mBio最新文献

{"title":"Resolution of viral R-loop by DHX9 promotes hepatitis B virus replication.","authors":"Yubo Pi, Huimin Luo, Kai Wang, Ni Tang, Ailong Huang, Yanmeng Chen","doi":"10.1128/mbio.01449-26","DOIUrl":"10.1128/mbio.01449-26","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) is a hepatotropic DNA virus with a compact 3.2 kb genome that replicates via reverse transcription. HBV covalently closed circular DNA (cccDNA) transcription shares molecular features with R-loop. DExH-box helicase 9 (DHX9) has been shown to be associated with R-loop accumulation, genome instability, and HBV replication. However, the role of DHX9-mediated R-loop homeostasis in HBV transcription has not yet been elucidated. In this study, we identified a critical role of DHX9 in resolving R-loops at transcription termination during HBV transcription. We demonstrate that HBV replication promotes viral R-loop accumulation. DHX9 promotes HBV R-loop resolution, HBV cccDNA transcription termination, and subsequent nuclear export of the 3.5 kb HBV RNA, facilitating HBV DNA replication. These findings reveal DHX9-mediated R-loop resolution as a potential therapeutic target for antiviral intervention.IMPORTANCEThe persistence of HBV cccDNA poses a major challenge to achieving a cure for chronic hepatitis B. While R-loop structures have been implicated in the life cycles of viruses, their formation and functional significance in HBV replication have remained largely unexplored. This study provides the first evidence that the cellular helicase DHX9 resolves transcription-replication conflicts by dissolving R-loops formed during HBV replication. Our findings also identify DHX9-mediated R-loop resolution as a critical mechanism supporting the HBV life cycle. Consequently, targeting DHX9 presents a promising therapeutic strategy to silence the persistent HBV cccDNA reservoir.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0144926"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular adaptations of fission yeast to inositol starvation.","authors":"Ana M Sanchez, Jill Babor, Michelle Saoi, Isabel Prucker, Henning J Jessen, Beate Schwer, Stewart Shuman","doi":"10.1128/mbio.01864-26","DOIUrl":"10.1128/mbio.01864-26","url":null,"abstract":"<p><p>Inositol is an essential nutrient and a precursor of phosphorylated metabolites that play important roles in cell physiology. Here we characterize the impact of intracellular inositol deficiency, taking advantage of fission yeast <i>Schizosaccharomyces pombe</i>, an obligate inositol auxotroph, as a model system. We find that cells deprived of inositol ceased growth after two or three rounds of division, with genome content indicative of a G2 arrest. Inositol starvation elicited (i) widespread changes in the expression of genes involved in lipid metabolism and inositol polyphosphate dynamics, associated with an across-the-board elevation of triacylglycerol lipids; (ii) depletion of glycerophosphoinositol and accumulation of glycerophosphocholine and choline; (iii) selective depletion of inositol pyrophosphate 1,5-IP₈, and depletion of polyphosphate; (iv) upregulation of autophagy genes; (v) downregulation of genes for the biogenesis and function of ribosomes and tRNAs, accompanied by conversion of polysomes to 80S monosomes; and (vi) large-magnitude changes in mRNAs encoding transcription factors. Our study underscores distinctive and shared features of the cellular responses to inositol deficiency versus phosphate deficiency that enhance our understanding of nutrient stress.</p><p><strong>Importance: </strong>Inositol is an essential precursor of diverse phosphorylated derivatives that govern cell signaling, glucose and lipid metabolism, and cellular phosphate homeostasis. To probe how cells adapt to inositol deprivation, we exploited the fission yeast <i>Schizosaccharomyces pombe</i>, which is unable to synthesize inositol and requires exogenous inositol for growth. Via genome-wide analysis of changes in mRNA levels and tracking the status of inositol-adjacent metabolites, we highlight adaptive responses specific to inositol starvation that affect lipid metabolism and inositol pyrophosphate signaling. Clues to the origins of the transcriptome remodeling during inositol starvation emerged from the large-magnitude increases in mRNAs encoding certain RNA polymerase II transcription factors, which correlated with increased expression of their putative client genes.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0186426"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell analysis of StkP activity reveals the temporal dynamics of DivIVA phosphorylation in <i>Streptococcus pneumoniae</i>.","authors":"Sylvie Manuse, Léo Claude, Pedro M Alzari, Anne Marie Wehenkel, Christophe Grangeasse","doi":"10.1128/mbio.01648-26","DOIUrl":"10.1128/mbio.01648-26","url":null,"abstract":"<p><p>Serine/threonine phosphorylation has emerged as a central regulatory mechanism of the bacterial cell cycle. However, the dynamics and temporal selectivity of protein phosphorylation through the cell cycle remain unamenable to existing analytical tools. Although fluorescent phosphorylation biosensors are widely available in single eukaryotic cells, such tools have yet to be adapted for bacteria. To address this gap, we developed an <i>in vivo</i> fluorescent biosensor specifically designed to monitor serine/threonine phosphorylation in single bacterial cells. Specifically, this sensor reports protein phosphorylation mediated by the serine/threonine kinase StkP, the main regulator of cell division in <i>Streptococcus pneumoniae</i>. We showed that StkP activity is constitutive throughout the cell cycle. However, we observed that StkP-mediated protein phosphorylation is heterogeneous from cell to cell in early stages of the cell cycle. Importantly, our results revealed that the cell division protein DivIVA is found phosphorylated at the cell poles, suggesting an additional regulatory layer controlling its function at this location. Collectively, this work provides original insights into the temporal dynamics of StkP activity and the regulation of the pneumococcal cell cycle by phosphorylation.IMPORTANCEHow bacterial serine/threonine phosphorylation is dynamically regulated in living single cells remains inaccessible, largely because efficient reporters required to monitor phosphorylation <i>in vivo</i> are lacking. In this study, we designed a fluorescent biosensor approach that enables direct visualization of serine/threonine phosphorylation dynamics in single bacterial cells. Using this approach, we revealed that the activity of StkP, the serine/threonine kinase that regulates cell division in <i>Streptococcus pneumoniae</i>, is constitutive throughout the cell cycle, yet StkP-mediated protein phosphorylation is unexpectedly heterogeneous across individual cells in the early stages of division. Importantly, our reporter also showed that the phosphorylation of the key cell division protein DivIVA is highly dynamic. Together, these findings provide the conceptual basis to improve our understanding of the role of phosphorylation in pneumococcal cell division and pave the way for investigating phosphorylation dynamics in other bacterial species.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0164826"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Story behind the Science: Solving the riddle for the pathogenesis of vulvovaginal candidiasis.","authors":"Paul L Fidel, Junko Yano","doi":"10.1128/mbio.01787-26","DOIUrl":"10.1128/mbio.01787-26","url":null,"abstract":"<p><p>For nearly three decades, the pathogenesis of vulvovaginal candidiasis (VVC) remained an enigma. During the HIV/AIDS epidemic, observations that women with profound CD4⁺ T-cell deficiencies were not more susceptible to VVC challenged the prevailing assumption that protective adaptive immunity dictated all mucosal <i>Candida</i> infections. Here, we recount the scientific journey and trajectory that began with these observations and culminated in a paradigm shift in understanding VVC pathogenesis. Through extensive clinical studies, animal models, and a groundbreaking live <i>Candida</i> challenge clinical study, VVC was ultimately redefined as an immunopathogenic condition characterized by a robust yet dysfunctional neutrophil response to <i>C. albicans</i> within the vaginal environment. We highlight the key discoveries, challenges, and experiences that reshaped the field and finally solved the long-standing riddle of VVC pathogenesis.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0178726"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RNA-binding protein Psc1 functions downstream of the NDR/LATS kinase Cbk1 to modulate CO₂ tolerance in <i>Cryptococcus neoformans</i>.","authors":"Emma E Blackburn, Laura C Ristow, Xiaofeng Xie, Damian J Krysan, Xiaorong Lin","doi":"10.1128/mbio.02051-26","DOIUrl":"10.1128/mbio.02051-26","url":null,"abstract":"<p><p><i>Cryptococcus neoformans</i> is an opportunistic fungal pathogen responsible for approximately 20% of deaths in patients with HIV/AIDS. Adaptation to host physiological conditions, including high CO₂, is required for infection. We discovered that an uncharacterized protein with an RNA-binding domain, Psc1, functions as a basidiomycete-specific suppressor of the kinase mutant <i>cbk1</i>Δ and partially rescues its growth defect in high CO₂. Psc1 contains multiple consensus <u>c</u>ell wall <u>b</u>iosynthesis <u>k</u>inase 1 (Cbk1) phosphorylation sites that are required for maintenance of CO₂ fitness. We hypothesized that, in the absence of Cbk1, Psc1 negatively regulates CO₂ tolerance by binding to and interfering with the function of mRNAs required for CO₂ tolerance. Supporting this model, we found that multiple mRNAs that are required for CO₂ tolerance associate with Psc1 in the absence of Cbk1. Furthermore, the transcripts of <i>ZDS3</i>, a gene required for CO₂ tolerance, predominantly colocalize with Psc1, which forms condensates in the <i>cbk1</i>Δ mutant at high CO₂, correlating with impaired growth. Collectively, our findings support the conclusion that <i>C. neoformans</i> adapts to high CO₂ through a post-transcriptional mechanism where Cbk1 phosphorylates Psc1, preventing its binding to, and subsequent functional inhibition of, mRNAs important for CO₂ tolerance.IMPORTANCEHigh CO₂ is growth-inhibitory, and therefore adaptation to high CO₂ stress is a universal cellular phenomenon required for survival. The environmental fungus, <i>Cryptococcus neoformans</i>, encounters high CO₂ environments in the host, and thus tolerance to high CO₂ is critical for its ability to cause lethal infections. The regulation of <u>A</u>ce2p and morphogenesis (RAM) pathway is required for its growth in high CO₂. We found that CO₂ tolerance is mediated post-transcriptionally by a downstream target of the RAM pathway, the RNA-binding protein Psc1. In the absence of the RAM pathway, Psc1 sequesters mRNA transcripts required for growth in high CO₂, preventing growth. These findings reveal a previously uncharacterized post-transcriptional regulatory mechanism that controls cryptococcal adaptation to high CO₂.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0205126"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The high protection of a novel chemo-attenuated sporozoite vaccine requires IL-15-mediated liver CD8⁺ tissue-resident memory T-cell responses.","authors":"Nie Tan, Chengyu Zhu, Teyang Li, Shubin Su, Shiming Jiao, Yuanli Gao, Yan Ding, Taiping Liu, Wenyue Xu","doi":"10.1128/mbio.01131-26","DOIUrl":"10.1128/mbio.01131-26","url":null,"abstract":"<p><p>Chemo-attenuated sporozoite vaccines (SPZ-CVacs) are considered promising for malaria prevention, but safety concerns persist regarding antimalarial drugs targeting either liver- or blood-stage parasites. In this study, we found that nitroquine (CI-679), used to eliminate malaria blood-stage parasites, effectively rendered sporozoites attenuated by arresting late liver-stage development. A single vaccination with CI-679-attenuated <i>Plasmodium berghei</i> (<i>P. berghei</i>) sporozoites conferred robust protection against sporozoite challenge in BALB/c mice. Using mouse models with distinct genetic backgrounds, we demonstrated that the robust protection conferred by the CI-679-attenuated vaccine was primarily associated with the frequency of parasite-specific CD8⁺ tissue-resident memory (Trm) cells mediated by IL-15. Notably, the supplement of IL-15/IL-15Ra sushi complex remarkably increased Trm frequency and improved the protective efficacy of CI-679-attenuated vaccine. Our findings characterize a novel SPZ-CVac and provide mechanistic evidence supporting IL-15 as an adjuvant to enhance the efficacy of pre-erythrocytic stage vaccines.IMPORTANCEMalaria remains a devastating global disease. Chemo-attenuated sporozoite vaccines show promise, yet safety concerns persist as current drugs target only liver- or blood-stage parasites. Here, we found nitroquine (CI-679) has a potentially favorable safety profile because of its dual liver- and blood-stage activity, and a single vaccination with CI-679-attenuated <i>P. berghei</i> sporozoites conferred robust protection against sporozoite challenge in BALB/c mice. Mechanistically, protection was associated with IL-15-mediated parasite-specific CD8⁺ tissue-resident memory (Trm) cells. Notably, the supplement of IL-15/IL-15Ra sushi complex remarkably increased Trm frequency and enhanced protective efficacy. Therefore, we characterize a novel chemo-attenuated sporozoite vaccine and provide mechanistic evidence supporting IL-15 as an adjuvant for pre-erythrocytic stage vaccines.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0113126"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal antibodies raised against the Junín virus glycoprotein show broad reactivity and provide protection <i>in vivo</i>.","authors":"Garazi Pena Alzua, Sharon Jan, Fatima Amanat, Grecia A Sandoval, Christopher A Sumner, Stephen Won, Anna L Lara, Anupama Sinha, Brooke N Harmon, Elizabeth B Allmon, Kendra J Alfson, Yenny Goez-Gazi, John W Dutton, Ricardo Carrion, Sneha Rangarajan, Melissa C Kerzic, Carter A Mitchell, Chris M Cirimotich, Dylan M Johnson, Florian Krammer","doi":"10.1128/mbio.00214-26","DOIUrl":"10.1128/mbio.00214-26","url":null,"abstract":"<p><p>Argentine hemorrhagic fever (AHF) is a disease caused by the Junín virus (JUNV) that can be fatal in 15%-30% of untreated cases. Although JUNV is the only arenavirus for which efficient therapy and vaccination have been established, its administration is limited. In this study, hybridoma technology was used to generate 30 mouse monoclonal antibodies (mAbs) against the glycoprotein complex (GPC) of JUNV. Of these 30 mAbs, 26 showed strong cross-binding to GPCs from various arenaviruses. In addition, nine mAbs demonstrated potent neutralizing activity <i>in vitro</i> with a 50% inhibitory concentration of less than 1 µg/mL against a replication-competent chimeric vesicular stomatitis virus expressing JUNV GPC (rVSV-JUNV), as well as the live attenuated JUNV vaccine strain Candid#1. Furthermore, when tested <i>in vivo</i> using a challenge model of rVSV-JUNV in Stat2^-/- mice, five select mAbs significantly reduced viral loads in the spleen when administered prophylactically. Humanized versions of JUNV-1A2, JUNV-1D5, and JUNV-5B12 mAbs, which showed protection <i>in vivo</i> in the Stat2^-/- surrogate model, were produced. These antibodies were evaluated in a guinea pig challenge model of AHF and showed protective efficacy. Escape experiments with these humanized antibodies, as well as previously characterized antibodies, GB03 and JUN1, using rVSV-JUNV resulted in the acquisition of amino acid changes in the GP1 part of the GPC, which directly contacts host receptor transferrin receptor 1, indicating these sites could be key for future therapies. In summary, we generated mAbs that may be valuable for antibody-guided vaccine design and therapeutic development.</p><p><strong>Importance: </strong>Junín virus (JUNV) is a highly pathogenic virus that causes Argentine hemorrhagic fever (AHF) and is classified as a category A pathogen due to its potential for aerosol transmission and the significant number of annual infections and deaths associated with it. Although effective treatments exist, such as convalescent immune plasma, their availability is limited, and they are ineffective when given after the first week of symptoms. This study is significant because it focuses on developing therapeutic monoclonal antibodies against JUNV with strong <i>in vitro</i> neutralizing activity and protection in both a surrogate mouse model and a guinea pig challenge model of AHF. This has led to promising antibody candidates that could be used as therapeutics to combat ongoing outbreaks.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0021426"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pangolin-derived sarbecoviruses show attenuated pathogenicity and transmissibility compared with SARS-CoV-2 in human ACE2 transgenic hamsters.","authors":"Hao-Feng Lin, Ren-Di Jiang, Li-Na Ji, Jin-Wei Zhang, Qian-Chun Gong, Hao-Rui Si, Yuan-Sen Shi, Xin-Hua Lin, Chen Qiu, Jian-Min Li, Mei-Qin Liu","doi":"10.1128/mbio.01843-26","DOIUrl":"10.1128/mbio.01843-26","url":null,"abstract":"<p><p>Genetic diversity of sarbecoviruses phylogenetically related to SARS-CoV-2 has been identified in Malayan pangolins. However, their potential pathogenicity and risk of cross-species transmission to humans remain largely unknown. In the present study, we performed comparative characterization of SARS-CoV-2 and two pangolin SARS-CoV-2-related viruses, named MpCoV-GD and MpCoV-GX, respectively, in human cell lines and organoids and human ACE2 (hACE2) transgenic hamsters. The cell-to-cell fusion assay showed that the Spike (S) protein of MpCoV-GD induces a stronger membrane fusion than the MpCoV-GX S protein, though weaker than the SARS-CoV-2 S protein. In human cells and organoids, both MpCoV-GX and MpCoV-GD replicated well but less efficiently than SARS-CoV-2. In K18-hACE2 hamsters, MpCoV-GD induced lung pathology comparable to SARS-CoV-2 by showing extensive damage to the alveolar parenchyma, while MpCoV-GX mainly caused alveolar wall thickening due to mild inflammatory cell infiltration. Similar to SARS-CoV-2, the two pangolin coronaviruses were capable of transmitting through direct contact and aerosol exposure, but their infectivity was largely attenuated during aerosol transmission. This study expands our understanding of the biological and infection features of the pangolin-derived sarbecoviruses. It demonstrates that current SARS-CoV-2-related therapeutics and pre-existing immunity can elicit cross-protection against the pangolin sarbecoviruses. Although their pathogenicity and transmissibility are relatively low, our findings suggest the necessity of continuing sarbecovirus surveillance in pangolins and other wildlife for prevention of future disease emergence.IMPORTANCEPangolin-derived sarbecoviruses capable of infecting human cells underscore the role of wildlife as reservoirs for potential zoonotic emergence. MpCoV-GD induces lung pathology comparable to SARS-CoV-2 in hACE2 hamsters, highlighting the need for proactive assessment of novel coronaviruses. Although aerosol transmission of MpCoV-GD and MpCoV-GX is attenuated, their ability to spread via direct contact and airborne routes indicates a tangible risk of cross-species transmission. Importantly, cross-neutralizing activity or inhibition conferred by existing SARS-CoV-2 immunity and therapeutics suggests that current preparedness strategies may help mitigate their impact. These findings reinforce the necessity of sustained surveillance of sarbecoviruses in pangolins and other wildlife to enable early detection and prevention of future outbreaks with significant public health consequences.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0184326"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building better microbial infection models: a call to do the \"field\" experiments.","authors":"Marvin Whiteley","doi":"10.1128/mbio.01768-26","DOIUrl":"10.1128/mbio.01768-26","url":null,"abstract":"<p><p>Experimental model systems are essential in microbiology. However, models are often described as \"biologically relevant\" without a clear explanation of what that means or how relevance was established. Here, I argue that the missing piece in model development is benchmarking. New technologies and increasingly elaborate model systems can be powerful, but they do not guarantee that a model better represents the environment it is meant to reproduce. The guarantee that is implied cannot be made explicit until these models are evaluated against measurements of microbial behavior and function made directly in those environments. These \"field\" experiments are often messy, expensive, low throughput, and technically challenging, but provide the benchmarks needed to determine what a model captures, what it misses, and which questions it can tackle. While chemical measurements and quantification of physical features can guide model construction, the most important readout is the behavior of the microbes in the natural environment.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0176826"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental evolution reveals contrasting adaptive landscapes in lab and field environments.","authors":"Alexander B Chase, Zhao Wang, Claudia Weihe, Steven D Allison, Jennifer B H Martiny","doi":"10.1128/mbio.01700-26","DOIUrl":"10.1128/mbio.01700-26","url":null,"abstract":"<p><p>Experimental evolution is widely used to infer microbial responses to environmental change, yet most laboratory studies impose constant, well-mixed conditions that differ fundamentally from fluctuating, spatially structured field environments. We compared genomic evolution in the leaf litter-associated bacterium <i>Curtobacterium</i> strain MMLR14_002 under control and warming treatments in laboratory culture and in a complementary field experiment. Laboratory-derived isolates accumulated more mutations per genome and exhibited stronger locus-level parallelism, with mutations recurring in a small number of coding loci. Field-derived isolates accumulated fewer mutations per genome, and these mutations rarely occurred in the same coding loci across replicate populations. Instead, field isolates exhibited a higher proportion of intergenic mutations, with mutations recurring in the same intergenic regions across independent field deployments. When coding mutations were detected in the field, they were distributed across functionally diffuse targets and more often involved metabolic pathways than the core cellular processes repeatedly targeted during laboratory evolution. Warming itself did not consistently influence mutation accumulation or the genomic distribution of mutations; instead, laboratory and field contexts primarily shaped the accumulation, targets, and repeatability of genomic change. These results suggest that laboratory thermal evolution identifies adaptive routes favored under sustained selection but may overestimate coding-level parallelism under heterogeneous field conditions. Bridging laboratory and field evolution will likely require experimental designs that incorporate temporal variability and spatial heterogeneity characteristic of natural systems.IMPORTANCEA central goal of experimental evolution is to infer how microbes evolve in nature from laboratory studies. Here, we evaluate this assumption by comparing genomic evolution of a leaf litter-associated <i>Curtobacterium</i> strain in laboratory and field warming experiments to identify broad patterns rather than isolate the contribution of any single environmental factor. We find that the strong parallelism at coding loci observed under laboratory conditions is reduced in the field, while mutations recurring in the same intergenic regions across field deployments suggest that parallel evolution in nature may more often involve regulatory noncoding regions rather than coding targets. These results show that environmental context reshapes adaptive landscapes and may limit the parallelism of coding-level genomic responses inferred from homogeneous laboratory conditions.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0170026"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}