineered probiotics to modulate innate immunity: (1) direct immune cell engagement through surface-display, (2) production of soluble immune effectors, (3) extracellular vesicles for delivery of immune modulators, and (4) environmentally responsive systems to enable spatial and temporal control over immune modulation. Bridging microbial engineering with mucosal immunology can enable engineered probiotics to function as dynamic, context-aware immunomodulators.
{"title":"Engineering microbes to modulate innate immune signaling: strategies for host–microbe interactions","authors":"Shanna Bonanno , Neel S Joshi","doi":"10.1016/j.mib.2025.102695","DOIUrl":"10.1016/j.mib.2025.102695","url":null,"abstract":"<div><div>The human gastrointestinal tract hosts a dense microbial community that closely interfaces with the mucosal immune system to preserve homeostasis. While dysregulation of this interaction contributes to certain disease states, through targeted microbial engineering, these interactions can be modulated for therapeutic benefit. Although engineered microbial therapeutics have shown encouraging preclinical results, few approaches have progressed into clinical pipelines. This gap highlights the need for engineered microbes with greater precision, reliability, and context-dependent control. The innate immune system is primed to rapidly sense microbial signals through pattern recognition receptors and provides accessible and tractable targets for such interventions. This review highlights four strategies that have used engineered probiotics to modulate innate immunity: (1) direct immune cell engagement through surface-display, (2) production of soluble immune effectors, (3) extracellular vesicles for delivery of immune modulators, and (4) environmentally responsive systems to enable spatial and temporal control over immune modulation. Bridging microbial engineering with mucosal immunology can enable engineered probiotics to function as dynamic, context-aware immunomodulators.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"89 ","pages":"Article 102695"},"PeriodicalIF":7.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818490","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}
Pub Date : 2025-12-19DOI: 10.1016/j.mib.2025.102698
Vorrapon Chaikeeratisak , Poochit Nonejuie , Chase J Morgan
The increasing emergence of multidrug-resistant bacterial infections poses a major threat to humankind, with 10 million deaths predicted in 2050 as a result. Phage therapy has therefore regained attention as a promising approach to combat these pathogens. However, the ongoing evolutionary arms race between phages and bacteria has driven the accumulation of phage defense systems in bacterial populations, which can compromise the efficacy and generalizability of phage applications. Recently, nucleus-forming phages have been discovered and classified under the newly established phage family ‘Chimalliviridae’. Chimalliviruses orchestrate a highly organized, nucleus-based replication that physically segregates phage DNA from host defenses, thereby enhancing replication efficiency and conferring resistance to a wide array of host defenses. Their unique replication strategy and subcellular organization far exceed that of classical phages, positioning them as candidates for a new class of ‘next-generation phages’ with superior therapeutic potential and biocontrol capabilities. This review will cover the current landscape of chimallivirus discovery, highlighting their association with bacterial pathogens, unique replication machinery, and interaction with bacterial defenses. Furthermore, it provides insights into chimallivirus-based therapeutic applications.
{"title":"Nucleus-forming phages: from subcellular organization and viral–host interplay to prospects for phage applications","authors":"Vorrapon Chaikeeratisak , Poochit Nonejuie , Chase J Morgan","doi":"10.1016/j.mib.2025.102698","DOIUrl":"10.1016/j.mib.2025.102698","url":null,"abstract":"<div><div>The increasing emergence of multidrug-resistant bacterial infections poses a major threat to humankind, with 10 million deaths predicted in 2050 as a result. Phage therapy has therefore regained attention as a promising approach to combat these pathogens. However, the ongoing evolutionary arms race between phages and bacteria has driven the accumulation of phage defense systems in bacterial populations, which can compromise the efficacy and generalizability of phage applications. Recently, nucleus-forming phages have been discovered and classified under the newly established phage family ‘Chimalliviridae’. Chimalliviruses orchestrate a highly organized, nucleus-based replication that physically segregates phage DNA from host defenses, thereby enhancing replication efficiency and conferring resistance to a wide array of host defenses. Their unique replication strategy and subcellular organization far exceed that of classical phages, positioning them as candidates for a new class of ‘next-generation phages’ with superior therapeutic potential and biocontrol capabilities. This review will cover the current landscape of chimallivirus discovery, highlighting their association with bacterial pathogens, unique replication machinery, and interaction with bacterial defenses. Furthermore, it provides insights into chimallivirus-based therapeutic applications.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"89 ","pages":"Article 102698"},"PeriodicalIF":7.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797402","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}
Pub Date : 2025-12-19DOI: 10.1016/j.mib.2025.102697
Tom J Arrowsmith , Maria Puiu , Tim R Blower
Shutoff of host translation is a common immunity strategy employed by bacteria to defend against predatory bacteriophages. Many bacterial toxin–antitoxin systems specifically target and inactivate tRNAs to achieve translational inhibition, potentially in response to phage infection. Common modes of action include modification, cleavage or re-allocation of target tRNAs. Recent studies have also identified key determinants of specificity for tRNA-targeting toxins. Herein, we discuss toxin action and specificity in the context of phage defence. As a counterpoint, we consider virally encoded tRNAs as counter-defences and drivers of phage evolution.
{"title":"tRNAs as toxin targets in phage defence and a focus of counter-defence against abortive infection","authors":"Tom J Arrowsmith , Maria Puiu , Tim R Blower","doi":"10.1016/j.mib.2025.102697","DOIUrl":"10.1016/j.mib.2025.102697","url":null,"abstract":"<div><div>Shutoff of host translation is a common immunity strategy employed by bacteria to defend against predatory bacteriophages. Many bacterial toxin–antitoxin systems specifically target and inactivate tRNAs to achieve translational inhibition, potentially in response to phage infection. Common modes of action include modification, cleavage or re-allocation of target tRNAs. Recent studies have also identified key determinants of specificity for tRNA-targeting toxins. Herein, we discuss toxin action and specificity in the context of phage defence. As a counterpoint, we consider virally encoded tRNAs as counter-defences and drivers of phage evolution.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"89 ","pages":"Article 102697"},"PeriodicalIF":7.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797403","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}
Pub Date : 2025-12-17DOI: 10.1016/j.mib.2025.102696
Natasha Torriero-Smith , Benjamin A Rogers , Michael J McDonald , Jeremy J Barr
Bacteriophages (phages) are viruses that selectively prey on bacteria. Their use in treating antimicrobial-resistant bacterial infections is steadily increasing due to the need for alternative therapies. The application of phage therapy is not without its challenges, including difficulties associated with isolating phages against a target strain, the limited infectivity of a phage, the cost and complexity of producing well-characterised phage stocks, and the emergence of phage resistance. The directed adaptation of phage to a specific bacterial target, also known as ‘phage training’, leverages the natural evolutionary capacity of phages and can be used to bolster their bacterial killing abilities. Phage training dates back almost as far as phage therapy itself, being used to expand the therapeutic use of phages. Numerous reports showcase the success and benefits of phage training in vitro and its potential to operate effectively within the framework of phage therapy. However, the time needed to train a given phage, followed by genotypic and phenotypic characterisation of both pre- and post-trained phages, is a major limitation. Here, we explore oversights of the phage training process and propose some considerations and solutions to help drive the field forward to enable its feasible integration into phage therapy.
{"title":"Harnessing ‘phage training’ to bolster the therapeutic potential of bacteriophages","authors":"Natasha Torriero-Smith , Benjamin A Rogers , Michael J McDonald , Jeremy J Barr","doi":"10.1016/j.mib.2025.102696","DOIUrl":"10.1016/j.mib.2025.102696","url":null,"abstract":"<div><div>Bacteriophages (phages) are viruses that selectively prey on bacteria. Their use in treating antimicrobial-resistant bacterial infections is steadily increasing due to the need for alternative therapies. The application of phage therapy is not without its challenges, including difficulties associated with isolating phages against a target strain, the limited infectivity of a phage, the cost and complexity of producing well-characterised phage stocks, and the emergence of phage resistance. The directed adaptation of phage to a specific bacterial target, also known as ‘phage training’, leverages the natural evolutionary capacity of phages and can be used to bolster their bacterial killing abilities. Phage training dates back almost as far as phage therapy itself, being used to expand the therapeutic use of phages. Numerous reports showcase the success and benefits of phage training <em>in vitro</em> and its potential to operate effectively within the framework of phage therapy. However, the time needed to train a given phage, followed by genotypic and phenotypic characterisation of both pre- and post-trained phages, is a major limitation. Here, we explore oversights of the phage training process and propose some considerations and solutions to help drive the field forward to enable its feasible integration into phage therapy.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"89 ","pages":"Article 102696"},"PeriodicalIF":7.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780622","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}
Pub Date : 2025-12-13DOI: 10.1016/j.mib.2025.102685
Avery M Brewer , Dalton R George , Emma K Frow
In this review, we identify emerging trends in the governance and policy landscape surrounding the real-world deployment of genetically engineered microbes (GEMs), focusing on the United States and Europe. A recent wave of commercialized GEMs in the US suggests that interest in developing GEMs for open release might be on the rise, after a 40-year period of very low commercial activity. GEMs are receiving renewed attention for their potential roles in agriculture, sustainable manufacturing, biosensing, environmental restoration, energy production, and human health. Advances in genetic modification technologies, combined with the growing number of possible open release applications for GEMs, stand to challenge existing governance frameworks in several ways. First, the feasibility of either strict product- or process-based regulatory frameworks for biotechnology is being increasingly tested. Second, the desirability of long-term persistence and ecological action of GEMs in some application contexts complicates the logic of typical risk assessments for deliberate release of genetically modified organisms. Synergistic, long-term, and indirect impacts of open release are challenging to reliably predict and call for risk assessment methods able to accommodate high levels of uncertainty or ignorance. Third, increasing variety in application types for GEMs is likely to yield new business models and routes to market. Approaches such as direct-to-consumer marketing raise challenging questions around stewardship, consent, transborder movement, and monitoring of GEMs. This constellation of issues will benefit from interdisciplinary research and stakeholder deliberation at local, national, and international levels to promote robust and adaptable GEM governance in the coming decades.
{"title":"Emerging governance considerations for the deployment of genetically engineered microbes","authors":"Avery M Brewer , Dalton R George , Emma K Frow","doi":"10.1016/j.mib.2025.102685","DOIUrl":"10.1016/j.mib.2025.102685","url":null,"abstract":"<div><div>In this review, we identify emerging trends in the governance and policy landscape surrounding the real-world deployment of genetically engineered microbes (GEMs), focusing on the United States and Europe. A recent wave of commercialized GEMs in the US suggests that interest in developing GEMs for open release might be on the rise, after a 40-year period of very low commercial activity. GEMs are receiving renewed attention for their potential roles in agriculture, sustainable manufacturing, biosensing, environmental restoration, energy production, and human health. Advances in genetic modification technologies, combined with the growing number of possible open release applications for GEMs, stand to challenge existing governance frameworks in several ways. First, the feasibility of either strict product- or process-based regulatory frameworks for biotechnology is being increasingly tested. Second, the desirability of long-term persistence and ecological action of GEMs in some application contexts complicates the logic of typical risk assessments for deliberate release of genetically modified organisms. Synergistic, long-term, and indirect impacts of open release are challenging to reliably predict and call for risk assessment methods able to accommodate high levels of uncertainty or ignorance. Third, increasing variety in application types for GEMs is likely to yield new business models and routes to market. Approaches such as direct-to-consumer marketing raise challenging questions around stewardship, consent, transborder movement, and monitoring of GEMs. This constellation of issues will benefit from interdisciplinary research and stakeholder deliberation at local, national, and international levels to promote robust and adaptable GEM governance in the coming decades.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"89 ","pages":"Article 102685"},"PeriodicalIF":7.5,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733933","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}
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