{"title":"Comprehensive analysis of Mycobacterium tuberculosis genomes reveals genetic variations in bacterial virulence","authors":"Wittawin Worakitchanon, Hideki Yanai, Pundharika Piboonsiri, Reiko Miyahara, Supalert Nedsuwan, Worarat Imsanguan, Boonchai Chaiyasirinroje, Waritta Sawaengdee, Sukanya Wattanapokayakit, Nuanjan Wichukchinda, Yosuke Omae, Prasit Palittapongarnpim, Katsushi Tokunaga, Surakameth Mahasirimongkol, Akihiro Fujimoto","doi":"10.1016/j.chom.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.004","url":null,"abstract":"Tuberculosis, a disease caused by <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>), is a significant health problem worldwide. Here, we developed a method to detect large insertions and deletions (indels), which have been generally understudied. Leveraging this framework, we performed a comprehensive analysis of single nucleotide variants and small and large indels across 1,960 <em>Mtb</em> clinical isolates. Comparing the distribution of variants demonstrated that gene disruptive variants are underrepresented in genes essential for bacterial survival. An evolutionary analysis revealed that <em>Mtb</em> genomes are enriched in partially deleterious mutations. Genome-wide association studies identified small and large deletions in <em>eccB2</em> significantly associated with patient prognosis. Additionally, we unveil significant associations with antibiotic resistance in 23 non-canonical genes. Among these, large indels are primarily found in genetic regions of <em>Rv1216c</em>, <em>Rv1217c</em>, <em>fadD11</em>, and <em>ctpD</em>. This study provides a comprehensive catalog of genetic variations and highlights their potential impact for the future treatment and risk prediction of tuberculosis.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"35 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519560","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}
Minwoo Bae, Chi Le, Raaj S. Mehta, Xueyang Dong, Lindsey M. Pieper, Lorenzo Ramirez, Margaret Alexander, Sina Kiamehr, Peter J. Turnbaugh, Curtis Huttenhower, Andrew T. Chan, Emily P. Balskus
{"title":"Metatranscriptomics-guided discovery and characterization of a polyphenol-metabolizing gut microbial enzyme","authors":"Minwoo Bae, Chi Le, Raaj S. Mehta, Xueyang Dong, Lindsey M. Pieper, Lorenzo Ramirez, Margaret Alexander, Sina Kiamehr, Peter J. Turnbaugh, Curtis Huttenhower, Andrew T. Chan, Emily P. Balskus","doi":"10.1016/j.chom.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.002","url":null,"abstract":"Gut microbial catechol dehydroxylases are a largely uncharacterized family of metalloenzymes that potentially impact human health by metabolizing dietary polyphenols. Here, we use metatranscriptomics (MTX) to identify highly transcribed catechol-dehydroxylase-encoding genes in human gut microbiomes. We discover a prevalent, previously uncharacterized catechol dehydroxylase (<em>Gp</em> Hcdh) from <em>Gordonibacter pamelaeae</em> that dehydroxylates hydrocaffeic acid (HCA), an anti-inflammatory gut microbial metabolite derived from plant-based foods. Further analyses suggest that the activity of <em>Gp</em> Hcdh may reduce anti-inflammatory benefits of polyphenol-rich foods. Together, these results show the utility of combining MTX analysis and biochemical characterization for gut microbial enzyme discovery and reveal a potential link between host inflammation and a specific polyphenol-metabolizing gut microbial enzyme.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"33 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519563","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}
Deborah Häcker, Kolja Siebert, Byron J. Smith, Nikolai Köhler, Alessandra Riva, Aritra Mahapatra, Helena Heimes, Jiatong Nie, Amira Metwaly, Hannes Hölz, Quirin Manz, Federica De Zen, Jeannine Heetmeyer, Katharina Socas, Giang Le Thi, Chen Meng, Karin Kleigrewe, Josch K. Pauling, Klaus Neuhaus, Markus List, Dirk Haller
{"title":"Exclusive enteral nutrition initiates individual protective microbiome changes to induce remission in pediatric Crohn’s disease","authors":"Deborah Häcker, Kolja Siebert, Byron J. Smith, Nikolai Köhler, Alessandra Riva, Aritra Mahapatra, Helena Heimes, Jiatong Nie, Amira Metwaly, Hannes Hölz, Quirin Manz, Federica De Zen, Jeannine Heetmeyer, Katharina Socas, Giang Le Thi, Chen Meng, Karin Kleigrewe, Josch K. Pauling, Klaus Neuhaus, Markus List, Dirk Haller","doi":"10.1016/j.chom.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.001","url":null,"abstract":"Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn’s disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with <em>Lachnospiraceae</em> and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free <em>Il10</em>-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"97 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489634","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}
Virginia J. Glick, Cecilia A. Webber, Lauren E. Simmons, Morgan C. Martin, Maryam Ahmad, Cecilia H. Kim, Amanda N.D. Adams, Sunghee Bang, Michael C. Chao, Nicole C. Howard, Sarah M. Fortune, Manasvi Verma, Marco Jost, Lalit K. Beura, Michael J. James, Seo Yoon Lee, Caroline M. Mitchell, Jon Clardy, Ki Hyun Kim, Smita Gopinath
{"title":"Vaginal lactobacilli produce anti-inflammatory β-carboline compounds","authors":"Virginia J. Glick, Cecilia A. Webber, Lauren E. Simmons, Morgan C. Martin, Maryam Ahmad, Cecilia H. Kim, Amanda N.D. Adams, Sunghee Bang, Michael C. Chao, Nicole C. Howard, Sarah M. Fortune, Manasvi Verma, Marco Jost, Lalit K. Beura, Michael J. James, Seo Yoon Lee, Caroline M. Mitchell, Jon Clardy, Ki Hyun Kim, Smita Gopinath","doi":"10.1016/j.chom.2024.09.014","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.014","url":null,"abstract":"The optimal vaginal microbiome is a <em>Lactobacillus</em>-dominant community. Apart from <em>Lactobacillus iners</em>, the presence of <em>Lactobacillus</em> species is associated with reduced vaginal inflammation and reduced levels of pro-inflammatory cytokines. Loss of <em>Lactobacillus</em>-dominance is associated with inflammatory conditions, such as bacterial vaginosis (BV). We have identified that <em>Lactobacillus crispatus</em>, a key vaginal bacterial species, produces a family of β-carboline compounds with anti-inflammatory activity. These compounds suppress nuclear factor κB (NF-κB) and interferon (IFN) signaling downstream of multiple pattern recognition receptors in primary human cells and significantly dampen type I IFN receptor (IFNAR) activation in monocytes. Topical application of an anti-inflammatory β-carboline compound, perlolyrine, was sufficient to significantly reduce vaginal inflammation in a mouse model of genital herpes infection. These compounds are enriched in cervicovaginal lavage (CVL) of healthy people compared with people with BV. This study identifies a family of compounds by which vaginal lactobacilli mediate host immune homeostasis and highlights a potential therapeutic avenue for vaginal inflammation.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"31 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444187","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":"Gut symbiont-derived anandamide promotes reward learning in honeybees by activating the endocannabinoid pathway","authors":"Zhaopeng Zhong, Xiaohuan Mu, Haoyu Lang, Yueyi Wang, Yanling Jiang, Yuwen Liu, Qian Zeng, Siyuan Xia, Baotong Zhang, Zilong Wang, Xiaofei Wang, Hao Zheng","doi":"10.1016/j.chom.2024.09.013","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.013","url":null,"abstract":"Polyunsaturated fatty acids (PUFAs) are dietary components participating in neurotransmission and cell signaling. Pollen is a source of PUFAs for honeybees, and disruptions in dietary PUFAs reduce the cognitive performance of honeybees. We reveal that gut bacteria of honeybees contribute to fatty acid metabolism, impacting reward learning. Gut bacteria possess Δ-6 desaturases that mediate fatty acid elongation and compensate for the absence of honeybee factors required for fatty acid metabolism. Colonization with <em>Gilliamella apicola</em>, but not a mutant lacking the Δ-6 desaturase FADS2, increases the production of anandamide (AEA), a ligand of the endocannabinoid system, and alters learning and memory. AEA activates the Hymenoptera-specific transient receptor AmHsTRPA in astrocytes, which induces Ca<sup>2+</sup> influx and regulates glutamate re-uptake of glial cells to enhance reward learning. These findings illuminate the roles of gut symbionts in host fatty acid metabolism and the impacts of endocannabinoid signaling on the reward system of social insects.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"71 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439715","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}
Ishani Wickramage, Jeffrey VanWye, Klaas Max, John H. Lockhart, Ismet Hortu, Ezinne F. Mong, John Canfield, Hiran M. Lamabadu Warnakulasuriya Patabendige, Ozlem Guzeloglu-Kayisli, Kimiko Inoue, Atsuo Ogura, Charles J. Lockwood, Kemal M. Akat, Thomas Tuschl, Umit A. Kayisli, Hana Totary-Jain
{"title":"SINE RNA of the imprinted miRNA clusters mediates constitutive type III interferon expression and antiviral protection in hemochorial placentas","authors":"Ishani Wickramage, Jeffrey VanWye, Klaas Max, John H. Lockhart, Ismet Hortu, Ezinne F. Mong, John Canfield, Hiran M. Lamabadu Warnakulasuriya Patabendige, Ozlem Guzeloglu-Kayisli, Kimiko Inoue, Atsuo Ogura, Charles J. Lockwood, Kemal M. Akat, Thomas Tuschl, Umit A. Kayisli, Hana Totary-Jain","doi":"10.1016/j.chom.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.003","url":null,"abstract":"(Cell Host & Microbe <em>31</em>, 1185–1199.e1–e10; July 12, 2023)","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"2 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142415601","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":"Hospitalization throws the preterm gut microbiome off-key","authors":"Jing Qian, Emily N. Yeo, Matthew R. Olm","doi":"10.1016/j.chom.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.009","url":null,"abstract":"Environmental exposures substantially influence the infant gut microbiome. In this issue of <em>Cell Host & Microbe</em>, Thänert et al.<span><span><sup>1</sup></span></span> characterize how medical interventions in the neonatal intensive care unit (NICU) shape gut microbiome dynamics in the first months of life by analyzing over 2,500 fecal samples with metagenomics and metatranscriptomics.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"37 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385741","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":"Gut microbiome and bladder cancer: A new link through nitrosamine metabolism","authors":"Sridhar Mani","doi":"10.1016/j.chom.2024.09.003","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.003","url":null,"abstract":"A recent <em>Nature</em> paper<span><span><sup>1</sup></span></span> reveals that gut microbes metabolize N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) into the bladder carcinogen N-<em>n</em>-butyl-N-(3-carboxypropyl)-nitrosamine (BCPN) in the intestines, establishing a direct link between gut microbial activity and the development of bladder cancer.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"33 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385766","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}
George D. Moschonas, Louis Delhaye, Robin Cooreman, Franziska Hüsers, Anayat Bhat, Zoe Stylianidou, Elien De Bousser, Laure De Pryck, Hanna Grzesik, Delphine De Sutter, Eef Parthoens, Anne-Sophie De Smet, Aleksandra Maciejczuk, Saskia Lippens, Nico Callewaert, Linos Vandekerckhove, Zeger Debyser, Beate Sodeik, Sven Eyckerman, Xavier Saelens
{"title":"MX2 forms nucleoporin-comprising cytoplasmic biomolecular condensates that lure viral capsids","authors":"George D. Moschonas, Louis Delhaye, Robin Cooreman, Franziska Hüsers, Anayat Bhat, Zoe Stylianidou, Elien De Bousser, Laure De Pryck, Hanna Grzesik, Delphine De Sutter, Eef Parthoens, Anne-Sophie De Smet, Aleksandra Maciejczuk, Saskia Lippens, Nico Callewaert, Linos Vandekerckhove, Zeger Debyser, Beate Sodeik, Sven Eyckerman, Xavier Saelens","doi":"10.1016/j.chom.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.chom.2024.09.002","url":null,"abstract":"Human myxovirus resistance 2 (MX2) can restrict HIV-1 and herpesviruses at a post-entry step through a process requiring an interaction between MX2 and the viral capsids. The involvement of other host cell factors, however, remains poorly understood. Here, we mapped the proximity interactome of MX2, revealing strong enrichment of phenylalanine-glycine (FG)-rich proteins related to the nuclear pore complex as well as proteins that are part of cytoplasmic ribonucleoprotein granules. MX2 interacted with these proteins to form multiprotein cytoplasmic biomolecular condensates that were essential for its anti-HIV-1 and anti-herpes simplex virus 1 (HSV-1) activity. MX2 condensate formation required the disordered N-terminal region and MX2 dimerization. Incoming HIV-1 and HSV-1 capsids associated with MX2 at these dynamic cytoplasmic biomolecular condensates, preventing nuclear entry of their viral genomes. Thus, MX2 forms cytoplasmic condensates that likely act as nuclear pore decoys, trapping capsids and inducing premature viral genome release to interfere with nuclear targeting of HIV-1 and HSV-1.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"64 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385772","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":"RNAi, a sword of plant seeds to combat viral infections","authors":"Yan Wang, Yule Liu","doi":"10.1016/j.chom.2024.08.019","DOIUrl":"https://doi.org/10.1016/j.chom.2024.08.019","url":null,"abstract":"Vertical transmission of plant viruses through seeds has been known for a century, yet the mechanism for seeds to combat viral infection remains unclear. In this issue of <em>Cell Host & Microbe</em>, Liu and Ding demonstrate the genetic requirement of RNA silencing (RNAi) pathway for plants to suppress seed transmission.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"36 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385769","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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