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
Yi Wu, Sofya K Garushyants, Anne van den Hurk, Cristian Aparicio-Maldonado, Simran Krishnakant Kushwaha, Claire M King, Yaqing Ou, Thomas C Todeschini, Martha R J Clokie, Andrew D Millard, Yilmaz Emre Gençay, Eugene V Koonin, Franklin L Nobrega
Bacterial defense against phage predation involves diverse defense systems acting individually and concurrently, yet their interactions remain poorly understood. We investigated >100 defense systems in 42,925 bacterial genomes and identified numerous instances of their non-random co-occurrence and negative association. For several pairs of defense systems significantly co-occurring in Escherichia coli strains, we demonstrate synergistic anti-phage activity. Notably, Zorya II synergizes with Druantia III and ietAS defense systems, while tmn exhibits synergy with co-occurring systems Gabija, Septu I, and PrrC...
February 19, 2024: Cell Host & Microbe
Ying-Xi Xu, Lu-Di Liu, Jiang-Yuan Zhu, Shan-Shan Zhu, Bing-Qi Ye, Jia-Lu Yang, Jing-Yi Huang, Zhi-Hao Huang, Yi You, Wen-Kang Li, Jia-Lin He, Min Xia, Yan Liu
Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A...
February 16, 2024: Cell Host & Microbe
Qiyi Chen, Chunyan Wu, Jinfeng Xu, Chen Ye, Xiang Chen, Hongliang Tian, Naixin Zong, Shaoyi Zhang, Long Li, Yuan Gao, Di Zhao, Xiaoqiong Lv, Qilin Yang, Le Wang, Jiaqu Cui, Zhiliang Lin, Jubao Lu, Rong Yang, Fang Yin, Nan Qin, Ning Li, Qian Xu, Huanlong Qin
Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906)...
February 12, 2024: Cell Host & Microbe
Qian Wang, Yicheng Guo, Anthony Bowen, Ian A Mellis, Riccardo Valdez, Carmen Gherasim, Aubree Gordon, Lihong Liu, David D Ho
COVID-19 vaccines have recently been updated to specifically encode or contain the spike protein of the SARS-CoV-2 XBB.1.5 subvariant, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report that administration of an updated monovalent mRNA vaccine booster (XBB.1.5 MV) to previously uninfected individuals boosted serum virus-neutralizing antibodies significantly against not only XBB.1.5 (27.0-fold increase) and EG...
February 10, 2024: Cell Host & Microbe
Marinelle Rodrigues, Parastoo Sabaeifard, Muhammed Sadik Yildiz, Adam Lyon, Laura Coughlin, Sara Ahmed, Nicole Poulides, Ahmet C Toprak, Cassie Behrendt, Xiaoyu Wang, Marguerite Monogue, Jiwoong Kim, Shuheng Gan, Xiaowei Zhan, Laura Filkins, Noelle S Williams, Lora V Hooper, Andrew Y Koh, Erdal Toprak
Antibiotic resistance and evasion are incompletely understood and complicated by the fact that murine interval dosing models do not fully recapitulate antibiotic pharmacokinetics in humans. To better understand how gastrointestinal bacteria respond to antibiotics, we colonized germ-free mice with a pan-susceptible genetically barcoded Escherichia coli clinical isolate and administered the antibiotic cefepime via programmable subcutaneous pumps, allowing closer emulation of human parenteral antibiotic dynamics...
February 6, 2024: Cell Host & Microbe
Fan Qi, Jianwei Li, Yingfei Ai, Keke Shangguan, Ping Li, Fucheng Lin, Yan Liang
In plant immunity, phosphatidic acid (PA) regulates reactive oxygen species (ROS) by binding to respiratory burst oxidase homolog D (RBOHD), an NADPH oxidase responsible for ROS production. Here, we analyze the influence of PA binding on RBOHD activity and the mechanism of RBOHD-bound PA generation. PA binding enhances RBOHD protein stability by inhibiting vacuolar degradation, thereby increasing chitin-induced ROS production. Mutations in diacylglycerol kinase 5 (DGK5), which phosphorylates diacylglycerol to produce PA, impair chitin-induced PA and ROS production...
February 2, 2024: Cell Host & Microbe
Andrew J Thompson, Nicholas C Wu, Angeles Canales, Chika Kikuchi, Xueyong Zhu, Beatriz Fernández de Toro, Francisco J Cañada, Charli Worth, Shengyang Wang, Ryan McBride, Wenjie Peng, Corwin M Nycholat, Jesús Jiménez-Barbero, Ian A Wilson, James C Paulson
Hemagglutinins (HAs) from human influenza viruses descend from avian progenitors that bind α2-3-linked sialosides and must adapt to glycans with α2-6-linked sialic acids on human airway cells to transmit within the human population. Since their introduction during the 1968 pandemic, H3N2 viruses have evolved over the past five decades to preferentially recognize human α2-6-sialoside receptors that are elongated through addition of poly-LacNAc. We show that more recent H3N2 viruses now make increasingly complex interactions with elongated receptors while continuously selecting for strains maintaining this phenotype...
January 29, 2024: Cell Host & Microbe
Mylène Perreault, Jillian Means, Erik Gerson, Michael James, Sean Cotton, Christopher G Bergeron, Mark Simon, Dylan Alexander Carlin, Nathan Schmidt, Theodore C Moore, Julie Blasbalg, Neal Sondheimer, Kenneth Ndugga-Kabuye, William S Denney, Vincent M Isabella, David Lubkowicz, Aoife Brennan, David L Hava
Methionine is an essential proteinogenic amino acid, but its excess can lead to deleterious effects. Inborn errors of methionine metabolism resulting from loss of function in cystathionine β-synthase (CBS) cause classic homocystinuria (HCU), which is managed by a methionine-restricted diet. Synthetic biotics are gastrointestinal tract-targeted live biotherapeutics that can be engineered to replicate the benefits of dietary restriction. In this study, we assess whether SYNB1353, an E. coli Nissle 1917 derivative, impacts circulating methionine and homocysteine levels in animals and healthy volunteers...
January 25, 2024: Cell Host & Microbe
Ju-Sim Kim, Lin Liu, Sashi Kant, David J Orlicky, Siva Uppalapati, Alyssa Margolis, Bennett J Davenport, Thomas E Morrison, Jennifer Matsuda, Michael McClelland, Jessica Jones-Carson, Andres Vazquez-Torres
Intracellular Salmonella experiencing oxidative stress downregulates aerobic respiration. To maintain cellular energetics during periods of oxidative stress, intracellular Salmonella must utilize terminal electron acceptors of lower energetic value than molecular oxygen. We show here that intracellular Salmonella undergoes anaerobic respiration during adaptation to the respiratory burst of the phagocyte NADPH oxidase in macrophages and in mice. Reactive oxygen species generated by phagocytes oxidize methionine, generating methionine sulfoxide...
January 24, 2024: Cell Host & Microbe
Vu L Ngo, Carolin M Lieber, Hae-Ji Kang, Kaori Sakamoto, Michal Kuczma, Richard K Plemper, Andrew T Gewirtz
Susceptibility to respiratory virus infections (RVIs) varies widely across individuals. Because the gut microbiome impacts immune function, we investigated the influence of intestinal microbiota composition on RVI and determined that segmented filamentous bacteria (SFB), naturally acquired or exogenously administered, protected mice against influenza virus (IAV) infection. Such protection, which also applied to respiratory syncytial virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was independent of interferon and adaptive immunity but required basally resident alveolar macrophages (AMs)...
January 23, 2024: Cell Host & Microbe
Tomokazu Tamura, Keita Mizuma, Hesham Nasser, Sayaka Deguchi, Miguel Padilla-Blanco, Yoshitaka Oda, Keiya Uriu, Jarel E M Tolentino, Shuhei Tsujino, Rigel Suzuki, Isshu Kojima, Naganori Nao, Ryo Shimizu, Lei Wang, Masumi Tsuda, Michael Jonathan, Yusuke Kosugi, Ziyi Guo, Alfredo A Hinay, Olivia Putri, Yoonjin Kim, Yuri L Tanaka, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, Akatsuki Saito, Jumpei Ito, Takashi Irie, Shinya Tanaka, Jiri Zahradnik, Terumasa Ikeda, Kazuo Takayama, Keita Matsuno, Takasuke Fukuhara, Kei Sato
In late 2023, several SARS-CoV-2 XBB descendants, notably EG.5.1, were predominant worldwide. However, a distinct SARS-CoV-2 lineage, the BA.2.86 variant, also emerged. BA.2.86 is phylogenetically distinct from other Omicron sublineages, accumulating over 30 amino acid mutations in its spike protein. Here, we examined the virological characteristics of the BA.2.86 variant. Our epidemic dynamics modeling suggested that the relative reproduction number of BA.2.86 is significantly higher than that of EG.5.1. Additionally, four clinically available antivirals were effective against BA...
January 22, 2024: Cell Host & Microbe
Ting Li, Ning Ding, Hanqing Guo, Rui Hua, Zehao Lin, Huohuan Tian, Yue Yu, Daiming Fan, Zuyi Yuan, Frank J Gonzalez, Yue Wu
Aspirin-related gastrointestinal damage is of growing concern. Aspirin use modulates the gut microbiota and associated metabolites, such as bile acids (BAs), but how this impacts intestinal homeostasis remains unclear. Herein, using clinical cohorts and aspirin-treated mice, we identified an intestinal microbe, Parabacteroides goldsteinii, whose growth is suppressed by aspirin. Mice supplemented with P. goldsteinii or its BA metabolite, 7-keto-lithocholic acid (7-keto-LCA), showed reduced aspirin-mediated damage of the intestinal niche and gut barrier, effects that were lost with a P...
January 11, 2024: Cell Host & Microbe
Ekaterina Buzun, Chia-Yun Hsu, Kristija Sejane, Renee E Oles, Adriana Vasquez Ayala, Luke R Loomis, Jiaqi Zhao, Leigh-Ana Rossitto, Dominic M McGrosso, David J Gonzalez, Lars Bode, Hiutung Chu
The early microbial colonization of the gastrointestinal tract can have long-term impacts on development and health. Keystone species, including Bacteroides spp., are prominent in early life and play crucial roles in maintaining the structure of the intestinal ecosystem. However, the process by which a resilient community is curated during early life remains inadequately understood. Here, we show that a single sialidase, NanH, in Bacteroides fragilis mediates stable occupancy of the intestinal mucosa in early life and regulates a commensal colonization program...
January 9, 2024: Cell Host & Microbe
Melanie Schirmer, Martin Stražar, Julian Avila-Pacheco, Daniel F Rojas-Tapias, Eric M Brown, Emily Temple, Amy Deik, Kevin Bullock, Sarah Jeanfavre, Kerry Pierce, Shen Jin, Rachele Invernizzi, Marie-Madlen Pust, Zach Costliow, David R Mack, Anne M Griffiths, Thomas Walters, Brendan M Boyle, Subra Kugathasan, Hera Vlamakis, Jeffrey Hyams, Lee Denson, Clary B Clish, Ramnik J Xavier
Understanding the role of the microbiome in inflammatory diseases requires the identification of microbial effector molecules. We established an approach to link disease-associated microbes to microbial metabolites by integrating paired metagenomics, stool and plasma metabolomics, and culturomics. We identified host-microbial interactions correlated with disease activity, inflammation, and the clinical course of ulcerative colitis (UC) in the Predicting Response to Standardized Colitis Therapy (PROTECT) pediatric inception cohort...
January 4, 2024: Cell Host & Microbe
Rofhiwa Nesamari, Millicent A Omondi, Richard Baguma, Maxine A Höft, Amkele Ngomti, Anathi A Nkayi, Asiphe S Besethi, Siyabulela F J Magugu, Paballo Mosala, Avril Walters, Gesina M Clark, Mathilda Mennen, Sango Skelem, Marguerite Adriaanse, Alba Grifoni, Alessandro Sette, Roanne S Keeton, Ntobeko A B Ntusi, Catherine Riou, Wendy A Burgers
Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against severe COVID-19. We examined T cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T cell memory responses in healthcare workers in South Africa (n = 39) who were vaccinated and experienced at least one SARS-CoV-2 infection...
January 4, 2024: Cell Host & Microbe
Thomas R Müller, Yu Gao, Jinghua Wu, Oriana Ribeiro, Puran Chen, Peter Bergman, Ola Blennow, Lotta Hansson, Stephan Mielke, Piotr Nowak, Jan Vesterbacka, Mira Akber, Gunnar Söderdahl, C I Edvard Smith, Karin Loré, Margaret Sällberg Chen, Per Ljungman, Hanna M Ingelman-Sundberg, Hans-Gustaf Ljunggren, Anders Österborg, Alessandro Sette, Alba Grifoni, Soo Aleman, Marcus Buggert
T cells are critical in mediating the early control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection. However, it remains unknown whether memory T cells can effectively cross-recognize new SARS-CoV-2 variants with a broad array of mutations, such as the emergent hypermutated BA.2.86 variant. Here, we report in two separate cohorts, including healthy controls and individuals with chronic lymphocytic leukemia, that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection or vaccination demonstrate resilient immune recognition of BA...
January 3, 2024: Cell Host & Microbe
Lingsha Cheng, Haoqian Wu, Xiaoying Cai, Youying Zhang, Siqi Yu, Yuanlong Hou, Zhe Yin, Qingyuan Yan, Qiong Wang, Taipeng Sun, Guangji Wang, Yonggui Yuan, Xueli Zhang, Haiping Hao, Xiao Zheng
Gene-environment interactions shape behavior and susceptibility to depression. However, little is known about the signaling pathways integrating genetic and environmental inputs to impact neurobehavioral outcomes. We report that gut G-protein-coupled receptor, Gpr35, engages a microbe-to-brain metabolic pathway to modulate neuronal plasticity and depressive behavior in mice. Psychological stress decreases intestinal epithelial Gpr35, genetic deletion of which induces depressive-like behavior in a microbiome-dependent manner...
January 3, 2024: Cell Host & Microbe
Jimin Cha, Tae-Gyun Kim, Euihyun Bhae, Ho-Jin Gwak, Yeajin Ju, Young Ho Choe, In-Hwan Jang, Youngae Jung, Sungmin Moon, Taehyun Kim, Wuseong Lee, Jung Sun Park, Youn Wook Chung, Siyoung Yang, Yong-Kook Kang, Young-Min Hyun, Geum-Sook Hwang, Won-Jae Lee, Mina Rho, Ji-Hwan Ryu
Although early life colonization of commensal microbes contributes to long-lasting immune imprinting in host tissues, little is known regarding the pathophysiological consequences of postnatal microbial tuning of cutaneous immunity. Here, we show that postnatal exposure to specific skin commensal Staphylococcus lentus (S. lentus) promotes the extent of atopic dermatitis (AD)-like inflammation in adults through priming of group 2 innate lymphoid cells (ILC2s). Early postnatal skin is dynamically populated by discrete subset of primed ILC2s driven by microbiota-dependent induction of thymic stromal lymphopoietin (TSLP) in keratinocytes...
January 3, 2024: Cell Host & Microbe
Weixin Ke, Yuyan Xie, Yingying Chen, Hao Ding, Leixin Ye, Haoning Qiu, Hao Li, Lanyue Zhang, Lei Chen, Xiuyun Tian, Zhenghao Shen, Zili Song, Xin Fan, Jian-Fa Zong, Zhengyan Guo, Xiaoyu Ma, Meng Xiao, Guojian Liao, Cui Hua Liu, Wen-Bing Yin, Zhiyang Dong, Feng Yang, Yuan-Ying Jiang, David S Perlin, Yihua Chen, Yu V Fu, Linqi Wang
Bacterial persisters, a subpopulation of genetically susceptible cells that are normally dormant and tolerant to bactericides, have been studied extensively because of their clinical importance. In comparison, much less is known about the determinants underlying fungicide-tolerant fungal persister formation in vivo. Here, we report that during mouse lung infection, Cryptococcus neoformans forms persisters that are highly tolerant to amphotericin B (AmB), the standard of care for treating cryptococcosis...
January 2, 2024: Cell Host & Microbe
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