{"title":"Type I interferons give gonococci a sweet treat and a chance at survival","authors":"Joseph P. Dillard","doi":"10.1016/j.chom.2025.05.019","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.019","url":null,"abstract":"In this issue, Kurt-Jones et al. demonstrate a surprising role for the type I interferon, IFN-ε, in <em>Neisseria gonorrhoeae</em> infections of the female reproductive tract. Rather than protecting the host, IFN-ε increases CMP-sialic acid production in epithelial cells, potentiating sialic acid modification of bacterial lipooligosaccharide, enabling innate immune evasion.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"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":"144586953","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":"Fungal cues, fibrotic consequences: Commensal sensing by alveolar macrophages promotes pulmonary fibrosis","authors":"Paul J. Brennan, Darin L. Wiesner","doi":"10.1016/j.chom.2025.06.015","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.015","url":null,"abstract":"In a recent issue of <em>Immunity</em>, Qiu et al. uncover a pivotal role for commensal fungi in promoting lung fibrosis, showing that their interaction with alveolar macrophages triggers a profibrotic transcriptional program through an unconventional Dectin-1-Raf1 signaling axis.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"109 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586950","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}
Ming Liu, Heng Wang, Zhao Wang, Hao Wang, Kuo Zhang, Juan Xue, Ronghui Liu, Ying Liu, Peiyi Xia, Hui Wang, Biao Kan, Yi Li, Shan Li, Yang Fu
{"title":"A Vibrio-specific T6SS effector reshapes microbial competition by disrupting Vibrio bioenergetics","authors":"Ming Liu, Heng Wang, Zhao Wang, Hao Wang, Kuo Zhang, Juan Xue, Ronghui Liu, Ying Liu, Peiyi Xia, Hui Wang, Biao Kan, Yi Li, Shan Li, Yang Fu","doi":"10.1016/j.chom.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.001","url":null,"abstract":"Type VI secretion systems (T6SSs) are widely distributed among <em>Vibrio</em> species, yet their roles in the coexistence of toxigenic and non-toxigenic strains remain unclear. Here, we report an orphan T6SS effector-immunity module, T6SS effector specific to <em>Vibrios</em> (TseVs)-cognate immunity protein (TsiVs), primarily harbored by non-toxigenic <em>Vibrio cholerae</em>. TseVs exhibits robust vibriocidal activity, specifically targeting susceptible <em>Vibrios</em> lacking the TsiVs. TseVs forms dual-membrane, ion-selective pores that collapse Na<sup>+</sup>/K<sup>+</sup> homeostasis, resulting in membrane depolarization and ATP depletion. Remarkably, non-<em>Vibrio</em> bacteria evade TseVs through proton motive force (PMF)-dependent resilience, uncovering an immunity-independent defense strategy. Furthermore, <em>tseVs</em>-positive non-toxigenic <em>V. cholerae</em> strains are globally distributed and have dominated in recent decades, highlighting TseVs’s ecological significance in <em>Vibrio</em> population dynamics. By linking TseVs bioenergetic targeting mechanisms to <em>Vibrio</em> population shifts, we demonstrate how T6SS effectors shape microbial genetic diversity. Our findings suggest that TseVs represents a promising model for precision antimicrobial strategies, minimizing collateral damage to commensal microbiota.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"27 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516209","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":"Immune profiling in subclinical secondary dengue-infected cases reveals adaptive immune signatures correlated to protection from severe dengue","authors":"Giorgio Gonnella, Valentina Libri, Emanuele Gioacchino, Sébastien Mella, Sotheary Sann, Sopheak Sorn, Sreymom Ken, Valerie Seffer, Nisa Ya, Leangyi Heng, Chantana Yay, Anavaj Sakuntabhai, Sowath Ly, Philippe Dussart, Veasna Duong, Milena Hasan, Tineke Cantaert","doi":"10.1016/j.chom.2025.06.006","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.006","url":null,"abstract":"Development of strategies to prevent severe dengue has been challenging, partly by our incomplete understanding of a protective immune response after dengue virus (DENV) infection. To define adaptive immune signatures associated with protection from hospitalized dengue, we performed in-depth single-cell immunoprofiling and quantified DENV-specific T cells in subclinical or hospitalized dengue-infected children. Individuals with subclinical infection exhibit clonally expanded CD4<ce:sup loc=\"post\">+</ce:sup> TEMRA cells, increased frequency of DENV-specific CD4<ce:sup loc=\"post\">+</ce:sup> T cells, and demonstrate a gene expression signature of increased Treg functionality. Across all T cell subsets, subclinical cases upregulated a type I IFN response gene signature. In contrast, expanding CD8<ce:sup loc=\"post\">+</ce:sup> EM cells from hospitalized patients express more inhibitory markers and fewer cytotoxic proteins. In addition, hospitalized dengue is characterized by high frequencies and clonally expanded immunoglobulin G (Ig)G1-expressing plasmablasts. These findings identify candidate correlates of protection and support a rationale for T cell-directed interventions for dengue disease.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"48 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504565","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}
Kendrew K. Wong, Benjamin G. Wu, Matthew Chung, Qinsheng Li, Fares Darawshy, Jun-Chieh J. Tsay, Meredith Holub, Clea R. Barnett, Benjamin Kwok, Matthias C. Kugler, Cecilia Chung, Jake G. Natalini, Shivani Singh, Yonghua Li, Rosemary Schluger, Lia Ficaro, Joseph Carpenito, Destiny Collazo, Luisanny Perez, Yaa Kyeremateng, Imran Sulaiman
{"title":"Microbial contribution to metabolic niche formation varies across the respiratory tract","authors":"Kendrew K. Wong, Benjamin G. Wu, Matthew Chung, Qinsheng Li, Fares Darawshy, Jun-Chieh J. Tsay, Meredith Holub, Clea R. Barnett, Benjamin Kwok, Matthias C. Kugler, Cecilia Chung, Jake G. Natalini, Shivani Singh, Yonghua Li, Rosemary Schluger, Lia Ficaro, Joseph Carpenito, Destiny Collazo, Luisanny Perez, Yaa Kyeremateng, Imran Sulaiman","doi":"10.1016/j.chom.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.002","url":null,"abstract":"Variations in the airway microbiome are associated with inflammatory responses in the lung and pulmonary disease outcomes. Regional changes in microbiome composition could have spatial effects on the metabolic environment, contributing to differences in the host response. Here, we profiled the respiratory microbiome (metagenome/metatranscriptome) and metabolome of a patient cohort, uncovering topographical differences in microbial function, which were further delineated using isotope probing in mice. In humans, the functional activity of taxa varied across the respiratory tract and correlated with immunomodulatory metabolites such as glutamic acid/glutamate and methionine. Common oral commensals, such as <em>Prevotella</em>, <em>Streptococcus</em>, and <em>Veillonella</em>, were more functionally active in the lower airways. Inoculating mice with these commensals led to regional increases in several metabolites, notably methionine and tyrosine. Isotope labeling validated the contribution of <em>Prevotella melaninogenica</em> in generating specific metabolites. This functional characterization of microbial communities reveals topographical changes in the lung metabolome and potential impacts on host responses.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"17 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488373","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}
Marina Mahler, Liang Cui, Leah M. Smith, Katharina G. Wandera, Oliver Dietrich, David Mayo-Muñoz, Seetharamsing Balamkundu, Megan En Lee, Hong Ye, Chuan-Fa Liu, Junzhou Wu, Juby Mathew, Jeremy Dubrulle, Lucia M. Malone, Simon A. Jackson, Antony J. Fairbanks, Peter C. Dedon, Stan J.J. Brouns, Peter C. Fineran
{"title":"Phage arabinosyl-hydroxy-cytosine DNA modifications result in distinct evasion and sensitivity responses to phage defense systems","authors":"Marina Mahler, Liang Cui, Leah M. Smith, Katharina G. Wandera, Oliver Dietrich, David Mayo-Muñoz, Seetharamsing Balamkundu, Megan En Lee, Hong Ye, Chuan-Fa Liu, Junzhou Wu, Juby Mathew, Jeremy Dubrulle, Lucia M. Malone, Simon A. Jackson, Antony J. Fairbanks, Peter C. Dedon, Stan J.J. Brouns, Peter C. Fineran","doi":"10.1016/j.chom.2025.06.005","DOIUrl":"https://doi.org/10.1016/j.chom.2025.06.005","url":null,"abstract":"Bacteria encode diverse anti-phage systems, such as CRISPR-Cas and restriction modification (RM), which limit infection by targeting phage DNA. We identified a DNA modification in phages, i.e., 5-arabinosyl-hydroxy-cytosine (5ara-hC), which adds arabinose to cytosines via a hydroxy linkage and protects phage from DNA targeting. The hydroxy linkage was common among arabinoslyated phages, with some arabinosylated phages encoding arabinose-5ara-hC transferases (Aat) that add a second or third arabinose to DNA. DNA arabinosylation enables evasion from DNA-targeting type I CRISPR-Cas and type II RM systems. However, arabinosylated phages remain sensitive to RNA-targeting CRISPR-Cas (type III and VI) and promiscuous type IV restriction endonucleases. 5ara-hC enables evasion of glycosylase defenses that target phages with glucosylated hydroxymethyl cytosines, and 5ara-ara-hC protects against some defenses capable of targeting 5ara-hC-modified phages. Collectively, this work identifies DNA modifications that enable phages to evade multiple defenses yet remain vulnerable to some systems that target RNA or modified nucleobases.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"43 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488376","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}
Andrea Anaya-Sanchez, Samuel B. Berry, Scott Espich, Alex Zilinskas, Phuong M. Tran, Carolina Agudelo, Helia Samani, K. Heran Darwin, Daniel A. Portnoy, Sarah A. Stanley
{"title":"Methylglyoxal is an antibacterial effector produced by macrophages during infection","authors":"Andrea Anaya-Sanchez, Samuel B. Berry, Scott Espich, Alex Zilinskas, Phuong M. Tran, Carolina Agudelo, Helia Samani, K. Heran Darwin, Daniel A. Portnoy, Sarah A. Stanley","doi":"10.1016/j.chom.2025.05.026","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.026","url":null,"abstract":"Infected macrophages transition into aerobic glycolysis, a metabolic program crucial for controlling bacterial infection. However, antimicrobial mechanisms supported by aerobic glycolysis are unclear. Methylglyoxal is a highly toxic aldehyde that modifies proteins and DNA and is produced as a side product of glycolysis. We show that despite this toxicity, infected macrophages generate high levels of methylglyoxal during aerobic glycolysis while downregulating the detoxification system, including glyoxalase 1 (GLO1). Dampening methylglyoxal generation in mice resulted in enhanced survival of <em>Listeria monocytogenes</em> and <em>Mycobacterium tuberculosis</em>, whereas mice lacking <em>Glo1</em> have increased methylglyoxal levels and improved infection control. Furthermore, bacteria unable to detoxify methylglyoxal (Δ<em>gloA</em>) exhibit attenuated virulence but are partially rescued in mice that cannot enter glycolysis and generate methylglyoxal. This loss of bacterial GloA results in up to a 1,000-fold greater genomic mutation frequency during infection. Collectively, these results suggest that methylglyoxal is an antimicrobial innate effector that defends against bacterial pathogens.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"12 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341356","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}
Joan Roncero-Carol, June Olaizola-Muñoa, Begoña Arán, Loris Sebastiano Mularoni, Marta Miret Cuesta, Nuria Blanco-Cabra, Marc Casals, Mireia Rumbo, Miquel Solé Inarejos, Samuel Ojosnegros, Berta Alsina, Eduard Torrents, Anna Veiga, Manuel Irimia, Esteban Hoijman
{"title":"Epithelial cells provide immunocompetence to the early embryo for bacterial clearance","authors":"Joan Roncero-Carol, June Olaizola-Muñoa, Begoña Arán, Loris Sebastiano Mularoni, Marta Miret Cuesta, Nuria Blanco-Cabra, Marc Casals, Mireia Rumbo, Miquel Solé Inarejos, Samuel Ojosnegros, Berta Alsina, Eduard Torrents, Anna Veiga, Manuel Irimia, Esteban Hoijman","doi":"10.1016/j.chom.2025.05.025","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.025","url":null,"abstract":"Early embryos are exposed to environmental perturbations that may influence their development, including bacteria. Despite lacking a proper immune system, the surface epithelium of early embryos (trophectoderm in mammals) can phagocytose defective pluripotent cells. Here, we explore the dynamic interactions between early embryos and bacteria. Quantitative live imaging of infection models developed in zebrafish embryos reveals the efficient phagocytic capability of surface epithelia in detecting, ingesting, and destroying infiltrated <em>E. coli</em> and <em>S. aureus</em>. <em>In vivo</em> single-cell interferences uncover actin-based epithelial zippering protrusions mediating bacterial phagocytosis, safeguarding developmental robustness upon infection. Transcriptomic and inter-scale dynamic analyses of phagocyte-bacteria interactions identify specific features of this epithelial phagocytic program. Notably, live imaging of mouse and human blastocysts supports a conserved role of the trophectoderm in bacterial phagocytosis. This defensive role of the surface epithelium against bacterial infection provides immunocompetence to early embryos, with relevant implications for understanding failures in human embryogenesis.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"5 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311934","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}
Stephany Flores Ramos, Nicole Siguenza, Wuling Zhong, Ipsita Mohanty, Amulya Lingaraju, R. Alexander Richter, Smruthi Karthikeyan, April L. Lukowski, Qiyun Zhu, Wilhan D.G. Nunes, Jasmine Zemlin, Zhenjiang Zech Xu, Jeff Hasty, Pieter C. Dorrestein, Satchidananda Panda, Rob Knight, Amir Zarrinpar
{"title":"Metatranscriptomics uncovers diurnal functional shifts in bacterial transgenes with profound metabolic effects","authors":"Stephany Flores Ramos, Nicole Siguenza, Wuling Zhong, Ipsita Mohanty, Amulya Lingaraju, R. Alexander Richter, Smruthi Karthikeyan, April L. Lukowski, Qiyun Zhu, Wilhan D.G. Nunes, Jasmine Zemlin, Zhenjiang Zech Xu, Jeff Hasty, Pieter C. Dorrestein, Satchidananda Panda, Rob Knight, Amir Zarrinpar","doi":"10.1016/j.chom.2025.05.024","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.024","url":null,"abstract":"Diurnal rhythmicity in the gut maintains gut integrity, circadian rhythms, and metabolic homeostasis. However, existing studies focus on microbial composition rather than transcriptional activity. To understand microbial functional dynamics, we characterize diurnal fluctuations in the mouse cecal metatranscriptome and metagenome under high-fat diet and time-restricted feeding (TRF). We show that metatranscriptomics uncovers TRF-induced time-dependent microbial functional shifts that are undetectable with metagenomics alone. We also found bile salt hydrolase (<em>bsh</em>) from <em>Dubosiella newyorkensis</em> exhibits diurnal expression in the TRF group. Engineering this <em>bsh</em>, along with other candidates, into a native <em>E. coli</em> chassis reveals distinct differences in deconjugation and amidation activities, underscoring functional specificity. <em>In vivo</em>, a <em>D. newyorkensis bsh</em> improves insulin sensitivity, glucose tolerance, and body composition, suggesting a direct role in TRF metabolic benefits. This study highlights how coupling metatranscriptomics with engineered bacterial systems is a powerful approach for uncovering time-dependent bacterial functions related to health and disease.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"183 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311935","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-Lucia Cabello, Kelsey Wells, Wenjing Peng, Hui-Qiang Feng, Junyao Wang, Damien F. Meyer, Christophe Noroy, En-Shuang Zhao, Hao Zhang, Xueqing Li, Haowu Chang, Gabriel Gomez, Min Wan, Yuxin Mao, Kristin L. Patrick, Robert O. Watson, William K. Russell, Aiying Yu, Jieqiang Zhong, Fengguang Guo, Paul de Figueiredo
{"title":"Brucella-driven host N-glycome remodeling controls infection","authors":"Ana-Lucia Cabello, Kelsey Wells, Wenjing Peng, Hui-Qiang Feng, Junyao Wang, Damien F. Meyer, Christophe Noroy, En-Shuang Zhao, Hao Zhang, Xueqing Li, Haowu Chang, Gabriel Gomez, Min Wan, Yuxin Mao, Kristin L. Patrick, Robert O. Watson, William K. Russell, Aiying Yu, Jieqiang Zhong, Fengguang Guo, Paul de Figueiredo","doi":"10.1016/j.chom.2025.05.023","DOIUrl":"https://doi.org/10.1016/j.chom.2025.05.023","url":null,"abstract":"(Cell Host & Microbe <em>32</em>, 588–605.e1–e9; April 10, 2024)","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"605 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305426","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}
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