The ISME JournalPub Date : 2026-04-15DOI: 10.1093/ismejo/wrag093
Max Emil Schön, Christopher R Schvarcz, Silja V Malkewitz, Fanny C Hinner, Anna Koslová, Ulrike Mersdorf, Fiona Schimm, Sebastian Rickert, Nadiia Pozhydaieva, Kelsey McBeain, Thomas Hackl, Alina Cosima Schneider, Karina Barenhoff, Katharina Höfer, Kyle F Edwards, Grieg F Steward, Matthias G Fischer
{"title":"Strain-level diversity of giant viruses infecting chlorarachniophyte algae in the subtropical North Pacific","authors":"Max Emil Schön, Christopher R Schvarcz, Silja V Malkewitz, Fanny C Hinner, Anna Koslová, Ulrike Mersdorf, Fiona Schimm, Sebastian Rickert, Nadiia Pozhydaieva, Kelsey McBeain, Thomas Hackl, Alina Cosima Schneider, Karina Barenhoff, Katharina Höfer, Kyle F Edwards, Grieg F Steward, Matthias G Fischer","doi":"10.1093/ismejo/wrag093","DOIUrl":"https://doi.org/10.1093/ismejo/wrag093","url":null,"abstract":"Giant DNA viruses are ubiquitous among unicellular eukaryotes and occur in marine, freshwater, and terrestrial environments. Despite intense metagenomic data mining, their strain-level diversity remains largely unexplored. Here we introduce a model system comprising four isolates of a giant virus called ChlorV, which infects marine microalgae of the class Chlorarachniophyceae (Rhizaria) from station ALOHA, Hawai’i. The ChlorV genomes are 469 kbp to 493 kbp long and encode approximately 400 proteins, at least 106 of which are present in purified virions. Although the four viral genomes are highly syntenic, they differ by several insertions and deletions that often encode methyltransferases. We found that some of these methyltransferase genes correlated with specific DNA methylation patterns in the same ChlorV strain. Our study describes the first giant viruses infecting the eukaryotic supergroup Rhizaria and demonstrates how viral strain-level variation in gene content and epigenetic features may affect eco-evolutionary processes in marine microalgae.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147684760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2026-04-15DOI: 10.1093/ismejo/wrag094
Margaret A Vogel,Fragkiskos Machairas,Sophia Ferchiou,Jay Osvatic,Hanin Alzubaidy,Joana Séneca,Bela Hausmann,Katja Klun,Jillian M Petersen
{"title":"Symbiont diversity within Loripes orbiculatus and the case for multiple hosts.","authors":"Margaret A Vogel,Fragkiskos Machairas,Sophia Ferchiou,Jay Osvatic,Hanin Alzubaidy,Joana Séneca,Bela Hausmann,Katja Klun,Jillian M Petersen","doi":"10.1093/ismejo/wrag094","DOIUrl":"https://doi.org/10.1093/ismejo/wrag094","url":null,"abstract":"Seagrasses support immense biodiversity and are critical for maintaining coastal ecosystem health. These foundation species benefit from a 'three-way' facultative relationship with one of the common inhabitants of seagrass meadows, lucinid bivalves, which host specific bacterial Ca. Thiodiazotropha symbionts. Relatives of the bivalve symbionts have been detected on seagrass roots raising the possibility that these symbionts may colonize both animals and plants; however, no study has yet compared bivalve- and seagrass-associated symbionts at the same site and time. Our combination of 16S rRNA gene amplicon and metagenome sequencing revealed a greater diversity than was previously observed within both lucinid bivalves and on seagrass roots from the Adriatic Sea and resulted in the closed genome of one prominent symbiont species. We show that two of the Ca. Thiodiazotropha ASVs found on seagrass roots are identical to those found in bivalve hosts at the same site. This suggests that symbiont sharing may occur in the seagrass habitat between these two host species, which has important evolutionary and ecological implications for both hosts and symbionts.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2026-04-15DOI: 10.1093/ismejo/wrag095
Jinzhi Yang, Haowei Du, Fan Tao, Muhammad Atiq Ashraf, Xusheng Gao, Xue Huang, Kaijie Zhu, Guohuai Li, Jinshui Zheng, Paola Bonfante, Francesca Cardinale, Junwei Liu
{"title":"Rhizosphere microbial shifts drive amygdalin detoxification and jasmonate-mediated alleviation of peach autotoxicity","authors":"Jinzhi Yang, Haowei Du, Fan Tao, Muhammad Atiq Ashraf, Xusheng Gao, Xue Huang, Kaijie Zhu, Guohuai Li, Jinshui Zheng, Paola Bonfante, Francesca Cardinale, Junwei Liu","doi":"10.1093/ismejo/wrag095","DOIUrl":"https://doi.org/10.1093/ismejo/wrag095","url":null,"abstract":"Plant-associated microbes play essential roles in maintaining plant health and modulating responses to environmental stresses. Autotoxicity from allelopathic compounds is a major constraint on perennial crop production, yet the potential for plants to recruit microbiota to counteract such toxicity remains understudied. Our research combined field sampling from a multi-replant peach system, multi-omics, pot, and hydroponic experiments to elucidate plant-microbe interactions that alleviate amygdalin-induced autotoxicity. Metabolomic analysis of peach orchard soils showed that amygdalin accumulated progressively in the rhizosphere with longer continuous cultivation. Exogenous amygdalin inhibited plant growth, with stronger suppression observed in sterilized soil, suggesting a protective role of soil microbes. Amygdalin application altered rhizobacterial community structure and enriched several taxa, including Burkholderia-Caballeronia-Paraburkholderia and Sinomonas. In vitro assays confirmed that amygdalin serves as a selective substrate for these enriched bacteria. We further found that three strains isolated from the amygdalin-stressed peach rhizosphere significantly alleviated autotoxic inhibition, and their co-inoculation showed the greatest enhancement of plant performance. Metabolomic and transcriptomic analyses revealed activation of plant jasmonic acid (JA) pathway. Its involvement was confirmed by the alleviation of amygdalin-induced stress upon exogenous JA application and by the attenuation of microbiota-mediated stress relief upon JA pathway inhibition. Our study reveals a critical mechanism by which host plants enrich specialized microbes that can alleviate autotoxicity by direct amygdalin degradation, activation of the JA pathway, and modulation of redox homeostasis in peach. These findings provide new insights into plant-microbe interactions in perennial systems and highlight the potential of microbiome-informed microbial interventions for mitigating replant disease.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147684502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2026-04-14DOI: 10.1093/ismejo/wrag087
Jiamin Ai,Mingxia Ren,Ziwei Hao,Yuru Zhai,Entao Wang,Zhenshan Deng,Zhefei Li
{"title":"Bacillus populations restore amino acid metabolism in Mesorhizobium under saline-alkali stress to enhance nitrogen fixation efficiency.","authors":"Jiamin Ai,Mingxia Ren,Ziwei Hao,Yuru Zhai,Entao Wang,Zhenshan Deng,Zhefei Li","doi":"10.1093/ismejo/wrag087","DOIUrl":"https://doi.org/10.1093/ismejo/wrag087","url":null,"abstract":"The root nodules formed by rhizobia and leguminous plants are specialized structures for nitrogen fixation. However, a large number of non-rhizobial endophytes (NREs) also coexist within the nodules, and their contribution to nitrogen fixation under abiotic stress conditions remains unclear. Here, using the wild leguminous shrub Sophora davidii as model system, we identified an important NRE (Bacillus siamensis BT-9-1) by analyzing keystone taxa within the bacterial cooccurrence network of root nodules. This strain could improve the survival of Mesorhizobium metallidurans YC-39 under saline-alkali stress. A mechanistic investigation revealed that the expression of ilvA, ilvH, and ilvD was downregulated, and the contents of (2S)-isopropylmalate and succinic acid decreased in M. metallidurans YC-39 under saline-alkali conditions, whereas B. siamensis BT-9-1 presented increased accumulation of these metabolites. These findings indicate that B. siamensis BT-9-1 cross-feeds M. metallidurans YC-39 with these metabolites, rescuing the compromised branched-chain amino acid synthesis pathway and the TCA cycle in saline-alkali environments. Eventually, coinoculation with B. siamensis BT-9-1 and M. metallidurans YC-39, along with (2S)-isopropylmalate and succinic acid supplementation, increased nitrogenase activity of the symbionts. Our study reveals a novel mechanism by which non-rhizobial endophyte Bacillus species enhances the growth and nitrogen fixation efficiency of M. metallidurans under saline-alkali stress through the delivery of key metabolites.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2026-04-14DOI: 10.1093/ismejo/wrag090
Coline Meynard-Doumenc,Quentin Lamy-Besnier,Loïc Brot,Marie Messika,Auguste Wolfromm,Jean-Pierre Grill,Luisa De Sordi
{"title":"Oxidative stress constrains evolution of bacteriophage host-range diversity.","authors":"Coline Meynard-Doumenc,Quentin Lamy-Besnier,Loïc Brot,Marie Messika,Auguste Wolfromm,Jean-Pierre Grill,Luisa De Sordi","doi":"10.1093/ismejo/wrag090","DOIUrl":"https://doi.org/10.1093/ismejo/wrag090","url":null,"abstract":"Reactive oxygen species are essential for cellular signalling and redox homeostasis, but their accumulation causes cellular oxidative stress. In inflammatory bowel disease, oxidative stress is linked to chronic inflammation and alterations in the gut microbiota. We hypothesised that these alterations may result from the impact of reactive oxygen species on the interactions between bacteria and their viruses, bacteriophages. We followed the evolution of three Escherichia coli strains and a virulent bacteriophage in a chemostat under continuous growth and studied the impact of oxidative stress on this community. We show that both the bacteriophage and its three hosts persisted in the system over 10 days, but the relative abundance of bacteriophages was decreased in the presence of reactive oxygen species. Oxidative stress also limited bacteriophage population diversity by favouring the selection of specialist bacteriophages with a narrower host range. Concomitantly, reactive oxygen species accelerated the evolution of bacterial resistance to bacteriophages and drove the fixation of genomic mutations in genes related to cell surface structures or located in mobile genetic elements. These results highlight that oxidative stress impacts the evolutionary dynamics between bacteria and bacteriophages with consequences for microbiota diversity and potential implications in the context of intestinal inflammation.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2026-04-14DOI: 10.1093/ismejo/wrag088
Ji Zhan,Wei Yang,Junhui Guo,Yanshuang Yu,Shuyao Lai,Xing Liu,Shungui Zhou
{"title":"Iron plaques as terminal electron acceptors optimize clostridial fermentation and nitrogen fixation in rice rhizospheres.","authors":"Ji Zhan,Wei Yang,Junhui Guo,Yanshuang Yu,Shuyao Lai,Xing Liu,Shungui Zhou","doi":"10.1093/ismejo/wrag088","DOIUrl":"https://doi.org/10.1093/ismejo/wrag088","url":null,"abstract":"Fermentative Clostridium species associated with rice roots can contribute substantially to biological nitrogen fixation in anoxic paddy soils, yet whether their biological nitrogen fixation is regulated by the redox chemistry of rhizosphere remains unclear. Here we show that iron plaques on rice roots function as terminal electron acceptors that reprogram Clostridium fermentation and thereby enhance biological nitrogen fixation. In nitrogen-fixation microcosms, Clostridium sensu stricto I was selectively enriched under plaque-associated Fe(III)-reducing conditions, coinciding with elevated nitrogen fixation. Metabolomic profiling coupled with metabolic flux analysis revealed that Fe(III) reduction redirects a portion of carbon and electron flow from low-energy-yield solventogenesis toward high-energy-yield acidogenesis. This shift increases cellular ATP generation and expands the reductant pool, thereby benefiting the energetic and reductant demands of nitrogenase. Integrated transcriptomic and metagenomic analyses further identified NosR, a flavin mononucleotide-binding protein that is upregulated during Fe(III) reduction and may facilitate electron delivery to plaque-associated Fe(III). Our findings establish a mechanism in which iron plaque reduction optimizes fermentation for biological nitrogen fixation, providing fundamental insights into coupled Fe-N cycling in rice rhizospheres and suggesting potential strategies for sustainable nitrogen management in flooded agroecosystems.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"111 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2026-04-11DOI: 10.1093/ismejo/wrag083
Bo Zhao,Xingsheng Yang,Kai Feng,Jie Wang,Mingqian Liu,Yingcheng Wang,Danrui Wang,Xi Peng,Qing He,Yanjuan Lu,Hassan Waseem,Shang Wang,Ye Deng
{"title":"Phylogenetic assembly of methanogenesis regulates methane yield in food-waste anaerobic digestion.","authors":"Bo Zhao,Xingsheng Yang,Kai Feng,Jie Wang,Mingqian Liu,Yingcheng Wang,Danrui Wang,Xi Peng,Qing He,Yanjuan Lu,Hassan Waseem,Shang Wang,Ye Deng","doi":"10.1093/ismejo/wrag083","DOIUrl":"https://doi.org/10.1093/ismejo/wrag083","url":null,"abstract":"Anaerobic digestion (AD) of food waste (FW) is a key wate-to-energy strategy, yet daily biogas yield is often challenging to sustain, partly due to a limited understanding of the internal methanogens and their functional divergence. Here, we investigated seven full-scale mesophilic FW-AD systems distributed across China along a broad latitudinal gradient (>2,800 km), linking methane production variations (0.38-2.11 m3/m3•d-1) with the phylogenetic distributions of methanogens and their methanogenic genes. We found that hydrogenotrophic and aceticlastic pathways were ubiquitous, whereas methylotrophic methanogenesis showed regional enrichment in warmer regions, reflecting persistent influences of climate-associated upstream conditions on downstream methanogenic communities. Gene-level phylogeny of methanogenesis-related alleles, rather than species-level phylogeny, closely tracked biogas yield variation (Mantel's P < 0.05) and showed consistently stronger associations than gene-level compositions (mean standardized total effect: 0.491 vs. 0.298, P < 0.01). Higher methane yields (1.61 vs. 0.61 m3/m3•d-1 in high- vs. low-performing systems, P < 0.01) were significantly associated with reduced Faith's phylogenetic diversity (1.82 vs. 2.30, P < 0.01) and tighter clustering (mean pairwise phylogenetic distance, MPD: 0.25 vs. 0.30, P < 0.01) of methanogenic gene variants, suggesting that phylogenetic coherence may reflect ecological filtering favoring efficient methanogenesis, albeit at the expense of functional redundancy. These findings highlight gene-level trait phylogeny as a potential proxy for functional robustness, offering a framework for ecological design of AD microbiomes.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2026-04-11DOI: 10.1093/ismejo/wrag078
Alexander Mahnert,Maximilian Dreer,Ülkü Perier,Michael Melcher,Stefanie Duller,Adina Lehnen,Theodora Goessler,Daniela Brunner,Thomas Graier,Peter Wolf,Rafael I Ponce-Toledo,Logan H Hodgskiss,Melina Kerou,Christine Moissl-Eichinger,Christa Schleper
{"title":"Cultivation and Molecular Profiling Reveal Ammonia-Oxidizing Archaea as Skin Commensals.","authors":"Alexander Mahnert,Maximilian Dreer,Ülkü Perier,Michael Melcher,Stefanie Duller,Adina Lehnen,Theodora Goessler,Daniela Brunner,Thomas Graier,Peter Wolf,Rafael I Ponce-Toledo,Logan H Hodgskiss,Melina Kerou,Christine Moissl-Eichinger,Christa Schleper","doi":"10.1093/ismejo/wrag078","DOIUrl":"https://doi.org/10.1093/ismejo/wrag078","url":null,"abstract":"Ammonia-oxidizing archaea (AOA) have repeatedly been detected with molecular methods on human skin, yet their persistence, physiological traits, and adaptations remain poorly understood. This is mostly owed to a lack of cultured representatives of AOA taxa from healthy human skin. Using a customized enrichment scheme, we cultivated two autotrophic strains, Candidatus Nitrosocosmicus epidermidis and Ca. Nitrosocosmicus unguis, from human skin samples. Genomic analyses revealed specific adaptations for skin colonization, including genomic islands, and expanded gene families linked to interactions with host proteins, and signaling pathways, distinguishing these AOA from their soil-dwelling relatives. Profiling of more than 700 samples from 8 body sites in cross-sectional, and longitudinal cohorts consistently validated the detection of Nitrosocosmicus species with up to 100% prevalence in a longitudinal cohort, and particularly in sebaceous areas. Co-occurrence patterns with specific bacterial taxa reinforce their role as stable components of the skin microbiome. Our results establish Nitrosocosmicus species as common skin commensals, that are evolutionarily capable of transitioning from soil to human skin. They likely play a critical role in the skin ecosystem by recovering nitrogen from the sebum through utilisation of urea and ammonia. This sheds new light on the role of archaeal species in maintaining the nitrogen balance in the human skin microbiome which might be of importance maintaining a healthy skin.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"High-pathogenicity island enhances NDM-5 activity and drives global spread of Escherichia coli ST410.","authors":"Wanyun He,Jieying Tu,Zhongpeng Cai,Zixuan Wang,Chuying Liang,Yingbo Gao,Guolong Gao,Luchao Lv,Jun Yang,Yi-Yun Liu,Jianzhong Shen,Yang Wang,Jian-Hua Liu","doi":"10.1093/ismejo/wrag086","DOIUrl":"https://doi.org/10.1093/ismejo/wrag086","url":null,"abstract":"The international high-risk clone Escherichia coli ST410 poses a serious threat to clinical therapy and public health. By analyzing 3,434 ST410 genomes, we observed a broad ecological and geographic distribution along with frequent acquisition of the carbapenem resistance gene blaNDM-5 and a yersiniabactin-encoding high-pathogenicity island (HPI). We found that blaNDM-5 and HPI co-occurred in the most successful subclades. Functional assays comparing the wild-type strain with its isogenic mutant demonstrated that HPI augments bacterial iron uptake, promotes growth under iron-limited conditions, and increases pathogenicity in a mouse infection model. HPI also increases intracellular zinc levels and boosts NDM-5 β-lactamase activity, thereby improving bacterial survival under imipenem exposure in vitro and in mice. These findings suggest that the successful dissemination of ST410 is propelled by a synergy between HPI-mediated metal acquisition and blaNDM-5, linking enhanced virulence with elevated antibiotic resistance. This study provides mechanistic insight into resistance-virulence co-evolution in an emerging bacterial lineage and illustrates how ecological selection imposed by metal limitation and antibiotic exposure can jointly shape the success of high-risk clones across diverse ecosystems.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phage receptor specificity drives cross-resistance patterns and governs fitness trade-offs during sequential resistance acquisition in Salmonella.","authors":"Yingting Wu,Jing Yu,Weilai Tao,Jie Wu,Yumeng Gan,Yuxuan Wang,Xin Zhao,Xiaojing Hao,Qian Zhang,Hongning Wang,Anyun Zhang","doi":"10.1093/ismejo/wrag077","DOIUrl":"https://doi.org/10.1093/ismejo/wrag077","url":null,"abstract":"Phages infect bacteria by binding to specific surface receptors, driving co-evolution in microbial communities and offering therapeutic potential. However, how receptor specificity shapes the cross-resistance patterns and evolutionary trade-offs during phage-bacteria co-evolution remains unclear. Here, we investigated the genetic basis and fitness trade-offs of phage resistance in Salmonella to phages targeting O-antigen, core oligosaccharide, and BtuB (TonB-dependent receptor for vitamin B12) under individual or combinatorial pressures. The interaction matrices between phage-resistant strains and phages targeting three different receptors showed that bacterial cross-resistance to phages depends on the receptor type. Lipopolysaccharide (LPS) truncation conferred cross-resistance to phages targeting either the O-antigen or core oligosaccharide; whereas resistance to phages targeting BtuB occurred exclusively through mutations in the btuB gene. For LPS receptors whose biosynthesis involves multiple genes, the fitness cost associated with phage resistance is gene-specific. Among mutations conferring resistance to both O-antigen-targeting and core-targeting phages, those in the rfaJ gene exhibited the lowest fitness cost. The three-phage combination targeting three receptors exhibited potent antibacterial effects. Under this selective pressure, Salmonella developed resistance through receptor modification. Resistance to O-antigen-targeting and core-targeting phages emerged first through mutations in LPS biosynthesis genes, with mutations in the rfaJ gene dominating. Subsequently, mutations in the btuB gene accumulated to resist BtuB-targeting phages, ultimately evading predation by all three phages. Our results reveal receptor-driven evolutionary trade-offs and sequential resistance acquisition in Salmonella under multiple phages pressure, enhancing understanding of microbial interactions and informing phage therapy strategies.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}