Beating Them with Their Own Stick-Tick Uses Amidase of Bacterial Origin as Part of Its Immune Arsenal.
Abstract As vectors of microbial diseases in vertebrates, ticks are excellent at regulating bacterial proliferation in and around them. In a recent issue of Cell, Hayes et al. (2020) reveal acarid toxins of bacterial origin that help eliminate microbes that are pathogenic to black-legged ticks but commensal to their vertebrate hosts. PMID: 33444551 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - January 13, 2021 Category: Microbiology Authors: Mikaelyan A Tags: Cell Host Microbe Source Type: research

A Diamond in the Rough: IgA-Seq Signatures Stratify New Onset IBD.
Abstract Intestinal immunoglobulin (Ig)A binds to distinct commensals and pathobionts, but do these IgA-coated bacterial communities define clinical characteristics of inflammatory disease? In this issue of Cell Host & Microbe, Shapiro et al. comprehensively analyze IgA-coated bacteria in new onset inflammatory bowel disease (IBD), revealing their potential in guiding precision therapy and diagnostic stratification. PMID: 33444552 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - January 13, 2021 Category: Microbiology Authors: Lima S, Longman RS Tags: Cell Host Microbe Source Type: research

Dengue Vaccines: The Promise and Pitfalls of Antibody-Mediated Protection.
Abstract More than 390 million human dengue virus (DENV) infections occur each year, worldwide. Dengvaxia, a live-virus tetravalent vaccine from Sanofi Pasteur, was recently approved for human clinical use, although vaccine performance against the four DENV serotypes is highly variable. Other dengue vaccines in advanced clinical testing also demonstrate variability in efficacy. In this review, we outline the benefits and challenges of developing a safe, effective, and balanced DENV vaccine that can provide uniform protection against all four serotypes. Even though T cell biology plays an important role in est...
Source: Cell Host and Microbe - January 13, 2021 Category: Microbiology Authors: Martinez DR, Metz SW, Baric RS Tags: Cell Host Microbe Source Type: research

Mutation, Selection, and Bottlenecks in Polio Vaccine Reversion.
Abstract Troubled by an unstable world beset by new and emerging viruses? Virus evolution is here to help. Through detailed studies of poliovirus vaccine reversion to virulence, Valesano and colleagues remind us that some things in life can, indeed, be counted on. PMID: 33444554 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - January 13, 2021 Category: Microbiology Authors: Ebel GD Tags: Cell Host Microbe Source Type: research

Hiding in Plain Sight.
Abstract Microbes expertly manipulate hosts to their advantage, but few completely escape detection. In this issue of Cell Host & Microbe, Takaki et al. (2021) describe how Schistosoma mansoni eggs choreograph macrophage behaviors to promote efficient transmission of mature eggs, while immature eggs remain safely hidden in plain sight. PMID: 33444555 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - January 13, 2021 Category: Microbiology Authors: Smith TJ, Kowalski CH, Guillemin K Tags: Cell Host Microbe Source Type: research

The Intestinal Microbiota: Our Best Frenemy in Radiation-Induced Damages?
Abstract High-dose ionizing radiation used during cancer radiotherapy is associated with the induction of hematopoietic, gastrointestinal, and cerebrovascular injuries. In a recent Science issue, Guo et al. demonstrated that the gut microbiota-and its associated metabolites-play a central role in protecting against high-dose radiation. PMID: 33444556 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - January 13, 2021 Category: Microbiology Authors: Kordahi MC, Chassaing B Tags: Cell Host Microbe Source Type: research

Role of dietary fiber in the recovery of the human gut microbiome and its metabolome.
Abstract Gut microbiota metabolites may be important for host health, yet few studies investigate the correlation between human gut microbiome and production of fecal metabolites and their impact on the plasma metabolome. Since gut microbiota metabolites are influenced by diet, we performed a longitudinal analysis of the impact of three divergent diets, vegan, omnivore, and a synthetic enteral nutrition (EEN) diet lacking fiber, on the human gut microbiome and its metabolome, including after a microbiota depletion intervention. Omnivore and vegan, but not EEN, diets altered fecal amino acid levels by supporting th...
Source: Cell Host and Microbe - January 8, 2021 Category: Microbiology Authors: Tanes C, Bittinger K, Gao Y, Friedman ES, Nessel L, Paladhi UR, Chau L, Panfen E, Fischbach MA, Braun J, Xavier RJ, Clish CB, Li H, Bushman FD, Lewis JD, Wu GD Tags: Cell Host Microbe Source Type: research

Methotrexate impacts conserved pathways in diverse human gut bacteria leading to decreased host immune activation.
Abstract Immunomodulatory drugs can inhibit bacterial growth, yet their mechanism of action, spectrum, and clinical relevance remain unknown. Methotrexate (MTX), a first-line rheumatoid arthritis (RA) treatment, inhibits mammalian dihydrofolate reductase (DHFR), but whether it directly impacts gut bacteria is unclear. We show that MTX broadly alters the human gut microbiota. Drug sensitivity varied across strains, but the mechanism of action against DHFR appears conserved between mammalian and bacterial cells. RA patient microbiotas were sensitive to MTX, and changes in gut bacterial taxa and gene family abundance...
Source: Cell Host and Microbe - January 7, 2021 Category: Microbiology Authors: Nayak RR, Alexander M, Deshpande I, Stapleton-Gray K, Rimal B, Patterson AD, Ubeda C, Scher JU, Turnbaugh PJ Tags: Cell Host Microbe Source Type: research

Large-scale genome sequencing reveals the driving forces of viruses in microalgal evolution.
Abstract Being integral primary producers in diverse ecosystems, microalgal genomes could be mined for ecological insights, but representative genome sequences are lacking for many phyla. We cultured and sequenced 107 microalgae species from 11 different phyla indigenous to varied geographies and climates. This collection was used to resolve genomic differences between saltwater and freshwater microalgae. Freshwater species showed domain-centric ontology enrichment for nuclear and nuclear membrane functions, while saltwater species were enriched in organellar and cellular membrane functions. Further, marine specie...
Source: Cell Host and Microbe - December 31, 2020 Category: Microbiology Authors: Nelson DR, Hazzouri KM, Lauersen KJ, Jaiswal A, Chaiboonchoe A, Mystikou A, Fu W, Daakour S, Dohai B, Alzahmi A, Nobles D, Hurd M, Sexton J, Preston MJ, Blanchette J, Lomas MW, Amiri KMA, Salehi-Ashtiani K Tags: Cell Host Microbe Source Type: research

Immunoglobulin A Targets a Unique Subset of the Microbiota in Inflammatory Bowel Disease.
Abstract The immunopathogenesis of inflammatory bowel disease (IBD) has been attributed to a combination of host genetics and intestinal dysbiosis. Previous work in a small cohort of IBD patients suggested that pro-inflammatory bacterial taxa are highly coated with secretory immunoglobulin IgA. Using bacterial fluorescence-activated cell sorting coupled with 16S rRNA gene sequencing (IgA-SEQ), we profiled IgA coating of intestinal microbiota in a large cohort of IBD patients and identified bacteria associated with disease and treatment. Forty-three bacterial taxa displayed significantly higher IgA coating in IBD c...
Source: Cell Host and Microbe - December 31, 2020 Category: Microbiology Authors: Shapiro JM, de Zoete MR, Palm NW, Laenen Y, Bright R, Mallette M, Bu K, Bielecka AA, Xu F, Hurtado-Lorenzo A, Shah SA, Cho JH, LeLeiko NS, Sands BE, Flavell RA, Clemente JC Tags: Cell Host Microbe Source Type: research

Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies.
Abstract Candida auris is an emerging multi-drug-resistant human fungal pathogen. C. auris skin colonization results in environmental shedding, which underlies hospital transmissions, and predisposes patients to subsequent infections. We developed a murine skin topical exposure model for C. auris to dissect risk factors for colonization and to test interventions that might protect patients. We demonstrate that C. auris establishes long-term residence within the skin tissue compartment, which would elude clinical surveillance. The four clades of C. auris, with geographically distinct origins, di...
Source: Cell Host and Microbe - December 24, 2020 Category: Microbiology Authors: Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA Tags: Cell Host Microbe Source Type: research

Intranasal vaccination with a lentiviral vector protects against SARS-CoV-2 in preclinical animal models.
eau P Abstract To develop a vaccine candidate against coronavirus disease 2019 (COVID-19), we generated a lentiviral vector (LV) eliciting neutralizing antibodies against the Spike glycoprotein of SARS-CoV-2. Systemic vaccination by this vector in mice, in which the expression of the SARS-CoV-2 receptor hACE2 has been induced by transduction of respiratory tract cells by an adenoviral vector, confers only partial protection despite high levels of serum neutralizing activity. However, eliciting an immune response in the respiratory tract through an intranasal boost results in a>3 log10 decrease in the lung viral...
Source: Cell Host and Microbe - December 16, 2020 Category: Microbiology Authors: Ku MW, Bourgine M, Authié P, Lopez J, Nemirov K, Moncoq F, Noirat A, Vesin B, Nevo F, Blanc C, Souque P, Tabbal H, Simon E, Hardy D, Le Dudal M, Guinet F, Fiette L, Mouquet H, Anna F, Martin A, Escriou N, Majlessi L, Charneau P Tags: Cell Host Microbe Source Type: research

Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors.
ce CM Abstract The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has devastated the global economy and claimed more than 1.7 million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen SARS-CoV-2 at two physiologically relevant temperatures along with three related coronaviruses (human coronav...
Source: Cell Host and Microbe - December 16, 2020 Category: Microbiology Authors: Hoffmann HH, Sánchez-Rivera FJ, Schneider WM, Luna JM, Soto-Feliciano YM, Ashbrook AW, Le Pen J, Leal AA, Ricardo-Lax I, Michailidis E, Hao Y, Stenzel AF, Peace A, Zuber J, Allis CD, Lowe SW, MacDonald MR, Poirier JT, Rice CM Tags: Cell Host Microbe Source Type: research

Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways.
Abstract The intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EEC). EECs communicate nutritional information to the nervous system, but whether they also relay signals from intestinal microbes remains unknown. Using in vivo real-time measurements of EEC and nervous system activity in zebrafish, we discovered that the bacteria Edwardsiella tarda activate EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increase intestinal motility. Microbial, pharmacological, or optogenetic activation of Trpa1+EECs directly stimulates va...
Source: Cell Host and Microbe - December 16, 2020 Category: Microbiology Authors: Ye L, Bae M, Cassilly CD, Jabba SV, Thorpe DW, Martin AM, Lu HY, Wang J, Thompson JD, Lickwar CR, Poss KD, Keating DJ, Jordt SE, Clardy J, Liddle RA, Rawls JF Tags: Cell Host Microbe Source Type: research

The immune landscape in tuberculosis reveals populations linked to disease and latency.
, Kaushal D, Artyomov MN, Khader SA Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) latently infects approximately one-fourth of the world's population. The immune mechanisms that govern progression from latent (LTBI) to active pulmonary TB (PTB) remain poorly defined. Experimentally Mtb-infected non-human primates (NHP) mirror the disease observed in humans and recapitulate both PTB and LTBI. We characterized the lung immune landscape in NHPs with LTBI and PTB using high-throughput technologies. Three defining features of PTB in macaque lungs include the influx of plasmacytoid dendritic cel...
Source: Cell Host and Microbe - December 16, 2020 Category: Microbiology Authors: Esaulova E, Das S, Singh DK, Choreño-Parra JA, Swain A, Arthur L, Rangel-Moreno J, Ahmed M, Singh B, Gupta A, Fernández-López LA, de la Luz Garcia-Hernandez M, Bucsan A, Moodley C, Mehra S, García-Latorre E, Zuniga J, Atkinson J, Kaushal D, Artyomov M Tags: Cell Host Microbe Source Type: research

Varying the Constant: Mechanisms of Fc-Mediated Immunity to Influenza Virus.
Abstract Antibodies are typically thought to mediate antiviral immunity by blocking host-cell infection. However, immunoglobulin G (IgG) can also stimulate antiviral responses through its constant region. A recent study in Nature (Bournazos et al., 2020) shows that modifying Fc binding affinities to better target FcɣRIIa enhances the influenza CD8 T cell response. PMID: 33301713 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - December 9, 2020 Category: Microbiology Authors: Kastenschmidt JM, Wagar LE Tags: Cell Host Microbe Source Type: research

Microbial Respiration in the Colon: Using H2O2 to Catch Your Breath.
Abstract To colonize the nutritionally competitive environment of the gut, invading bacteria must utilize unique metabolites. Two reports in this issue of Cell Host & Microbe describe how Citrobacter rodentium and Escherichia coli leverage colonocyte derived H2O2 to drive two distinct respiratory pathways that support their proliferation in the mouse intestine. PMID: 33301714 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - December 9, 2020 Category: Microbiology Authors: Crowley SM, Vallance BA Tags: Cell Host Microbe Source Type: research

Plugging a Leak: How Phagosomes "Stretch" to Accommodate Pathogen Growth.
Plugging a Leak: How Phagosomes "Stretch" to Accommodate Pathogen Growth. Cell Host Microbe. 2020 Dec 09;28(6):774-775 Authors: Onyishi CU, Desanti GE, May RC Abstract Phagocytes engulf pathogens into a membrane bound compartment called a phagosome, but what happens when engulfed pathogens start growing? In this issue of Cell Host & Microbe,Westman et al. (2020) show that lysosomes fuse with phagosomes to maintain phagosomal membrane integrity as the fungal pathogen Candida albicans expands. PMID: 33301715 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - December 9, 2020 Category: Microbiology Authors: Onyishi CU, Desanti GE, May RC Tags: Cell Host Microbe Source Type: research

Fiber Sets up the Battleground for Intestinal Prevotella.
Abstract In this issue of Cell Host & Microbe, Gálvez et al. employed metagenomic and phylogenetic analysis to systemically characterize murine Prevotella spp. Isolation of representative strains identified key fitness determinants, including arabinoxylan utilization loci, in a dominant murine colonizing strain and conserved in human gut microbiota, collectively facilitating the understanding of niches in the gut microbiota. PMID: 33301716 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - December 9, 2020 Category: Microbiology Authors: Wu M, Kasper DL Tags: Cell Host Microbe Source Type: research

FRETing over SARS-CoV-2: Conformational Dynamics of the Spike Glycoprotein.
ee JE Abstract In this issue of Cell Host & Microbe, Lu et al. utilize single-molecule FRET to reveal the conformation dynamics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, showing transitions from a closed ground state to the open receptor-accessible conformation via an on-path intermediate. These insights into spike conformations will facilitate rational immunogen design. PMID: 33301717 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - December 9, 2020 Category: Microbiology Authors: Serrão VHB, Lee JE Tags: Cell Host Microbe Source Type: research

Anaerobic Respiration of NOX1-Derived Hydrogen Peroxide Licenses Bacterial Growth at the Colonic Surface.
AJ Abstract The colonic microbiota exhibits cross-sectional heterogeneity, but the mechanisms that govern its spatial organization remain incompletely understood. Here we used Citrobacter rodentium, a pathogen that colonizes the colonic surface, to identify microbial traits that license growth and survival in this spatial niche. Previous work showed that during colonic crypt hyperplasia, type III secretion system (T3SS)-mediated intimate epithelial attachment provides C. rodentium with oxygen for aerobic respiration. However, we find that prior to the development of colonic crypt hyperplasia, T3SS-mediated i...
Source: Cell Host and Microbe - December 9, 2020 Category: Microbiology Authors: Miller BM, Liou MJ, Zhang LF, Nguyen H, Litvak Y, Schorr EM, Jang KK, Tiffany CR, Butler BP, Bäumler AJ Tags: Cell Host Microbe Source Type: research

Automated Prediction and Annotation of Small Open Reading Frames in Microbial Genomes.
Abstract Small open reading frames (smORFs) and their encoded microproteins play central roles in microbes. However, there is a vast unexplored space of smORFs within human-associated microbes. A recent bioinformatic analysis used evolutionary conservation signals to enhance prediction of small protein families. To facilitate the annotation of specific smORFs, we introduce SmORFinder. This tool combines profile hidden Markov models of each smORF family and deep learning models that better generalize to smORF families not seen in the training set, resulting in predictions enriched for Ribo-seq translation signals. ...
Source: Cell Host and Microbe - December 2, 2020 Category: Microbiology Authors: Durrant MG, Bhatt AS Tags: Cell Host Microbe Source Type: research

Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition.
Abstract Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape m...
Source: Cell Host and Microbe - November 19, 2020 Category: Microbiology Authors: Greaney AJ, Starr TN, Gilchuk P, Zost SJ, Binshtein E, Loes AN, Hilton SK, Huddleston J, Eguia R, Crawford KHD, Dingens AS, Nargi RS, Sutton RE, Suryadevara N, Rothlauf PW, Liu Z, Whelan SPJ, Carnahan RH, Crowe JE, Bloom JD Tags: Cell Host Microbe Source Type: research

Integrative Imaging Reveals SARS-CoV-2-Induced Reshaping of Subcellular Morphologies.
We report 3D electron microscopy reconstructions of whole cells and subcellular compartments, revealing extensive fragmentation of the Golgi apparatus, alteration of the mitochondrial network and recruitment of peroxisomes to viral replication organelles formed by clusters of double-membrane vesicles (DMVs). These are tethered to the endoplasmic reticulum, providing insights into DMV biogenesis and spatial coordination of SARS-CoV-2 replication. Live cell imaging combined with an infection sensor reveals profound remodeling of cytoskeleton elements. Pharmacological inhibition of their dynamics suppresses SARS-CoV-2 replica...
Source: Cell Host and Microbe - November 17, 2020 Category: Microbiology Authors: Cortese M, Lee JY, Cerikan B, Neufeldt CJ, Oorschot VMJ, Köhrer S, Hennies J, Schieber NL, Ronchi P, Mizzon G, Romero-Brey I, Santarella-Mellwig R, Schorb M, Boermel M, Mocaer K, Beckwith MS, Templin RM, Gross V, Pape C, Tischer C, Frankish J, Horvat NK, Tags: Cell Host Microbe Source Type: research

Identification of Natural CRISPR Systems and Targets in the Human Microbiome.
r C Abstract Many bacteria resist invasive DNA by incorporating sequences into CRISPR loci, which enable sequence-specific degradation. CRISPR systems have been well studied from isolate genomes, but culture-independent metagenomics provide a new window into their diversity. We profiled CRISPR loci and cas genes in the body-wide human microbiome using 2,355 metagenomes, yielding functional and taxonomic profiles for 2.9 million spacers by aligning the spacer content to each sample's metagenome and corresponding gene families. Spacer and repeat profiles agree qualitatively with those from isolate genomes but expand...
Source: Cell Host and Microbe - November 16, 2020 Category: Microbiology Authors: Münch PC, Franzosa EA, Stecher B, McHardy AC, Huttenhower C Tags: Cell Host Microbe Source Type: research

The Early Evolution of Oral Poliovirus Vaccine Is Shaped by Strong Positive Selection and Tight Transmission Bottlenecks.
Abstract The emergence of circulating vaccine-derived polioviruses through evolution of the oral polio vaccine (OPV) poses a significant obstacle to polio eradication. Understanding the early genetic changes that occur as OPV evolves and transmits is important for preventing future outbreaks. Here, we use deep sequencing to define the evolutionary trajectories of type 2 OPV in a vaccine trial. By sequencing 497 longitudinal stool samples from 271 OPV2 recipients and household contacts, we were able to examine the extent of convergent evolution in vaccinated individuals and the amount of viral diversity that is tra...
Source: Cell Host and Microbe - November 12, 2020 Category: Microbiology Authors: Valesano AL, Taniuchi M, Fitzsimmons WJ, Islam MO, Ahmed T, Zaman K, Haque R, Wong W, Famulare M, Lauring AS Tags: Cell Host Microbe Source Type: research

A Bioinformatic Analysis of Integrative Mobile Genetic Elements Highlights Their Role in Bacterial Adaptation.
PMID: 33181077 [PubMed] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - November 11, 2020 Category: Microbiology Authors: Durrant MG, Li MM, Siranosian BA, Montgomery SB, Bhatt AS Tags: Cell Host Microbe Source Type: research

Ultra-low Dose Aerosol Infection of Mice with Mycobacterium tuberculosis More Closely Models Human Tuberculosis.
Abstract Tuberculosis (TB) is a heterogeneous disease manifesting in a subset of individuals infected with aerosolized Mycobacterium tuberculosis (Mtb). Unlike human TB, murine infection results in uniformly high lung bacterial burdens and poorly organized granulomas. To develop a TB model that more closely resembles human disease, we infected mice with an ultra-low dose (ULD) of between 1-3 founding bacteria, reflecting a physiologic inoculum. ULD-infected mice exhibited highly heterogeneous bacterial burdens, well-circumscribed granulomas that shared features with human granulomas, and prolonged Mtb containment ...
Source: Cell Host and Microbe - October 27, 2020 Category: Microbiology Authors: Plumlee CR, Duffy FJ, Gern BH, Delahaye JL, Cohen SB, Stoltzfus CR, Rustad TR, Hansen SG, Axthelm MK, Picker LJ, Aitchison JD, Sherman DR, Ganusov VV, Gerner MY, Zak DE, Urdahl KB Tags: Cell Host Microbe Source Type: research

Schistosoma mansoni Eggs Modulate the Timing of Granuloma Formation to Promote Transmission.
nan L Abstract Schistosome eggs provoke the formation of granulomas, organized immune aggregates, around them. For the host, the granulomatous response can be both protective and pathological. Granulomas are also postulated to facilitate egg extrusion through the gut lumen, a necessary step for parasite transmission. We used zebrafish larvae to visualize the granulomatous response to Schistosomamansoni eggs and inert egg-sized beads. Mature eggs rapidly recruit macrophages, which form granulomas within days. Beads also induce granulomas rapidly, through a foreign body response. Strikingly, immature eggs do not rec...
Source: Cell Host and Microbe - October 23, 2020 Category: Microbiology Authors: Takaki KK, Rinaldi G, Berriman M, Pagán AJ, Ramakrishnan L Tags: Cell Host Microbe Source Type: research

Exploration of Bacterial Bottlenecks and Streptococcus pneumoniae Pathogenesis by CRISPRi-Seq.
Abstract Streptococcus pneumoniae is an opportunistic human pathogen that causes invasive diseases, including pneumonia, with greater health risks upon influenza A virus (IAV) co-infection. To facilitate pathogenesis studies in vivo, we developed an inducible CRISPR interference system that enables genome-wide fitness testing in one sequencing step (CRISPRi-seq). We applied CRISPRi-seq to assess bottlenecks and identify pneumococcal genes important in a murine pneumonia model. A critical bottleneck occurs at 48 h with few bacteria causing systemic infection. This bottleneck is not present during IAV supe...
Source: Cell Host and Microbe - October 22, 2020 Category: Microbiology Authors: Liu X, Kimmey JM, Matarazzo L, de Bakker V, Van Maele L, Sirard JC, Nizet V, Veening JW Tags: Cell Host Microbe Source Type: research

Deep-Learning Resources for Studying Glycan-Mediated Host-Microbe Interactions.
Abstract Glycans, the most diverse biopolymer, are shaped by evolutionary pressures stemming from host-microbe interactions. Here, we present machine learning and bioinformatics methods to leverage the evolutionary information present in glycans to gain insights into how pathogens and commensals interact with hosts. By using techniques from natural language processing, we develop deep-learning models for glycans that are trained on a curated dataset of 19,299 unique glycans and can be used to study and predict glycan functions. We show that these models can be utilized to predict glycan immunogenicity and the path...
Source: Cell Host and Microbe - October 21, 2020 Category: Microbiology Authors: Bojar D, Powers RK, Camacho DM, Collins JJ Tags: Cell Host Microbe Source Type: research

Distinct Polysaccharide Utilization Determines Interspecies Competition between Intestinal Prevotella spp.
wig T Abstract Prevotella spp. are a dominant bacterial genus within the human gut. Multiple Prevotella spp. co-exist in some individuals, particularly those consuming plant-based diets. Additionally, Prevotella spp. exhibit variability in the utilization of diverse complex carbohydrates. To investigate the relationship between Prevotella competition and diet, we isolated Prevotella species from the mouse gut, analyzed their genomes and transcriptomes in vivo, and performed competition experiments between species in mice. Diverse dominant Prevotella species compete for similar metabolic niches in vivo, w...
Source: Cell Host and Microbe - October 13, 2020 Category: Microbiology Authors: Gálvez EJC, Iljazovic A, Amend L, Lesker TR, Renault T, Thiemann S, Hao L, Roy U, Gronow A, Charpentier E, Strowig T Tags: Cell Host Microbe Source Type: research

RTP4 Is a Potent IFN-Inducible Anti-flavivirus Effector Engaged in a Host-Virus Arms Race in Bats and Other Mammals.
Abstract Among mammals, bats are particularly rich in zoonotic viruses, including flaviviruses. Certain bat species can be productively yet asymptomatically infected with viruses that cause overt disease in other species. However, little is known about the antiviral effector repertoire in bats relative to other mammals. Here, we report the black flying fox receptor transporter protein 4 (RTP4) as a potent interferon (IFN)-inducible inhibitor of human pathogens in the Flaviviridae family, including Zika, West Nile, and hepatitis C viruses. Mechanistically, RTP4 associates with the flavivirus replicase, binds viral ...
Source: Cell Host and Microbe - October 13, 2020 Category: Microbiology Authors: Boys IN, Xu E, Mar KB, De La Cruz-Rivera PC, Eitson JL, Moon B, Schoggins JW Tags: Cell Host Microbe Source Type: research

A Comprehensive Subcellular Atlas of the Toxoplasma Proteome via hyperLOPIT Provides Spatial Context for Protein Functions.
Abstract Apicomplexan parasites cause major human disease and food insecurity. They owe their considerable success to highly specialized cell compartments and structures. These adaptations drive their recognition, nondestructive penetration, and elaborate reengineering of the host's cells to promote their growth, dissemination, and the countering of host defenses. The evolution of unique apicomplexan cellular compartments is concomitant with vast proteomic novelty. Consequently, half of apicomplexan proteins are unique and uncharacterized. Here, we determine the steady-state subcellular location of thousands of pr...
Source: Cell Host and Microbe - October 8, 2020 Category: Microbiology Authors: Barylyuk K, Koreny L, Ke H, Butterworth S, Crook OM, Lassadi I, Gupta V, Tromer E, Mourier T, Stevens TJ, Breckels LM, Pain A, Lilley KS, Waller RF Tags: Cell Host Microbe Source Type: research

Mining the Antibody Repertoire for Solutions to SARS-CoV-2.
Abstract In this issue of Cell Host & Microbe, Nielsen and colleagues sequence antibody repertoires of patients with severe COVID-19 to reveal potentially convergent features on the background of a larger, polyclonal response. Their findings suggest that, as databases improve, it may be possible to monitor virus-specific B cells after infection or vaccination using antibody sequencing. PMID: 33031765 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - October 7, 2020 Category: Microbiology Authors: Meng W, Rosenfeld AM, Luning Prak ET Tags: Cell Host Microbe Source Type: research

The Enemy of my Enemy: Bacterial Competition in the Cystic Fibrosis Lung.
Abstract Bacterial competition within host-associated polymicrobial communities shapes their composition, often with far-reaching consequences for human health. In this issue of Cell Host & Microbe, Perault et al. reveal how competition between two opportunistic pathogens could account for the epidemiology of chronic lung infections in people with cystic fibrosis. PMID: 33031766 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - October 7, 2020 Category: Microbiology Authors: Kazmierczak BI Tags: Cell Host Microbe Source Type: research

Unwanted Feedback: Malaria Antibodies Hinder Vaccine Boosting.
Abstract Whole-organism vaccination is a promising approach to prevent malaria. In this issue of Cell Host & Microbe, McNamara and colleagues identify epitope masking as a hindrance to antibody boosting after repeated administration of attenuated Plasmodium falciparum sporozoite vaccine. PMID: 33031767 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - October 7, 2020 Category: Microbiology Authors: Coelho CH, Duffy PE Tags: Cell Host Microbe Source Type: research

Recipe for Zoonosis: How Influenza Virus Leaps into Human Circulation.
Abstract The features that permit or prevent a virus from becoming a zoonotic threat is an ongoing area of investigation. In this issue of Cell Host & Microbe, Herfst et al. and Henritzi et al. help define the molecular and host determinants of influenza virus spillover from animal to human populations. PMID: 33031768 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - October 7, 2020 Category: Microbiology Authors: Honce R, Schultz-Cherry S Tags: Cell Host Microbe Source Type: research

The Biology of the Intestinal Intracellular Parasite Cryptosporidium.
pen B Abstract Cryptosporidium emerged as a leading global cause of severe diarrheal disease in children. The parasite occupies a unique intracellular niche at the brush border of intestinal epithelial cells, where it undergoes a complex sexual life cycle. How this life cycle unfolds and how host and parasite interact remain largely to be discovered. A series of technical advances now offer genetic and immunological tools for mechanistic investigation of the parasite. Here we introduce the pathogen and disease and highlight important questions to tackle onward. We invite scientists to consider this versatile paras...
Source: Cell Host and Microbe - October 7, 2020 Category: Microbiology Authors: Guérin A, Striepen B Tags: Cell Host Microbe Source Type: research

Hemagglutinin Traits Determine Transmission of Avian A/H10N7 Influenza Virus between Mammals.
Abstract In 2014, an outbreak of avian A/H10N7 influenza virus occurred among seals along North-European coastal waters, significantly impacting seal populations. Here, we examine the cross-species transmission and mammalian adaptation of this influenza A virus, revealing changes in the hemagglutinin surface protein that increase stability and receptor binding. The seal A/H10N7 virus was aerosol or respiratory droplet transmissible between ferrets. Compared with avian H10 hemagglutinin, seal H10 hemagglutinin showed stronger binding to the human-type sialic acid receptor, with preferential binding to α2,6-li...
Source: Cell Host and Microbe - October 7, 2020 Category: Microbiology Authors: Herfst S, Zhang J, Richard M, McBride R, Lexmond P, Bestebroer TM, Spronken MIJ, de Meulder D, van den Brand JM, Rosu ME, Martin SR, Gamblin SJ, Xiong X, Peng W, Bodewes R, van der Vries E, Osterhaus ADME, Paulson JC, Skehel JJ, Fouchier RAM Tags: Cell Host Microbe Source Type: research

Recovery of the Gut Microbiota after Antibiotics Depends on Host Diet, Community Context, and Environmental Reservoirs.
ng KC PMID: 33031771 [PubMed] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - October 7, 2020 Category: Microbiology Authors: Ng KM, Aranda-Díaz A, Tropini C, Frankel MR, Van Treuren W, O'Loughlin CT, Merrill BD, Yu FB, Pruss KM, Oliveira RA, Higginbottom SK, Neff NF, Fischbach MA, Xavier KB, Sonnenburg JL, Huang KC Tags: Cell Host Microbe Source Type: research

Lysosome Fusion Maintains Phagosome Integrity during Fungal Infection.
Abstract Phagosomes must maintain membrane integrity to exert their microbicidal function. Some microorganisms, however, survive and grow within phagosomes. In such instances, phagosomes must expand to avoid rupture and microbial escape. We studied whether phagosomes regulate their size to preserve integrity during infection with the fungal pathogen Candida albicans. Phagosomes release calcium as C. albicans hyphae elongate, inducing lysosome recruitment and insertion, thereby increasing the phagosomal surface area. As hyphae grow, the expanding phagosome consumes the majority of free lysosomes. Simultaneously, ly...
Source: Cell Host and Microbe - September 29, 2020 Category: Microbiology Authors: Westman J, Walpole GFW, Kasper L, Xue BY, Elshafee O, Hube B, Grinstein S Tags: Cell Host Microbe Source Type: research

Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2.
ish CA, Boyd SD Abstract B cells are critical for the production of antibodies and protective immunity to viruses. Here we show that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) display early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify convergence of antibody sequences across SARS-CoV-2-in...
Source: Cell Host and Microbe - September 2, 2020 Category: Microbiology Authors: Nielsen SCA, Yang F, Jackson KJL, Hoh RA, Röltgen K, Jean GH, Stevens BA, Lee JY, Rustagi A, Rogers AJ, Powell AE, Hunter M, Najeeb J, Otrelo-Cardoso AR, Yost KE, Daniel B, Nadeau KC, Chang HY, Satpathy AT, Jardetzky TS, Kim PS, Wang TT, Pinsky BA, Blish Tags: Cell Host Microbe Source Type: research

Human-Gut-DNA Virome Variations across Geography, Ethnicity, and Urbanization.
This study highlights population-based variations and the importance of host and environmental factors in shaping the DNA virome in the human gut. PMID: 32910902 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - September 1, 2020 Category: Microbiology Authors: Zuo T, Sun Y, Wan Y, Yeoh YK, Zhang F, Cheung CP, Chen N, Luo J, Wang W, Sung JJY, Chan PKS, Wang K, Chan FKL, Miao Y, Ng SC Tags: Cell Host Microbe Source Type: research

Mothers of Preterm Infants Have Individualized Breast Milk Microbiota that Changes Temporally Based on Maternal Characteristics.
Abstract Mother's milk contains complex microbial communities thought to be important for colonizing a preterm infant's gastrointestinal tract. However, little is known about the microbiota in the preterm mother's milk and factors influencing its composition. We characterized the temporal dynamics of microbial communities in 490 breast milk samples from 86 mothers of preterm infants (born
Source: Cell Host and Microbe - August 30, 2020 Category: Microbiology Authors: Asbury MR, Butcher J, Copeland JK, Unger S, Bando N, Comelli EM, Forte V, Kiss A, LeMay-Nedjelski L, Sherman PM, Stintzi A, Tomlinson C, Wang PW, O'Connor DL Tags: Cell Host Microbe Source Type: research

Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor.
Abstract The SARS-CoV-2 betacoronavirus uses its highly glycosylated trimeric Spike protein to bind to the cell surface receptor angiotensin converting enzyme 2 (ACE2) glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2. We combined this information with bioinformatics analyses of natural variants and with existing 3D structures of both glycoproteins to generate molecular dynamics simulations of each glycoprotein both alon...
Source: Cell Host and Microbe - August 23, 2020 Category: Microbiology Authors: Zhao P, Praissman JL, Grant OC, Cai Y, Xiao T, Rosenbalm KE, Aoki K, Kellman BP, Bridger R, Barouch DH, Brindley MA, Lewis NE, Tiemeyer M, Chen B, Woods RJ, Wells L Tags: Cell Host Microbe Source Type: research

Legionella-Infected Macrophages Engage the Alveolar Epithelium to Metabolically Reprogram Myeloid Cells and Promote Antibacterial Inflammation.
Abstract Alveolar macrophages are among the first immune cells that respond to inhaled pathogens. However, numerous pathogens block macrophage-intrinsic immune responses, making it unclear how robust antimicrobial responses are generated. The intracellular bacterium Legionella pneumophila inhibits host translation, thereby impairing cytokine production by infected macrophages. Nevertheless, Legionella-infected macrophages induce an interleukin-1 (IL-1)-dependent inflammatory cytokine response by recruited monocytes and other cells that controls infection. How IL-1 directs these cells to produce inflammatory cytoki...
Source: Cell Host and Microbe - August 19, 2020 Category: Microbiology Authors: Liu X, Boyer MA, Holmgren AM, Shin S Tags: Cell Host Microbe Source Type: research

The Gut Virome Database Reveals Age-Dependent Patterns of Virome Diversity in the Human Gut.
Abstract The gut microbiome profoundly affects human health and disease, and their infecting viruses are likely as important, but often missed because of reference database limitations. Here, we (1) built a human Gut Virome Database (GVD) from 2,697 viral particle or microbial metagenomes from 1,986 individuals representing 16 countries, (2) assess its effectiveness, and (3) report a meta-analysis that reveals age-dependent patterns across healthy Westerners. The GVD contains 33,242 unique viral populations (approximately species-level taxa) and improves average viral detection rates over viral RefSeq and IMG/VR n...
Source: Cell Host and Microbe - August 19, 2020 Category: Microbiology Authors: Gregory AC, Zablocki O, Zayed AA, Howell A, Bolduc B, Sullivan MB Tags: Cell Host Microbe Source Type: research

Programing of an Intravascular Immune Firewall by the Gut Microbiota Protects against Pathogen Dissemination during Infection.
Abstract Eradication of pathogens from the bloodstream is critical to prevent disseminated infections and sepsis. Kupffer cells in the liver form an intravascular firewall that captures and clears pathogens from the blood. Here, we show that the catching and killing of circulating pathogens by Kupffer cells in vivo are promoted by the gut microbiota through commensal-derived D-lactate that reaches the liver via the portal vein. The integrity of this Kupffer cell-mediated intravascular firewall requires continuous crosstalk with gut commensals, as microbiota depletion with antibiotics leads to a failure of pat...
Source: Cell Host and Microbe - August 11, 2020 Category: Microbiology Authors: McDonald B, Zucoloto AZ, Yu IL, Burkhard R, Brown K, Geuking MB, McCoy KD Tags: Cell Host Microbe Source Type: research

Microbial Mind Control.
Abstract Every animal is in constant communication with populations of microbes. In a recent study, O'Donnell and colleagues (2020) uncover an inter-domain conversation, defining a relationship in which a non-pathogenic microbe directly synthesizes a signal that alters host behavior for a mutually beneficial outcome. PMID: 32791104 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - August 11, 2020 Category: Microbiology Authors: Matty MA, Chalasani SH Tags: Cell Host Microbe Source Type: research