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JOURNAL ARTICLE
Pengcheng Shang, Rita Dos Santos Natividade, Gwen M Taylor, Ankita Ray, Olivia L Welsh, Kay L Fiske, Danica M Sutherland, David Alsteens, Terence S Dermody
Mammalian orthoreovirus (reovirus) is a nonenveloped virus that establishes primary infection in the intestine and disseminates to sites of secondary infection, including the CNS. Reovirus entry involves multiple engagement factors, but how the virus disseminates systemically and targets neurons remains unclear. In this study, we identified murine neuropilin 1 (mNRP1) as a receptor for reovirus. mNRP1 binds reovirus with nanomolar affinity using a unique mechanism of virus-receptor interaction, which is coordinated by multiple interactions between distinct reovirus capsid subunits and multiple NRP1 extracellular domains...
May 8, 2024: Cell Host & Microbe
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JOURNAL ARTICLE
Kevin Wiehe, Kevin O Saunders, Victoria Stalls, Derek W Cain, Sravani Venkatayogi, Joshua S Martin Beem, Madison Berry, Tyler Evangelous, Rory Henderson, Bhavna Hora, Shi-Mao Xia, Chuancang Jiang, Amanda Newman, Cindy Bowman, Xiaozhi Lu, Mary E Bryan, Joena Bal, Aja Sanzone, Haiyan Chen, Amanda Eaton, Mark A Tomai, Christopher B Fox, Ying K Tam, Christopher Barbosa, Mattia Bonsignori, Hiromi Muramatsu, S Munir Alam, David C Montefiori, Wilton B Williams, Norbert Pardi, Ming Tian, Drew Weissman, Frederick W Alt, Priyamvada Acharya, Barton F Haynes
A major goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs). Although success has been achieved in initiating bnAb B cell lineages, design of boosting immunogens that select for bnAb B cell receptors with improbable mutations required for bnAb affinity maturation remains difficult. Here, we demonstrate a process for designing boosting immunogens for a V3-glycan bnAb B cell lineage. The immunogens induced affinity-matured antibodies by selecting for functional improbable mutations in bnAb precursor knockin mice...
April 22, 2024: Cell Host & Microbe
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JOURNAL ARTICLE
Ting-Ting Li, Xi Chen, Da Huo, Mohammad Arifuzzaman, Shanshan Qiao, Wen-Bing Jin, Huiqing Shi, Xin V Li, Iliyan D Iliev, David Artis, Chun-Jun Guo
The intestine and liver are thought to metabolize dietary nutrients and regulate host nutrient homeostasis. Here, we find that the gut microbiota also reshapes the host amino acid (aa) landscape via efficiently metabolizing intestinal aa. To identify the responsible microbes/genes, we developed a metabolomics-based assay to screen 104 commensals and identified candidates that efficiently utilize aa. Using genetics, we identified multiple responsible metabolic genes in phylogenetically diverse microbes. By colonizing germ-free mice with the wild-type strain and their isogenic mutant deficient in individual aa-metabolizing genes, we found that these genes regulate the availability of gut and circulatory aa...
April 22, 2024: Cell Host & Microbe
#4
JOURNAL ARTICLE
Assessing phage-host population dynamics by reintroducing virulent viruses to synthetic microbiomes.
Jacob Wilde, Randy Boyes, Avery V Robinson, Brendan A Daisley, Alexander J Botschner, Dylan J L Brettingham, Christine V Macpherson, Elizabeth Mallory, Emma Allen-Vercoe
Microbiomes feature complex interactions between diverse bacteria and bacteriophages. Synthetic microbiomes offer a powerful way to study these interactions; however, a major challenge is obtaining a representative bacteriophage population during the bacterial isolation process. We demonstrate that colony isolation reliably excludes virulent viruses from sample sources with low virion-to-bacteria ratios such as feces, creating "virulent virus-free" controls. When the virulent dsDNA virome is reintroduced to a 73-strain synthetic gut microbiome in a bioreactor model of the human colon, virulent viruses target susceptible strains without significantly altering community structure or metabolism...
April 18, 2024: Cell Host & Microbe
#5
JOURNAL ARTICLE
Yi He, Xiujuan Yang, Xiaobo Xia, Yuhua Wang, Yifan Dong, Lei Wu, Peng Jiang, Xu Zhang, Cong Jiang, Hongxiang Ma, Wujun Ma, Cong Liu, Ryan Whitford, Matthew R Tucker, Zhengguang Zhang, Gang Li
Fusarium head blight (FHB) is a devastating wheat disease. Fhb1, the most widely applied genetic locus for FHB resistance, is conferred by TaHRC of an unknown mode of action. Here, we show that TaHRC alleles distinctly drive liquid-liquid phase separation (LLPS) within a proteinaceous complex, determining FHB susceptibility or resistance. TaHRC-S (susceptible) exhibits stronger LLPS ability than TaHRC-R (resistant), and this distinction is further intensified by fungal mycotoxin deoxynivalenol, leading to opposing FHB symptoms...
April 16, 2024: Cell Host & Microbe
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JOURNAL ARTICLE
Qi Su, Raphaela I Lau, Qin Liu, Moses K T Li, Joyce Wing Yan Mak, Wenqi Lu, Ivan S F Lau, Louis H S Lau, Giann T Y Yeung, Chun Pan Cheung, Whitney Tang, Chengyu Liu, Jessica Y L Ching, Pui Kuan Cheong, Francis K L Chan, Siew C Ng
The mechanisms underlying the many phenotypic manifestations of post-acute COVID-19 syndrome (PACS) are poorly understood. Herein, we characterized the gut microbiome in heterogeneous cohorts of subjects with PACS and developed a multi-label machine learning model for using the microbiome to predict specific symptoms. Our processed data covered 585 bacterial species and 500 microbial pathways, explaining 12.7% of the inter-individual variability in PACS. Three gut-microbiome-based enterotypes were identified in subjects with PACS and associated with different phenotypic manifestations...
April 16, 2024: Cell Host & Microbe
#7
JOURNAL ARTICLE
Miro Thorsten Wilhelm Plum, Hoi Ching Cheung, Patricia Reist Iscar, Yahua Chen, Yunn-Hwen Gan, Marek Basler
To spread within a host, intracellular Burkholderia form actin tails to generate membrane protrusions into neighboring host cells and use type VI secretion system-5 (T6SS-5) to induce cell-cell fusions. Here, we show that B. thailandensis also uses T6SS-5 to lyse protrusions to directly spread from cell to cell. Dynamin-2 recruitment to the membrane near a bacterium was followed by a short burst of T6SS-5 activity. This resulted in the polymerization of the actin of the newly invaded host cell and disruption of the protrusion membrane...
April 16, 2024: Cell Host & Microbe
#8
JOURNAL ARTICLE
Sang-Hoon Sin, Anthony B Eason, Yongbaek Kim, Johann W Schneider, Blossom Damania, Dirk P Dittmer
Kaposi sarcoma (KS) is the most common cancer in persons living with HIV. It is caused by KS-associated herpesvirus (KSHV). There exists no animal model for KS. Pronuclear injection of the 170,000-bp viral genome induces early-onset, aggressive angiosarcoma in transgenic mice. The tumors are histopathologically indistinguishable from human KS. As in human KS, all tumor cells express the viral latency-associated nuclear antigen (LANA). The tumors transcribe most viral genes, whereas endothelial cells in other organs only transcribe the viral latent genes...
April 15, 2024: Cell Host & Microbe
#9
JOURNAL ARTICLE
Marcel Sprenger, Malte Siemers, Sebastian Krautwurst, Kai Papenfort
Many, if not all, bacteria use quorum sensing (QS) to control collective behaviors, and more recently, QS has also been discovered in bacteriophages (phages). Phages can produce communication molecules of their own, or "listen in" on the host's communication processes, to switch between lytic and lysogenic modes of infection. Here, we study the interaction of Vibrio cholerae with the lysogenic phage VP882, which is activated by the QS molecule DPO. We discover that induction of VP882 results in the binding of phage transcripts to the major RNA chaperone Hfq, which in turn outcompetes and downregulates host-encoded small RNAs (sRNAs)...
April 2, 2024: Cell Host & Microbe
#10
JOURNAL ARTICLE
Joshua M Kirsch, Andrew J Hryckowian, Breck A Duerkop
Insertion sequence (IS) elements are mobile genetic elements in bacterial genomes that support adaptation. We developed a database of IS elements coupled to a computational pipeline that identifies IS element insertions in the microbiota. We discovered that diverse IS elements insert into the genomes of intestinal bacteria regardless of human host lifestyle. These insertions target bacterial accessory genes that aid in their adaptation to unique environmental conditions. Using IS expansion in Bacteroides, we show that IS activity leads to the insertion of "hot spots" in accessory genes...
March 21, 2024: Cell Host & Microbe
#11
JOURNAL ARTICLE
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, Yuxin Mao, Kristin L Patrick, Robert O Watson, William K Russell, Aiying Yu, Jieqiang Zhong, Fengguang Guo, Mingqian Li, Mingyuan Zhou, Xiaoning Qian, Koichi S Kobayashi, Jianxun Song, Suresh Panthee, Yehia Mechref, Thomas A Ficht, Qing-Ming Qin, Paul de Figueiredo
Many powerful methods have been employed to elucidate the global transcriptomic, proteomic, or metabolic responses to pathogen-infected host cells. However, the host glycome responses to bacterial infection remain largely unexplored, and hence, our understanding of the molecular mechanisms by which bacterial pathogens manipulate the host glycome to favor infection remains incomplete. Here, we address this gap by performing a systematic analysis of the host glycome during infection by the bacterial pathogen Brucella spp...
March 20, 2024: Cell Host & Microbe
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JOURNAL ARTICLE
Xiaoqiang Zhu, Xiaowen Huang, Muni Hu, Rongrong Sun, Jiantao Li, Hai Wang, Xuefeng Pan, Yanru Ma, Lijun Ning, Tianying Tong, Yilu Zhou, Jinmei Ding, Ying Zhao, Baoqin Xuan, Jing-Yuan Fang, Jie Hong, Jason Wing Hon Wong, Youwei Zhang, Haoyan Chen
Immunotherapy has revolutionized cancer treatment, but inconsistent responses persist. Our study delves into the intriguing phenomenon of enhanced immunotherapy sensitivity in older individuals with cancers. Through a meta-analysis encompassing 25 small-to-mid-sized trials of immune checkpoint blockade (ICB), we demonstrate that older individuals exhibit heightened responsiveness to ICB therapy. To understand the underlying mechanism, we reanalyze single-cell RNA sequencing (scRNA-seq) data from multiple studies and unveil distinct upregulation of exhausted and cytotoxic T cell markers within the tumor microenvironment (TME) of older patients...
March 18, 2024: Cell Host & Microbe
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JOURNAL ARTICLE
Gabriel Vasconcelos Pereira, Marie Boudaud, Mathis Wolter, Celeste Alexander, Alessandro De Sciscio, Erica T Grant, Bruno Caetano Trindade, Nicholas A Pudlo, Shaleni Singh, Austin Campbell, Mengrou Shan, Li Zhang, Qinnan Yang, Stéphanie Willieme, Kwi Kim, Trisha Denike-Duval, Jaime Fuentes, André Bleich, Thomas M Schmidt, Lucy Kennedy, Costas A Lyssiotis, Grace Y Chen, Kathryn A Eaton, Mahesh S Desai, Eric C Martens
Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, interleukin-10, we show that a fiber-deprived gut microbiota promotes the deterioration of colonic mucus, leading to lethal colitis. Inflammation starts with the expansion of natural killer cells and altered immunoglobulin-A coating of some bacteria...
March 18, 2024: Cell Host & Microbe
#14
JOURNAL ARTICLE
Qiaochu Shen, Keiichi Hasegawa, Nicole Oelerich, Anna Prakken, Lea Weiler Tersch, Junli Wang, Frowin Reichhardt, Alexandra Tersch, Je Cuan Choo, Ton Timmers, Kay Hofmann, Jane E Parker, Jijie Chai, Takaki Maekawa
The plant homolog of vertebrate necroptosis inducer mixed-lineage kinase domain-like (MLKL) contributes to downstream steps in Toll-interleukin-1 receptor domain NLR (TNL)-receptor-triggered immunity. Here, we show that Arabidopsis MLKL1 (AtMLKL1) clusters into puncta at the plasma membrane upon TNL activation and that this sub-cellular reorganization is dependent on the TNL signal transducer, EDS1. We find that AtMLKLs confer TNL-triggered immunity in parallel with RPW8-type HeLo-domain-containing NLRs (RNLs) and that the AtMLKL N-terminal HeLo domain is indispensable for both immunity and clustering...
March 13, 2024: Cell Host & Microbe
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JOURNAL ARTICLE
Xin Zhou, Xiaotao Shen, Jethro S Johnson, Daniel J Spakowicz, Melissa Agnello, Wenyu Zhou, Monica Avina, Alexander Honkala, Faye Chleilat, Shirley Jingyi Chen, Kexin Cha, Shana Leopold, Chenchen Zhu, Lei Chen, Lin Lyu, Daniel Hornburg, Si Wu, Xinyue Zhang, Chao Jiang, Liuyiqi Jiang, Lihua Jiang, Ruiqi Jian, Andrew W Brooks, Meng Wang, Kévin Contrepois, Peng Gao, Sophia Miryam Schüssler-Fiorenza Rose, Thi Dong Binh Tran, Hoan Nguyen, Alessandra Celli, Bo-Young Hong, Eddy J Bautista, Yair Dorsett, Paula B Kavathas, Yanjiao Zhou, Erica Sodergren, George M Weinstock, Michael P Snyder
To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment...
March 8, 2024: Cell Host & Microbe
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JOURNAL ARTICLE
William M de Souza, Marcilio J Fumagalli, Shirlene T S de Lima, Pierina L Parise, Deyse C M Carvalho, Cristian Hernandez, Ronaldo de Jesus, Jeany Delafiori, Darlan S Candido, Victor C Carregari, Stefanie P Muraro, Gabriela F Souza, Leda M Simões Mello, Ingra M Claro, Yamilka Díaz, Rodrigo B Kato, Lucas N Trentin, Clauber H S Costa, Ana Carolina B M Maximo, Karene F Cavalcante, Tayna S Fiuza, Vânia A F Viana, Maria Elisabeth L Melo, Clarissa P M Ferraz, Débora B Silva, Larissa M F Duarte, Priscilla P Barbosa, Mariene R Amorim, Carla C Judice, Daniel A Toledo-Teixeira, Mariana S Ramundo, Patricia V Aguilar, Emerson L L Araújo, Fabio T M Costa, Thiago Cerqueira-Silva, Ricardo Khouri, Viviane S Boaventura, Luiz Tadeu M Figueiredo, Rong Fang, Brechla Moreno, Sandra López-Vergès, Liana Perdigão Mello, Munir S Skaf, Rodrigo R Catharino, Fabiana Granja, Daniel Martins-de-Souza, Jessica A Plante, Kenneth S Plante, Ester C Sabino, Michael S Diamond, Eliseo Eugenin, José Luiz Proença-Módena, Nuno R Faria, Scott C Weaver
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors...
March 8, 2024: Cell Host & Microbe
#17
JOURNAL ARTICLE
Eliza P-I Loo, Paloma Durán, Tin Yau Pang, Philipp Westhoff, Chen Deng, Carlos Durán, Martin Lercher, Ruben Garrido-Oter, Wolf B Frommer
Plant roots are functionally heterogeneous in cellular architecture, transcriptome profile, metabolic state, and microbial immunity. We hypothesized that axial differentiation may also impact spatial colonization by root microbiota along the root axis. We developed two growth systems, ArtSoil and CD-Rhizotron, to grow and then dissect Arabidopsis thaliana roots into three segments. We demonstrate that distinct endospheric and rhizosphere bacterial communities colonize the segments, supporting the hypothesis of microbiota differentiation along the axis...
March 8, 2024: Cell Host & Microbe
#18
JOURNAL ARTICLE
Madeline Krieger, Yasser M AbdelRahman, Dongseok Choi, Elizabeth A Palmer, Anna Yoo, Sean McGuire, Jens Kreth, Justin Merritt
The ubiquitous inflammophilic oral pathobiont Fusobacterium nucleatum (Fn) is widely recognized for its strong association with inflammatory dysbiotic diseases and cancer. Fn is subdivided into four subspecies, which are historically considered functionally interchangeable in the oral cavity. To test this assumption, we analyzed patient-matched dental plaque and odontogenic abscess clinical specimens and examined whether an inflammatory environment selects for/against particular Fn subspecies. Dental plaque harbored a greater diversity of fusobacteria, with Fn...
March 8, 2024: Cell Host & Microbe
#19
JOURNAL ARTICLE
Hanqi Li, Alice Fletcher-Etherington, Leah M Hunter, Swati Keshri, Ceri A Fielding, Katie Nightingale, Benjamin Ravenhill, Luis Nobre, Martin Potts, Robin Antrobus, Colin M Crump, David C Rubinsztein, Richard J Stanton, Michael P Weekes
Human cytomegalovirus (HCMV) is an important human pathogen that regulates host immunity and hijacks host compartments, including lysosomes, to assemble virions. We combined a quantitative proteomic analysis of HCMV infection with a database of proteins involved in vacuolar acidification, revealing Dmx-like protein-1 (DMXL1) as the only protein that acidifies vacuoles yet is degraded by HCMV. Systematic comparison of viral deletion mutants reveals the uncharacterized 7 kDa US33A protein as necessary and sufficient for DMXL1 degradation, which occurs via recruitment of the E3 ubiquitin ligase Kip1 ubiquitination-promoting complex (KPC)...
March 5, 2024: Cell Host & Microbe
#20
JOURNAL ARTICLE
Xue Liu, Laurye Van Maele, Laura Matarazzo, Daphnée Soulard, Vinicius Alves Duarte da Silva, Vincent de Bakker, Julien Dénéréaz, Florian P Bock, Michael Taschner, Jinzhao Ou, Stephan Gruber, Victor Nizet, Jean-Claude Sirard, Jan-Willem Veening
Several vaccines targeting bacterial pathogens show reduced efficacy upon concurrent viral infection, indicating that a new vaccinology approach is required. To identify antigens for the human pathogen Streptococcus pneumoniae that are effective following influenza infection, we performed CRISPRi-seq in a murine model of superinfection and identified the conserved lafB gene as crucial for virulence. We show that LafB is a membrane-associated, intracellular protein that catalyzes the formation of galactosyl-glucosyl-diacylglycerol, a glycolipid important for cell wall homeostasis...
February 21, 2024: Cell Host & Microbe
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