Jackie Chen, Erick D. Nilsen, Chutikarn Chitboonthavisuk, James E. Corban, Matthew Yang, Charlie Y. Mo, Srivatsan Raman
{"title":"Systematic, high-throughput characterization of bacteriophage gene essentiality on diverse hosts","authors":"Jackie Chen, Erick D. Nilsen, Chutikarn Chitboonthavisuk, James E. Corban, Matthew Yang, Charlie Y. Mo, Srivatsan Raman","doi":"10.1016/j.chom.2025.06.018","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.018","url":null,"abstract":"Understanding core and conditional gene essentiality is crucial for decoding genotype-phenotype relationships in organisms. We present phage high-throughput approach for gene essentiality mapping and profiling (PhageMaP), a high-throughput method to create genome-scale loss-of-function libraries for systematically assessing gene essentiality in bacteriophages. Using PhageMaP across diverse hosts, we generate gene essentiality maps for all or most genes in the model phages T7 and T4, as well as the non-model phage Bas63. These maps provide fundamental insights into genome organization, gene function, and host-specific conditional essentiality. By applying PhageMaP to a collection of anti-phage defense systems, we uncover phage genes that either inhibit or activate six defenses and offer mechanistic hypotheses. Furthermore, we engineer synthetic phages with enhanced infectivity by modular transfer of a PhageMaP-discovered defense inhibitor from Bas63 to T7. PhageMaP advances bacteriophage functional genomics and accelerates rational phage design for therapy.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"14 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metatranscriptomics catches gut microbes in the act","authors":"Kailin Liu, Yuhao Wang","doi":"10.1016/j.chom.2025.06.004","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.004","url":null,"abstract":"In this issue of <em>Cell Host & Microbe</em>, Flores Ramos et al.<span><span><sup>1</sup></span></span> employ metatranscriptomics to uncover diurnal microbial functional shifts in the gut microbiome driven by time-restricted feeding. Their work highlights the value of metatranscriptomics over metagenomics in capturing real-time microbial activity and guiding therapeutic bacterial engineering.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"8 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How hosts accurately command bacteria for gut health","authors":"Jianglin Zhang, Xianda Ma, Zheng Kuang","doi":"10.1016/j.chom.2025.06.008","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.008","url":null,"abstract":"Amid the vast “ocean” of gut microbes, how hosts distinguish and respond to specific symbionts remains elusive. In a recent issue of <em>Nature</em>, Yang et al. show that host APOL proteins selectively engage Bacteroidales to trigger outer membrane vesicle release, illuminating a host-microbe mutualism that sustains gut immune homeostasis.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"93 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pamela Ferretti, Maria M. Martignoni, Lisa C. McManus, Taom Sakal, Armun Liaghat, Bethany Stevens, Kyle J.-M. Dahlin, Lucas S. Souza, Zoe G. Cardon, Cynthia B. Silveira, Seth R. Bordenstein, Joan Roughgarden
{"title":"Theory of host-microbe symbioses: Challenges and opportunities","authors":"Pamela Ferretti, Maria M. Martignoni, Lisa C. McManus, Taom Sakal, Armun Liaghat, Bethany Stevens, Kyle J.-M. Dahlin, Lucas S. Souza, Zoe G. Cardon, Cynthia B. Silveira, Seth R. Bordenstein, Joan Roughgarden","doi":"10.1016/j.chom.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.001","url":null,"abstract":"Growing insight into microbial symbioses highlights the need to model these systems mathematically. We discuss three areas requiring theoretical advancement: nested ecology within a host or holobiont, holobiont population dynamics, and symbiont-mediated speciation. Developing the proposed frameworks will bridge theory and empirical findings, accelerating our understanding of host-microbe symbioses.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"89 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Waste as an antibacterial weapon","authors":"M. Maria Elgrail, Michael S. Glickman","doi":"10.1016/j.chom.2025.06.011","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.011","url":null,"abstract":"Intracellular pathogens neutralize and evade macrophage-intrinsic host defenses. In this issue of <em>Cell Host & Microbe</em>, Anaya-Sanchez et al. show that methylglyoxal, a metabolic byproduct of glycolysis, is part of the macrophage arsenal limiting <em>L. monocytogenes</em> and <em>M. tuberculosis</em> infections but is countered by pathogen expression of methylglyoxal detoxification enzymes.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"10 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Rita Costa, Daan F. van den Berg, Jelger Q. Esser, Halewijn van den Bossche, Nadiia Pozhydaieva, Konstantinos Kalogeropoulos, Stan J.J. Brouns
{"title":"Bacteriophage genomes encode both broad and specific counter-defense repertoires to overcome bacterial defense systems","authors":"Ana Rita Costa, Daan F. van den Berg, Jelger Q. Esser, Halewijn van den Bossche, Nadiia Pozhydaieva, Konstantinos Kalogeropoulos, Stan J.J. Brouns","doi":"10.1016/j.chom.2025.06.010","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.010","url":null,"abstract":"The evolutionary arms race between bacteria and bacteriophages drives rapid evolution of bacterial defense mechanisms with scattered distribution across genomes. We hypothesized that this variability in bacterial defense systems leads to equally variable counter-defense repertoires in phage genomes. Examining the variable regions in <em>Pseudomonas</em> model phages of the <em>Pbunavirus</em> genus revealed five anti-defense genes, including one inhibiting Druantia type III named DadIII-1, another targeting Thoeris type III named TadIII-1, one inhibiting Zorya type I named ZadI-1, and two related broad defense inhibitors named Bdi1 and Bdi2 targeting four defenses. A typical <em>Pbunavirus</em> encodes up to five known anti-defense genes, some inhibiting four unrelated defense systems with distinct nucleic-acid-targeting mechanisms. Structural homologs of broad-acting Bdi1 and Bdi2 are encoded across diverse phage taxa infecting multiple bacterial hosts. These findings show that phages face a variety of bacterial defenses, driving them to evolve both specific and general strategies to overcome these barriers.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"13 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huan Yu, Yang Du, Yuling He, Yifan Sun, Junfeng Li, Bo Jia, Jiale Chen, Xinya Peng, Tongtong An, Jianjie Li, Yujia Chi, Man Wang, Lihua Cao, Yidi Tai, Xiaoyu Zhai, Reyizha Nuersulitan, Sheng Li, Nan Wu, Jia Wang, Hongchao Xiong, Ziping Wang
{"title":"Lactate production by tumor-resident Staphylococcus promotes metastatic colonization in lung adenocarcinoma","authors":"Huan Yu, Yang Du, Yuling He, Yifan Sun, Junfeng Li, Bo Jia, Jiale Chen, Xinya Peng, Tongtong An, Jianjie Li, Yujia Chi, Man Wang, Lihua Cao, Yidi Tai, Xiaoyu Zhai, Reyizha Nuersulitan, Sheng Li, Nan Wu, Jia Wang, Hongchao Xiong, Ziping Wang","doi":"10.1016/j.chom.2025.06.013","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.013","url":null,"abstract":"The role of the lung microbiota in cancer remains unclear. Here, we reveal that <em>Staphylococcus</em> is selectively enriched in metastatic tumor lesions and is associated with tumor recurrence in lung cancer patients. Using patient-derived bacterial strains, we employ a combination of cell line, organoid, mouse allograft, and xenograft models to demonstrate that <em>S. nepalensis</em> and <em>S. capitis</em> promote the metastatic potential of lung cancer cells. Mechanistically, lactate secreted by <em>S. nepalensis</em> and <em>S. capitis</em> upregulates MCT1 expression in tumor cells, facilitating lactate uptake and activating pseudohypoxia signaling. These effects can be eliminated by knocking out the lactate-producing genes (D-lactate dehydrogenase [<em>ddh</em>]/L-lactate dehydrogenase [<em>ldh</em>]) in the bacterial strains. Furthermore, we show that inhibiting MCT1 attenuates <em>Staphylococcus</em>-induced tumor metastasis both <em>in vitro</em> and <em>in vivo</em>. Collectively, our results demonstrate that tumor-resident <em>Staphylococcus</em> species promote lung cancer metastasis by activating host pseudohypoxia signaling and further identify key regulators as potential targets for therapeutic development.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"2 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Upper vs. lower airways: Microbes shape the local milieu","authors":"Shifen Xu, Zhang Wang","doi":"10.1016/j.chom.2025.06.007","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.007","url":null,"abstract":"In this issue of <em>Cell Host & Microbe</em>, Wong et al. investigate the contribution of the microbiome to airway metabolism, revealing differential microbial pathways and metabolites between the upper and lower airways. Oral commensals contribute to the metabolic milieu with <em>Prevotella melaninogenica</em> synthesizing inosine and glutamate in the lower airways.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"10 3 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bugged before birth?: How maternal microbes reprogram offspring immunity","authors":"Madison S. Strine, Liza Konnikova","doi":"10.1016/j.chom.2025.06.003","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.003","url":null,"abstract":"Early-life microbial exposures can have long-lasting health impacts. In a recent <em>Cell</em> paper, Stevens et al. show that maternal antibiotic treatment induces dysbiosis and impairs offspring immunity to influenza. CD8<sup>+</sup> T cell dysfunction could be reversed with a <em>Bifidobacterium</em> metabolite, supporting a gut-lung immune axis that begins <em>in utero</em>.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"12 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A helping hand against severe dengue","authors":"Shirin Kalimuddin, Eng Eong Ooi","doi":"10.1016/j.chom.2025.06.012","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.012","url":null,"abstract":"What immune responses protect against severe dengue? In this issue of <em>Cell Host & Microbe</em>, Gonnella et al. find that early CD4<sup>+</sup> TEMRA cell expansion, enhanced regulatory T cell function, and type I IFN signatures in T cells are associated with protection, offering insights with implications for dengue vaccine development.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"21 6 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}