Cell host & microbe最新文献_第5页

Rare twin cysteine residues in the HIV-1 envelope variable region 1 link to neutralization escape and breadth development

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-02-04 DOI: 10.1016/j.chom.2025.01.004

Maria C. Hesselman, Marius Zeeb, Peter Rusert, Chloé Pasin, Jennifer Mamrosh, Samuel Kariuki, Ian Pichler, Michèle Sickmann, Masako M. Kaufmann, Daniel Schmidt, Nikolas Friedrich, Karin J. Metzner, Audrey Rindler, Herbert Kuster, Craig Adams, Ruwayhida Thebus, Michael Huber, Sabine Yerly, Karoline Leuzinger, Matthieu Perreau, Alexandra Trkola

{"title":"Rare twin cysteine residues in the HIV-1 envelope variable region 1 link to neutralization escape and breadth development","authors":"Maria C. Hesselman, Marius Zeeb, Peter Rusert, Chloé Pasin, Jennifer Mamrosh, Samuel Kariuki, Ian Pichler, Michèle Sickmann, Masako M. Kaufmann, Daniel Schmidt, Nikolas Friedrich, Karin J. Metzner, Audrey Rindler, Herbert Kuster, Craig Adams, Ruwayhida Thebus, Michael Huber, Sabine Yerly, Karoline Leuzinger, Matthieu Perreau, Alexandra Trkola","doi":"10.1016/j.chom.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.004","url":null,"abstract":"Identifying HIV-1 envelope (Env) traits associated with neutralization cross-reactivity is crucial for vaccine design. Variable loops 1 and 2 (V1V2), positioned at the Env trimer apex, are key regions linked to neutralization. We describe non-canonical cysteine (Cys) residues in V1 that are enriched in individuals with elite neutralization breadth. Analyzing over 65,000 V1 sequences from the CATNAP database, AMP trials, and longitudinal HIV-1 cohorts (SHCS, ZPHI, and CAPRISA), we found that Env variants with extra V1 Cys are present at low levels and fluctuate over time. Extra V1 Cys associate with elite plasma neutralization, and two additional Cys are preferred, suggesting stabilization through disulfide bonds. Among 34 broadly neutralizing antibody (bnAb)-inducer Envs, 17.6% had elongated V1 regions with extra Cys. These extra Cys moderately increased neutralization resistance and altered bnAb epitope accessibility. Collectively, altering epitope exposure alongside Env stabilization renders the V1 twin Cys motif a promising feature for HIV-1 bnAb immunogens.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"19 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083565","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}

引用次数: 0

Competitive behaviors in Serratia marcescens are coordinately regulated by a lifestyle switch frequently inactivated in the clinical environment

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-01-29 DOI: 10.1016/j.chom.2025.01.001

David J. Williams, Alexandra Hawkins, Ruth E. Hernandez, Giuseppina Mariano, Katharine Mathers, Grant Buchanan, Barnaby J. Stonier, Teresa Inkster, Alistair Leanord, James D. Chalmers, Nicholas R. Thomson, Matthew T.G. Holden, Sarah J. Coulthurst

{"title":"Competitive behaviors in Serratia marcescens are coordinately regulated by a lifestyle switch frequently inactivated in the clinical environment","authors":"David J. Williams, Alexandra Hawkins, Ruth E. Hernandez, Giuseppina Mariano, Katharine Mathers, Grant Buchanan, Barnaby J. Stonier, Teresa Inkster, Alistair Leanord, James D. Chalmers, Nicholas R. Thomson, Matthew T.G. Holden, Sarah J. Coulthurst","doi":"10.1016/j.chom.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.chom.2025.01.001","url":null,"abstract":"Opportunistic bacterial pathogens must compete with other bacteria and switch between host- and environment-adapted states. Type VI secretion systems (T6SSs) occur widely in gram-negative bacteria and can efficiently kill neighboring competitors. We determined the distribution of T6SSs across the genus Serratia and observed that a highly conserved antibacterial T6SS is differentially active between closely related clinical isolates of Serratia marcescens. By combining genomic and experimental approaches, we identified a genus-core two-component system, BetR-Reg1-Reg2, that controls T6SS activity and exhibits frequent inactivating mutations, exclusively in S. marcescens isolates of clinical origin. This regulatory system controls a number of lifestyle-related traits at transcriptional and post-translational levels, including T6SS activity, antibiotic production, motility, and adhesion, with loss of BetR increasing virulence in an in vivo infection model. Our data support a model whereby this system represents a conserved, modular switch from sessile to pioneering and aggressive behavior, which is subject to selection pressure in clinical environments.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"32 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055385","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}

引用次数: 0

Fiber- and acetate-mediated modulation of MHC-II expression on intestinal epithelium protects from Clostridioides difficile infection 纤维和醋酸盐介导的肠上皮MHC-II表达调节可保护肠上皮免受艰难梭菌感染

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-01-17 DOI: 10.1016/j.chom.2024.12.017

José L. Fachi, Sarah de Oliveira, Tihana Trsan, Silvia Penati, Susan Gilfillan, Siyan Cao, Pollyana Ribeiro Castro, Mariane Font Fernandes, Krzysztof L. Hyrc, Xiuli Liu, Patrick Fernandes Rodrigues, Bishan Bhattarai, Brian T. Layden, Marco Aurélio R. Vinolo, Marco Colonna

{"title":"Fiber- and acetate-mediated modulation of MHC-II expression on intestinal epithelium protects from Clostridioides difficile infection","authors":"José L. Fachi, Sarah de Oliveira, Tihana Trsan, Silvia Penati, Susan Gilfillan, Siyan Cao, Pollyana Ribeiro Castro, Mariane Font Fernandes, Krzysztof L. Hyrc, Xiuli Liu, Patrick Fernandes Rodrigues, Bishan Bhattarai, Brian T. Layden, Marco Aurélio R. Vinolo, Marco Colonna","doi":"10.1016/j.chom.2024.12.017","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.017","url":null,"abstract":"Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune cell interactions in regulating susceptibility to Clostridioides difficile infection (CDI). We find that a low-fiber diet increases MHC-II expression in the colonic epithelium, which, in turn, worsens CDI by promoting the development of pathogenic CD4+ intraepithelial lymphocytes (IELs). The influence of dietary fibers on MHC-II expression is mediated by its metabolic product, acetate, and its receptor, free fatty acid receptor 2 (FFAR2). While acetate activation of FFAR2 on epithelial cells helps resist CDI, it does not directly regulate MHC-II expression. Instead, MHC-II is regulated by FFAR2 in type 3 innate lymphoid cells (ILC3s). Acetate enhances interleukin-22 (IL-22) production by ILC3s, which then suppresses MHC-II expression on the colonic epithelium. In conclusion, a low-fiber diet reduces acetate-induced IL-22 production by ILC3s, leading to increased MHC-II on the colonic epithelium. This change affects recovery from CDI by expanding the population of pathogenic CD4+ IELs.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"95 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987461","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}

引用次数: 0

Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning 通过大规模结合实验和机器学习解码丝状病毒受体结合的蓝图

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-01-15 DOI: 10.1016/j.chom.2024.12.016

Gorka Lasso, Michael Grodus, Estefania Valencia, Veronica DeJesus, Eliza Liang, Isabel Delwel, Rob H. Bortz, Dmitry Lupyan, Hanna Y. Ehrlich, Adrian A. Castellanos, Andrea Gazzo, Heather L. Wells, Supaporn Wacharapluesadee, Alexandre Tremeau-Bravard, Janine F.R. Seetahal, Tom Hughes, Jimmy Lee, Mei-Ho Lee, Anna R. Sjodin, Marike Geldenhuys, Simon J. Anthony

{"title":"Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning","authors":"Gorka Lasso, Michael Grodus, Estefania Valencia, Veronica DeJesus, Eliza Liang, Isabel Delwel, Rob H. Bortz, Dmitry Lupyan, Hanna Y. Ehrlich, Adrian A. Castellanos, Andrea Gazzo, Heather L. Wells, Supaporn Wacharapluesadee, Alexandre Tremeau-Bravard, Janine F.R. Seetahal, Tom Hughes, Jimmy Lee, Mei-Ho Lee, Anna R. Sjodin, Marike Geldenhuys, Simon J. Anthony","doi":"10.1016/j.chom.2024.12.016","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.016","url":null,"abstract":"Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species. We found that GP-NPC1 binding correlated poorly with phylogeny. By integrating binding assays with machine learning, we identified genetic factors influencing virus-receptor-binding and predicted GP-NPC1-binding avidity for additional filoviruses and bats. Moreover, combining receptor-binding avidities with bat geographic distribution and the locations of previous Ebola outbreaks allowed us to rank bats by their potential as Ebola virus hosts. This study represents a comprehensive investigation of filovirus-receptor binding in bats (1,484 GP-NPC1 pairs, 11 filoviruses, and 135 bats) and describes a multidisciplinary approach to predict susceptible species and guide filovirus host surveillance.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"28 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981358","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}

引用次数: 0

MFSD6 is an entry receptor for respiratory enterovirus D68 MFSD6是呼吸道肠道病毒D68的一种进入受体

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-01-10 DOI: 10.1016/j.chom.2024.12.015

Xize Liu, Huili Li, Zhaoxue Li, Delong Gao, Junfeng Zhou, Fushun Ni, Qing Yu, Yuehan Huang, Yubin Tang, Ling Xue, Shijin Wang, Jiaxin Yang, Haoran Guo, Yonggang Wang, Xiao-Fang Yu, Zhenglei Yu, Wei Wei

{"title":"MFSD6 is an entry receptor for respiratory enterovirus D68","authors":"Xize Liu, Huili Li, Zhaoxue Li, Delong Gao, Junfeng Zhou, Fushun Ni, Qing Yu, Yuehan Huang, Yubin Tang, Ling Xue, Shijin Wang, Jiaxin Yang, Haoran Guo, Yonggang Wang, Xiao-Fang Yu, Zhenglei Yu, Wei Wei","doi":"10.1016/j.chom.2024.12.015","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.015","url":null,"abstract":"Enterovirus D68 (EV-D68) is a leading non-polio enterovirus that causes severe respiratory diseases and poliomyelitis-like illness in children. Viral entry represents a potential multifaceted target for antiviral intervention; however, there are no approved inhibitors to block EV-D68. Here, we identify the functionally undescribed membrane protein major facilitator superfamily-domain-containing protein 6 (MFSD6) as an EV-D68 entry factor amenable to therapeutic intervention. Specifically, MFSD6 expression is crucial for EV-D68 replication. MFSD6 binds to EV-D68 particles and is necessary for virus attachment to cells. The second extracellular domain of the MFSD6 molecule is involved in the recognition of EV-D68. On the basis of these findings, we engineered a recombinant protein complex comprising the MFSD6 ectodomain fused to Fc (MFSD6-Fc(CH3)), which potently inhibited EV-D68 uptake. MFSD6-Fc(CH3) effectively blocked EV-D68 infection in vitro and prevented lethality in newborn mice. In conclusion, our study not only identifies MFSD6 as an EV-D68 entry factor but also reveals a potential antiviral target and therapeutic agent.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"28 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939629","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}

引用次数: 0

Exploring the open (host) range 探索开放（主机）范围

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-01-08 DOI: 10.1016/j.chom.2024.12.014

David A. Baltrus, Brian H. Kvitko

引用次数: 0

The intestinal fungus Aspergillus tubingensis promotes polycystic ovary syndrome through a secondary metabolite 肠道真菌塔宾曲霉通过次级代谢物促进多囊卵巢综合征

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-01-08 DOI: 10.1016/j.chom.2024.12.006

Jiayu Wu, Kai Wang, Xinyu Qi, Shuang Zhou, Shuyun Zhao, Meisong Lu, Qixing Nie, Meng Li, Mengwei Han, Xi Luo, Chuyu Yun, Pengcheng Wang, Rong Li, Chao Zhong, Xiaofei Yu, Wen-bing Yin, Changtao Jiang, Jie Qiao, Yanli Pang

{"title":"The intestinal fungus Aspergillus tubingensis promotes polycystic ovary syndrome through a secondary metabolite","authors":"Jiayu Wu, Kai Wang, Xinyu Qi, Shuang Zhou, Shuyun Zhao, Meisong Lu, Qixing Nie, Meng Li, Mengwei Han, Xi Luo, Chuyu Yun, Pengcheng Wang, Rong Li, Chao Zhong, Xiaofei Yu, Wen-bing Yin, Changtao Jiang, Jie Qiao, Yanli Pang","doi":"10.1016/j.chom.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.chom.2024.12.006","url":null,"abstract":"Polycystic ovary syndrome (PCOS) affects 6%–10% of women of reproductive age and is known to be associated with disruptions in the gut bacteria. However, the role of the gut mycobiota in PCOS pathology remains unclear. Using culture-dependent and internal transcribed spacer 2 (ITS2)-sequencing methods, we discovered an enrichment of the gut-colonizable fungus Aspergillus tubingensis in 226 individuals, with or without PCOS, from 3 different geographical areas within China. Colonization of mice with A. tubingensis led to a PCOS-like phenotype due to inhibition of Aryl hydrocarbon receptor (AhR) signaling and reduced interleukin (IL)-22 secretion in intestinal group 3 innate lymphoid cells (ILC3s). By developing a strain-diversity-based-activity metabolite screening workflow, we identified secondary metabolite AT-C1 as an endogenous AhR antagonist and a key mediator of PCOS. Our findings demonstrate that an intestinal fungus and its secondary metabolite play a critical role in PCOS pathogenesis, offering a therapeutic strategy for improving the management of the disease.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"35 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936084","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}

引用次数: 0

Fungal influence: The role of the gut mycobiome in women’s health 真菌的影响：肠道菌群在女性健康中的作用

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-01-08 DOI: 10.1016/j.chom.2024.12.005

Tian-Yi Zhang, Ning-Ning Liu

引用次数: 0

Commensal fungi, a force to be reckoned with 共生真菌，一股不可忽视的力量

IF 30.3 1区医学

Cell host & microbe Pub Date : 2025-01-08 DOI: 10.1016/j.chom.2024.12.012

Dingjiacheng Jia, Shujie Chen

引用次数: 0

The butterfly effect of the strain richness influences the efficacy of microbiota transplantation 菌株丰富度的蝴蝶效应影响菌群移植的效果