Cas9 Cleavage of Viral Genomes Primes the Acquisition of New Immunological Memories.
Abstract Type II CRISPR-Cas systems defend prokaryotes from bacteriophage infection through the acquisition of short viral DNA sequences known as spacers, which are transcribed into short RNA guides to specify the targets of the Cas9 nuclease. To counter the potentially devastating propagation of escaper phages with mutations in the target sequences, the host population acquires many different spacers. Whether and how pre-existing spacers in type II systems affect the acquisition of new ones is unknown. Here, we demonstrate that previously acquired spacers promote additional spacer acquisition from the vicinity of...
Source: Cell Host and Microbe - September 27, 2019 Category: Microbiology Authors: Nussenzweig PM, McGinn J, Marraffini LA Tags: Cell Host Microbe Source Type: research

Bioremediation of a Common Product of Food Processing by a Human Gut Bacterium.
Abstract Dramatic increases in processed food consumption represent a global health threat. Maillard reaction products (MRPs), which are common in processed foods, form upon heat-induced reaction of amino acids with reducing sugars and include advanced glycation end products with deleterious health effects. To examine how processed foods affect the microbiota, we fed gnotobiotic mice, colonized with 54 phylogenetically diverse human gut bacterial strains, defined sugar-rich diets containing whey as the protein source or a matched amino acid mixture. Whey or ϵ-fructoselysine, an MRP in whey and many processed food...
Source: Cell Host and Microbe - September 24, 2019 Category: Microbiology Authors: Wolf AR, Wesener DA, Cheng J, Houston-Ludlam AN, Beller ZW, Hibberd MC, Giannone RJ, Peters SL, Hettich RL, Leyn SA, Rodionov DA, Osterman AL, Gordon JI Tags: Cell Host Microbe Source Type: research

A Phage Protein Aids Bacterial Symbionts in Eukaryote Immune Evasion.
Abstract Phages are increasingly recognized as important members of host-associated microbiomes, with a vast genomic diversity. The new frontier is to understand how phages may affect higher order processes, such as in the context of host-microbe interactions. Here, we use marine sponges as a model to investigate the interplay between phages, bacterial symbionts, and eukaryotic hosts. Using viral metagenomics, we find that sponges, although massively filtering seawater, harbor species-specific and even individually unique viral signatures that are taxonomically distinct from other environments. We further discover...
Source: Cell Host and Microbe - September 18, 2019 Category: Microbiology Authors: Jahn MT, Arkhipova K, Markert SM, Stigloher C, Lachnit T, Pita L, Kupczok A, Ribes M, Stengel ST, Rosenstiel P, Dutilh BE, Hentschel U Tags: Cell Host Microbe Source Type: research

A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge.
Abstract Passively administered broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have been shown to protect non-human primates (NHPs) against chimeric simian-human immunodeficiency virus (SHIV) infection. With data from multiple non-human primate SHIV challenge studies that used single bNAbs, we conducted a meta-analysis to examine the relationship between predicted serum 50% neutralization titer (ID50) against the challenge virus and infection outcome. In a logistic model that adjusts for bNAb epitopes and challenge viruses, serum ID50 had a highly significant effect on infection risk (p 
Source: Cell Host and Microbe - September 11, 2019 Category: Microbiology Authors: Pegu A, Borate B, Huang Y, Pauthner MG, Hessell AJ, Julg B, Doria-Rose NA, Schmidt SD, Carpp LN, Cully MD, Chen X, Shaw GM, Barouch DH, Haigwood NL, Corey L, Burton DR, Roederer M, Gilbert PB, Mascola JR, Huang Y Tags: Cell Host Microbe Source Type: research

The Nuclear Matrix Protein SAFA Surveils Viral RNA and Facilitates Immunity by Activating Antiviral Enhancers and Super-enhancers.
Abstract Pathogen pattern recognition receptors (PRRs) trigger innate immune responses to invading pathogens. All known PRRs for viral RNA have extranuclear localization. However, for many viruses, replication generates dsRNA in the nucleus. Here, we show that the nuclear matrix protein SAFA (also known as HnRNPU) functions as a nuclear viral dsRNA sensor for both DNA and RNA viruses. Upon recognition of viral dsRNA, SAFA oligomerizes and activates the enhancers of antiviral genes, including IFNB1. Moreover, SAFA is required for the activation of super-enhancers, which direct vigorous immune gene transcription to ...
Source: Cell Host and Microbe - September 11, 2019 Category: Microbiology Authors: Cao L, Liu S, Li Y, Yang G, Luo Y, Li S, Du H, Zhao Y, Wang D, Chen J, Zhang Z, Li M, Ouyang S, Gao X, Sun Y, Wang Z, Yang L, Lin R, Wang P, You F Tags: Cell Host Microbe Source Type: research

A Family of Dual-Activity Glycosyltransferase-Phosphorylases Mediates Mannogen Turnover and Virulence in Leishmania Parasites.
Abstract Parasitic protists belonging to the genus Leishmania synthesize the non-canonical carbohydrate reserve, mannogen, which is composed of β-1,2-mannan oligosaccharides. Here, we identify a class of dual-activity mannosyltransferase/phosphorylases (MTPs) that catalyze both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. Structural and phylogenic analysis shows that while the MTPs are structurally related to bacterial mannan phosphorylases, they constitute a distinct family of glycosyltransferases (GT108) that have likely been acquired by horizontal gene transfer ...
Source: Cell Host and Microbe - September 11, 2019 Category: Microbiology Authors: Sernee MF, Ralton JE, Nero TL, Sobala LF, Kloehn J, Vieira-Lara MA, Cobbold SA, Stanton L, Pires DEV, Hanssen E, Males A, Ward T, Bastidas LM, van der Peet PL, Parker MW, Ascher DB, Williams SJ, Davies GJ, McConville MJ Tags: Cell Host Microbe Source Type: research

CRISPR-Cas System of a Prevalent Human Gut Bacterium Reveals Hyper-targeting against Phages in a Human Virome Catalog.
Abstract Bacteriophages are abundant within the human gastrointestinal tract, yet their interactions with gut bacteria remain poorly understood, particularly with respect to CRISPR-Cas immunity. Here, we show that the type I-C CRISPR-Cas system in the prevalent gut Actinobacterium Eggerthella lenta is transcribed and sufficient for specific targeting of foreign and chromosomal DNA. Comparative analyses of E. lenta CRISPR-Cas systems across (meta)genomes revealed 2 distinct clades according to cas sequence similarity and spacer content. We assembled a human virome database (HuVirDB), encompassing 1,831 samples...
Source: Cell Host and Microbe - August 28, 2019 Category: Microbiology Authors: Soto-Perez P, Bisanz JE, Berry JD, Lam KN, Bondy-Denomy J, Turnbaugh PJ Tags: Cell Host Microbe Source Type: research

Recruitment of Adult Precursor Cells Underlies Limited Repair of the Infected Larval Midgut in Drosophila.
Abstract Surviving infection requires immune and repair mechanisms. Developing organisms face the additional challenge of integrating these mechanisms with tightly controlled developmental processes. The larval Drosophila midgut lacks dedicated intestinal stem cells. We show that, upon infection, larvae perform limited repair using adult midgut precursors (AMPs). AMPs differentiate in response to damage to generate new enterocytes, transiently depleting their pool. Developmental delay allows for AMP reconstitution, ensuring the completion of metamorphosis. Notch signaling is required for the differentiation of AMP...
Source: Cell Host and Microbe - August 28, 2019 Category: Microbiology Authors: Houtz P, Bonfini A, Bing X, Buchon N Tags: Cell Host Microbe Source Type: research

Bioengineered Human Organ-on-Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection.
net N Abstract Intestinal epithelial cells are constantly exposed to pathogens and mechanical forces. However, the impact of mechanical forces on infections leading to diarrheal diseases remains largely unknown. Here, we addressed whether flow and peristalsis impact the infectivity of the human pathogen Shigella within a 3D colonic epithelium using Intestine-Chip technology. Strikingly, infection is significantly increased and minimal bacterial loads are sufficient to invade enterocytes from the apical side and trigger loss of barrier integrity, thereby shifting the paradigm about early stage Shigella invasio...
Source: Cell Host and Microbe - August 27, 2019 Category: Microbiology Authors: Grassart A, Malardé V, Gobba S, Sartori-Rupp A, Kerns J, Karalis K, Marteyn B, Sansonetti P, Sauvonnet N Tags: Cell Host Microbe Source Type: research

HIV Rebound Is Predominantly Fueled by Genetically Identical Viral Expansions from Diverse Reservoirs.
Abstract Viral rebound upon stopping combined antiretroviral therapy poses a major barrier toward an HIV cure. Cellular and anatomical sources responsible for reinitiating viral replication remain a subject of ardent debate, despite extensive research efforts. To unravel the source of rebounding viruses, we conducted a large-scale HIV-STAR (HIV-1 sequencing before analytical treatment interruption to identify the anatomically relevant HIV reservoir) clinical trial. We collected samples from 11 participants and compared the genetic composition of (pro)viruses collected under treatment from different cellular a...
Source: Cell Host and Microbe - August 23, 2019 Category: Microbiology Authors: De Scheerder MA, Vrancken B, Dellicour S, Schlub T, Lee E, Shao W, Rutsaert S, Verhofstede C, Kerre T, Malfait T, Hemelsoet D, Coppens M, Dhondt A, De Looze D, Vermassen F, Lemey P, Palmer S, Vandekerckhove L Tags: Cell Host Microbe Source Type: research

Structural Basis for Tetherin Antagonism as a Barrier to Zoonotic Lentiviral Transmission.
n X Abstract Tetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 to downregulate tetherin via its DIWK motif. As human tetherin lacks DIWK, antagonism of tetherin by Nef is a barrier to simian-human transmission of non-human primate lentiviruses. To determine the molecular basis for tetherin counteraction, we reconstituted the AP-2 complex with a simian tetherin and SIV Nef and determined its structure by cryoelectron microscopy (cryo-EM). Nef refolds the first α-...
Source: Cell Host and Microbe - August 20, 2019 Category: Microbiology Authors: Buffalo CZ, Stürzel CM, Heusinger E, Kmiec D, Kirchhoff F, Hurley JH, Ren X Tags: Cell Host Microbe Source Type: research

Genome-wide Analysis of Salmonellaenterica serovar Typhi in Humanized Mice Reveals Key Virulence Features.
In this study, we use a high-density S. Typhi transposon library in hu-SRC-SCID mice to identify virulence loci using transposon-directed insertion site sequencing (TraDIS). Vi capsule, lipopolysaccharide (LPS), and aromatic amino acid biosynthesis were essential for virulence, along with the siderophore salmochelin. However, in contrast to the murine S. Typhimurium model, neither the PhoPQ two-component system nor the SPI-2 pathogenicity island was required for lethal S. Typhi infection, nor was the CdtB typhoid toxin. These observations highlight major differences in the pathogenesis of typhoid and non-typhoidal Salmonel...
Source: Cell Host and Microbe - August 20, 2019 Category: Microbiology Authors: Karlinsey JE, Stepien TA, Mayho M, Singletary LA, Bingham-Ramos LK, Brehm MA, Greiner DL, Shultz LD, Gallagher LA, Bawn M, Kingsley RA, Libby SJ, Fang FC Tags: Cell Host Microbe Source Type: research

A Delicate Balance between Bacterial Iron and Reactive Oxygen Species Supports Optimal C.  elegans Development.
A Delicate Balance between Bacterial Iron and Reactive Oxygen Species Supports Optimal C. elegans Development. Cell Host Microbe. 2019 Aug 14;: Authors: Zhang J, Li X, Olmedo M, Holdorf AD, Shang Y, Artal-Sanz M, Yilmaz LS, Walhout AJM Abstract Iron is an essential micronutrient for all forms of life; low levels of iron cause human disease, while too much iron is toxic. Low iron levels induce reactive oxygen species (ROS) by disruption of the heme and iron-sulfur cluster-dependent electron transport chain (ETC). To identify bacterial metabolites that affect development, we screened the Keio ...
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Zhang J, Li X, Olmedo M, Holdorf AD, Shang Y, Artal-Sanz M, Yilmaz LS, Walhout AJM Tags: Cell Host Microbe Source Type: research

Mother's Touch: Milk IgA and Protection from Necrotizing Enterocolitis.
Abstract Human milk feeding is associated with lower rates of necrotizing enterocolitis (NEC), but an understanding of mechanism is lacking. In recent work, Gopalakrishna et al. report that human infants who develop NEC first experience an increase in Enterobacteriaceae in the portion of the microbiota not bound to IgA. PMID: 31415742 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Dunne-Castagna VP, Taft DH Tags: Cell Host Microbe Source Type: research

Lipid Droplets Grease Enterovirus Replication.
Abstract Replication complexes of (+)RNA viruses of eukaryotes are associated with specialized membranous domains, termed replication organelles. How these structures develop is poorly understood. In a recent Cell paper, Laufman et al. (2019) reveal that enteroviruses recruit lipid droplets to support lipid synthesis required for the structural development of replication organelles. PMID: 31415743 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Belov GA, van Kuppeveld FJM Tags: Cell Host Microbe Source Type: research

Building Complexity: Making and Breaking Synthetic Subunits of the HIV Capsid.
g T Abstract In this issue of Cell Host & Microbe, Summers et al. (2019) use protein engineering to generate a toolbox of HIV-1 capsid oligomers. In an accompanying Cell Reports paper, Huang et al. (2019) use these oligomers to determine how the capsid engages the kinesin-1 adaptor protein FEZ1. PMID: 31415744 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: James LC, Böcking T Tags: Cell Host Microbe Source Type: research

m5C Goes Viral.
Abstract In this issue of Cell Host & Microbe, Courtney et al. (2019a) find that HIV-1 genomic RNA has much more m5C than cellular mRNA. Deleting the m5C "writer" NSUN2 decreases HIV-1 m5C levels, promotes translation of the HIV-1 5' gag gene, and alters splicing at the A2 site. PMID: 31415745 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Winans S, Beemon K Tags: Cell Host Microbe Source Type: research

Commensal Strains of Neisseria Use DNA to Poison Their Pathogenic Rivals.
Abstract Commensal bacteria can interfere with colonization of the host by infiltrating pathogens. In this issue of Cell Host & Microbe, Kim et al. (2019) describe an intriguing mechanism of colonization resistance driven by the mismatching of methylation patterns following uptake of commensal-derived DNA by pathogenic strains of Neisseria. PMID: 31415746 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Fleming BA, Mulvey MA Tags: Cell Host Microbe Source Type: research

In the Grand Scheme of Things: Identifying Reproducible Microbial Signatures in Dietary Intervention Studies.
Abstract Nutrition research is plagued by the reproducibility crisis. Reconciling nutrition studies involving microbiome data presents a modern challenge for researchers. In this issue of Cell Host & Microbe, Bisanz et al., 2019 demonstrate a comprehensive methodology for meta-analysis of microbiome sequence data from high-fat-diet intervention studies. PMID: 31415747 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Poole AC Tags: Cell Host Microbe Source Type: research

The Gut Feeling: GPCRs Enlighten the Way.
Abstract Host-microbiome interactions affect host physiology, but the underlying mechanisms are not well understood. Recent papers from Chen et al. (2019) and Colosimo et al. (2019) in this issue of Cell Host & Microbe demonstrate that metabolites produced by several members of the gut microbiota can efficiently activate host G protein-coupled receptors and influence host physiology. PMID: 31415748 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Pandey S, Maharana J, Shukla AK Tags: Cell Host Microbe Source Type: research

Stressed Out About Hormones: How Plants Orchestrate Immunity.
y J Abstract Plants are under relentless challenge by pathogenic bacteria, fungi, and oomycetes, for whom they provide a resource of living space and nutrients. Upon detection of pathogens, plants carry out multiple layers of defense response, orchestrated by a tightly organized network of hormones. In this review, we provide an overview of the phytohormones involved in immunity and the ways pathogens manipulate their biosynthesis and signaling pathways. We highlight recent developments, including the discovery of a defense signaling molecule, new insights into hormone biosynthesis, and the increasing importance o...
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Bürger M, Chory J Tags: Cell Host Microbe Source Type: research

Small RNAs - Big Players in Plant-Microbe Interactions.
Abstract Eukaryotic small RNAs (sRNAs) are short non-coding regulatory molecules that induce RNA interference (RNAi). During microbial infection, host RNAi machinery is highly regulated and contributes to reprogramming gene expression and balancing plant immunity and growth. While most sRNAs function endogenously, some can travel across organismal boundaries between hosts and microbes and silence genes in trans in interacting organisms, a mechanism called "cross-kingdom RNAi." During the co-evolutionary arms race between fungi and plants, some fungi developed a novel virulence mechanism, sending sRNAs as...
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Huang CY, Wang H, Hu P, Hamby R, Jin H Tags: Cell Host Microbe Source Type: research

Plant-Microbe Interactions Facing Environmental Challenge.
Abstract In the past four decades, tremendous progress has been made in understanding how plants respond to microbial colonization and how microbial pathogens and symbionts reprogram plant cellular processes. In contrast, our knowledge of how environmental conditions impact plant-microbe interactions is less understood at the mechanistic level, as most molecular studies are performed under simple and static laboratory conditions. In this review, we highlight research that begins to shed light on the mechanisms by which environmental conditions influence diverse plant-pathogen, plant-symbiont, and plant-microbiota ...
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Cheng YT, Zhang L, He SY Tags: Cell Host Microbe Source Type: research

The Plant "Resistosome": Structural Insights into Immune Signaling.
The Plant "Resistosome": Structural Insights into Immune Signaling. Cell Host Microbe. 2019 Aug 14;26(2):193-201 Authors: Burdett H, Bentham AR, Williams SJ, Dodds PN, Anderson PA, Banfield MJ, Kobe B Abstract Plant innate immunity is triggered via direct or indirect recognition of pathogen effectors by the NLR family immune receptors. Mechanistic understanding of plant NLR function has relied on structural information from individual NLR domains and inferences from studies on animal NLRs. Recent reports of the cryo-EM structures of the Arabidopsis plant immune receptor ZAR1 in monomeric ina...
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Burdett H, Bentham AR, Williams SJ, Dodds PN, Anderson PA, Banfield MJ, Kobe B Tags: Cell Host Microbe Source Type: research

Modular HIV-1 Capsid Assemblies Reveal Diverse Host-Capsid Recognition Mechanisms.
Abstract The HIV-1 capsid is an ordered protein shell that houses the viral genome during early infection. Its expansive surface consists of an ordered and interfacing array of capsid protein hexamers and pentamers that are recognized by numerous cellular proteins. Many of these proteins recognize specific, assembled capsid interfaces not present in unassembled capsid subunits. We used protein-engineering tools to capture diverse capsid assembly intermediates. We built a repertoire of capsid assemblies (ranging from two to 42 capsid protein molecules) that recreate the various surfaces in infectious capsids. These...
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Summers BJ, Digianantonio KM, Smaga SS, Huang PT, Zhou K, Gerber EE, Wang W, Xiong Y Tags: Cell Host Microbe Source Type: research

Epitranscriptomic Addition of m5C to HIV-1 Transcripts Regulates Viral Gene Expression.
Abstract How the covalent modification of mRNA ribonucleotides, termed epitranscriptomic modifications, alters mRNA function remains unclear. One issue has been the difficulty of quantifying these modifications. Using purified HIV-1 genomic RNA, we show that this RNA bears more epitranscriptomic modifications than the average cellular mRNA, with 5-methylcytosine (m5C) and 2'O-methyl modifications being particularly prevalent. The methyltransferase NSUN2 serves as the primary writer for m5C on HIV-1 RNAs. NSUN2 inactivation inhibits not only m5C addition to HIV-1 transcripts but also viral replicatio...
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Courtney DG, Tsai K, Bogerd HP, Kennedy EM, Law BA, Emery A, Swanstrom R, Holley CL, Cullen BR Tags: Cell Host Microbe Source Type: research

The Landscape of Genetic Content in the Gut and Oral Human Microbiome.
Abstract Despite substantial interest in the species diversity of the human microbiome and its role in disease, the scale of its genetic diversity, which is fundamental to deciphering human-microbe interactions, has not been quantified. Here, we conducted a cross-study meta-analysis of metagenomes from two human body niches, the mouth and gut, covering 3,655 samples from 13 studies. We found staggering genetic heterogeneity in the dataset, identifying a total of 45,666,334 non-redundant genes (23,961,508 oral and 22,254,436 gut) at the 95% identity level. Fifty percent of all genes were "singletons," or ...
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Tierney BT, Yang Z, Luber JM, Beaudin M, Wibowo MC, Baek C, Mehlenbacher E, Patel CJ, Kostic AD Tags: Cell Host Microbe Source Type: research

HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.
, Jones JJ, Zeng J, Ochsenbauer C, Nkolola JP, Stephenson KE, Chen B, Gnanakaran S, Bonsignori M, Williams LD, Haynes BF, Doria-Rose N, Mascola JR, Montefiori DC, Barouch DH, Korber B PMID: 31415756 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Bricault CA, Yusim K, Seaman MS, Yoon H, Theiler J, Giorgi EE, Wagh K, Theiler M, Hraber P, Macke JP, Kreider EF, Learn GH, Hahn BH, Scheid JF, Kovacs JM, Shields JL, Lavine CL, Ghantous F, Rist M, Bayne MG, Neubauer GH, McMahan K, Peng H, Chéneau C, Jon Tags: Cell Host Microbe Source Type: research

Redondoviridae, a Family of Small, Circular DNA Viruses of the Human Oro-Respiratory Tract Associated with Periodontitis and Critical Illness.
PMID: 31415757 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - August 14, 2019 Category: Microbiology Authors: Abbas AA, Taylor LJ, Dothard MI, Leiby JS, Fitzgerald AS, Khatib LA, Collman RG, Bushman FD Tags: Cell Host Microbe Source Type: research

Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition.
b W, Laudes M, Franke A, Huttenhower C Abstract Obesity and type 2 diabetes (T2D) are metabolic disorders that are linked to microbiome alterations. However, their co-occurrence poses challenges in disentangling microbial features unique to each condition. We analyzed gut microbiomes of lean non-diabetic (n = 633), obese non-diabetic (n = 494), and obese individuals with T2D (n = 153) from German population and metabolic disease cohorts. Microbial taxonomic and functional profiles were analyzed along with medical histories, serum metabolomics, biometrics, and dietary data. Obesity was associated wit...
Source: Cell Host and Microbe - August 1, 2019 Category: Microbiology Authors: Thingholm LB, Rühlemann MC, Koch M, Fuqua B, Laucke G, Boehm R, Bang C, Franzosa EA, Hübenthal M, Rahnavard A, Frost F, Lloyd-Price J, Schirmer M, Lusis AJ, Vulpe CD, Lerch MM, Homuth G, Kacprowski T, Schmidt CO, Nöthlings U, Karlsen TH, Lieb W, Laudes Tags: Cell Host Microbe Source Type: research

Commensal Neisseria Kill Neisseria gonorrhoeae through a DNA-Dependent Mechanism.
So M Abstract The mucosa is colonized with commensal Neisseria. Some of these niches are sites of infection for the STD pathogen Neisseria gonorrhoeae (Ngo). Given the antagonistic behavior of commensal bacteria toward their pathogenic relatives, we hypothesized that commensal Neisseria may negatively affect Ngo colonization. Here, we report that commensal species of Neisseria kill Ngo through a mechanism based on genetic competence and DNA methylation state. Specifically, commensal-triggered killing occurs when the pathogen takes up commensal DNA containing a methylation pattern that it does not recognize. Indee...
Source: Cell Host and Microbe - July 31, 2019 Category: Microbiology Authors: Kim WJ, Higashi D, Goytia M, Rendón MA, Pilligua-Lucas M, Bronnimann M, McLean JA, Duncan J, Trees D, Jerse AE, So M Tags: Cell Host Microbe Source Type: research

Mapping Interactions of Microbial Metabolites with Human G-Protein-Coupled Receptors.
Abstract Despite evidence linking the human microbiome to health and disease, how the microbiota affects human physiology remains largely unknown. Microbiota-encoded metabolites are expected to play an integral role in human health. Therefore, assigning function to these metabolites is critical to understanding these complex interactions and developing microbiota-inspired therapies. Here, we use large-scale functional screening of molecules produced by individual members of a simplified human microbiota to identify bacterial metabolites that agonize G-protein-coupled receptors (GPCRs). Multiple metabolites, includ...
Source: Cell Host and Microbe - July 30, 2019 Category: Microbiology Authors: Colosimo DA, Kohn JA, Luo PM, Piscotta FJ, Han SM, Pickard AJ, Rao A, Cross JR, Cohen LJ, Brady SF Tags: Cell Host Microbe Source Type: research

Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediate Local-Systemic Innate Immune Communication in Drosophila.
Abstract Interorgan immunological communication is critical to connect the local-systemic innate immune response and orchestrate a homeostatic host defense. However, the factors and their roles in this process remain unclear. We find Drosophila IMD response in guts can sequentially trigger a systemic IMD reaction in the fat body. Sugar alcohols of the polyol pathway are essential for the spatiotemporal regulation of gut-fat body immunological communication (GFIC). IMD activation in guts causes elevated levels of sorbitol and galactitol in hemolymph. Aldose reductase (AR) in hemocytes, the rate-limiting enzyme...
Source: Cell Host and Microbe - July 19, 2019 Category: Microbiology Authors: Yang S, Zhao Y, Yu J, Fan Z, Gong ST, Tang H, Pan L Tags: Cell Host Microbe Source Type: research

Meta-Analysis Reveals Reproducible Gut Microbiome Alterations in Response to a High-Fat Diet.
Abstract Multiple research groups have shown that diet impacts the gut microbiome; however, variability in experimental design and quantitative assessment have made it challenging to assess the degree to which similar diets have reproducible effects across studies. Through an unbiased subject-level meta-analysis framework, we re-analyzed 27 dietary studies including 1,101 samples from rodents and humans. We demonstrate that a high-fat diet (HFD) reproducibly changes gut microbial community structure. Finer taxonomic analysis revealed that the most reproducible signals of a HFD are Lactococcus species, which we exp...
Source: Cell Host and Microbe - July 12, 2019 Category: Microbiology Authors: Bisanz JE, Upadhyay V, Turnbaugh JA, Ly K, Turnbaugh PJ Tags: Cell Host Microbe Source Type: research

Cas13 Helps Bacteria Play Dead when the Enemy Strikes.
Abstract How RNA-targeting CRISPR-Cas13 functions as a phage defense system has been mysterious. Recently in Nature, Meeske et al. (2019) demonstrate that Cas13 provides potent immunity to dsDNA phages without cutting their genome. By sensing phage transcripts and destroying RNA nonspecifically to arrest the cell into dormancy, Cas13 provides herd immunity. PMID: 31295418 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Authors: Mendoza SD, Bondy-Denomy J Tags: Cell Host Microbe Source Type: research

Rapid Worldwide Emergence of Pathogenic Fungi.
Abstract The recent coverage in the mainstream media of global Candida auris outbreaks has provided the general public with an awareness of the unprecedented emergence rate of pathogenic fungi. Scientific communities need to collaboratively address this threat to public health. PMID: 31295419 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Authors: Rhodes J Tags: Cell Host Microbe Source Type: research

Surviving as a Community: Antibiotic Tolerance and Persistence in Bacterial Biofilms.
Abstract Biofilms are surface-associated bacterial communities that play both beneficial and harmful roles in nature, medicine, and industry. Tolerant and persister cells are thought to underlie biofilm-related bacterial recurrence in medical and industrial contexts. Here, we review recent progress aimed at understanding the mechanical features that drive biofilm resilience and the biofilm formation process at single-cell resolution. We discuss findings regarding mechanisms underlying bacterial tolerance and persistence in biofilms and how these phenotypes are linked to antibiotic resistance. New strategies f...
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Authors: Yan J, Bassler BL Tags: Cell Host Microbe Source Type: research

Precision Medicine Goes Microscopic: Engineering the Microbiome to Improve Drug Outcomes.
Abstract Despite the recognition, nearly a century ago, that the human microbiome plays a clinically relevant role in drug disposition, mechanistic insights, and translational applications are still limited. Here, we highlight the recent re-emergence of "pharmacomicrobiomics," which seeks to understand how inter-individual variations in the microbiome shape drug efficacy and side effect profiles. Multiple bacterial species, genes, and enzymes have already been implicated in the direct biotransformation of drugs, both from targeted case studies and from systematic computational and experimental analyses. ...
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Authors: Lam KN, Alexander M, Turnbaugh PJ Tags: Cell Host Microbe Source Type: research

Mast Cell Eavesdropping on Bacterial Communications.
Abstract Bacteria communicate through quorum sensing, which enables bacterial coordination of collective behaviors and environment-induced adaptations. In this issue of Cell Host & Microbe, Pundir et al. (2019) report that connective-tissue-type mast cells spy on bacterial communication by detecting the messenger molecules via their receptor Mrgprb2-MRGPRX2 to the host benefit. PMID: 31295422 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Authors: Kawakami T, Kasakura K Tags: Cell Host Microbe Source Type: research

Elucidating Mechanisms of Drug-Resistant Plasmodium falciparum.
Abstract Intensified treatment and control efforts since the early 2000s have dramatically reduced the burden of Plasmodium falciparum malaria. However, drug resistance threatens to derail this progress. In this review, we present four antimalarial resistance case studies that differ in timeline, technical approaches, mechanisms of action, and categories of resistance: chloroquine, sulfadoxine-pyrimethamine, artemisinin, and piperaquine. Lessons learned from prior losses of treatment efficacy, drug combinations, and control strategies will help advance mechanistic research into how P. falciparum parasites acq...
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Authors: Ross LS, Fidock DA Tags: Cell Host Microbe Source Type: research

The Impact of HIV-1 Drug Escape on the Global Treatment Landscape.
Abstract The rising prevalence of HIV drug resistance (HIVDR) could threaten gains made in combating the HIV epidemic and compromise the 90-90-90 target proposed by United Nations Programme on HIV/AIDS (UNAIDS) to have achieved virological suppression in 90% of all persons receiving antiretroviral therapy (ART) by the year 2020. HIVDR has implications for the persistence of HIV, the selection of current and future ART drug regimens, and strategies of vaccine and cure development. Focusing on drug classes that are in clinical use, this Review critically summarizes what is known about the mechanisms the virus utiliz...
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Authors: Collier DA, Monit C, Gupta RK Tags: Cell Host Microbe Source Type: research

Exciting Contributions to the Cryptosporidium Renaissance.
Abstract In this issue of Cell Host & Microbe, Wilke et al. (2019) describe an air liquid interface culture system supporting the complete life cycle of Cryptosporidium, while Sateriale et al. (2019) report an immunocompetent mouse model facilitating vaccination-induced protection. Together, these studies represent a powerful toolbox for Cryptosporidium research. PMID: 31295425 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Authors: Vijayan K, Kaushansky A Tags: Cell Host Microbe Source Type: research

Non-traditional Antibacterial Therapeutic Options and Challenges.
Abstract The global challenges presented by drug-resistant bacterial infections have stimulated much activity in finding new treatments. This review summarizes the progress and setbacks of non-traditional approaches intent on circumventing bacterial drug resistance. These approaches include targeting virulence via toxin production and virulence factor secretion, impeding bacterial adhesion to host cells and biofilm formation, interrupting or inhibiting bacterial communication, and downregulating virulence. Other strategies include immune evasion, microbiome-modifying therapies, and the employment of phages as trea...
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Authors: Theuretzbacher U, Piddock LJV Tags: Cell Host Microbe Source Type: research

The Landscape of Persistent Viral Genomes in ART-Treated SIV, SHIV, and HIV-2 Infections.
iciano RF Abstract Evaluation of HIV cure strategies is complicated by defective proviruses that persist in ART-treated patients but are irrelevant to cure. Non-human primates (NHP) are essential for testing cure strategies. However, the persisting proviral landscape in ART-treated NHPs is uncharacterized. Here, we describe viral genomes persisting in ART-treated, simian immunodeficiency virus (SIV)-infected NHPs, simian-human immunodeficiency virus (SHIV)-infected NHPs, and humans infected with HIV-2, an SIV-related virus. The landscapes of persisting SIV, SHIV, and HIV-2 genomes are also dominated by defect...
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Authors: Bender AM, Simonetti FR, Kumar MR, Fray EJ, Bruner KM, Timmons AE, Tai KY, Jenike KM, Antar AAR, Liu PT, Ho YC, Raugi DN, Seydi M, Gottlieb GS, Okoye AA, Del Prete GQ, Picker LJ, Mankowski JL, Lifson JD, Siliciano JD, Laird GM, Barouch DH, Clements JE, Si Tags: Cell Host Microbe Source Type: research

Overcoming Antibiotic Resistance.
Authors: Abstract We invited eleven experts in their fields to share their insights on the growing threats of antibiotic resistance, and how we, as a community, can address them. PMID: 31295428 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - July 10, 2019 Category: Microbiology Tags: Cell Host Microbe Source Type: research

A Connective Tissue Mast-Cell-Specific Receptor Detects Bacterial Quorum-Sensing Molecules and Mediates Antibacterial Immunity.
We report that mouse mast-cell-specific G-protein-coupled receptor Mrgprb2 and its human homolog MRGPRX2 are receptors for Gram-positive QSMs, including competence-stimulating peptide (CSP)-1. CSP-1 activates Mrgprb2 and MRGPRX2, triggering mast cell degranulation, which inhibits bacterial growth and prevents biofilm formation. Such antibacterial functions are reduced in Mrgprb2-deficient mast cells, while wild-type mast cells fail to inhibit the growth of bacterial strains lacking CSP-1. Mrgprb2-knockout mice exhibit reduced bacterial clearance, while pharmacologically activating Mrgprb2 in vivo eliminates bacteria a...
Source: Cell Host and Microbe - June 28, 2019 Category: Microbiology Authors: Pundir P, Liu R, Vasavda C, Serhan N, Limjunyawong N, Yee R, Zhan Y, Dong X, Wu X, Zhang Y, Snyder SH, Gaudenzio N, Vidal JE, Dong X Tags: Cell Host Microbe Source Type: research

ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection.
NJ Abstract The Cullin-RING E3 ligase (CRL) family is commonly hijacked by pathogens to redirect the host ubiquitin proteasome machinery to specific targets. During HIV infection, CRL5 is hijacked by HIV Vif to target viral restriction factors of the APOBEC3 family for ubiquitination and degradation. Here, using a quantitative proteomics approach, we identify the E3 ligase ARIH2 as a regulator of CRL5-mediated APOBEC3 degradation. The CUL5Vif/CBFß complex recruits ARIH2 where it acts to transfer ubiquitin directly to the APOBEC3 targets. ARIH2 is essential for CRL5-dependent HIV infectivity in primary CD4+ ...
Source: Cell Host and Microbe - June 24, 2019 Category: Microbiology Authors: Hüttenhain R, Xu J, Burton LA, Gordon DE, Hultquist JF, Johnson JR, Satkamp L, Hiatt J, Rhee DY, Baek K, Crosby DC, Frankel AD, Marson A, Harper JW, Alpi AF, Schulman BA, Gross JD, Krogan NJ Tags: Cell Host Microbe Source Type: research

A Genetically Tractable, Natural Mouse Model of Cryptosporidiosis Offers Insights into Host Protective Immunity.
pen B Abstract Cryptosporidium is a leading cause of diarrheal disease and an important contributor to early childhood mortality, malnutrition, and growth faltering. Older children in high endemicity regions appear resistant to infection, while previously unexposed adults remain susceptible. Experimental studies in humans and animals support the development of disease resistance, but we do not understand the mechanisms that underlie protective immunity to Cryptosporidium. Here, we derive an in vivo model of Cryptosporidium infection in immunocompetent C57BL/6 mice by isolating parasites from naturally infecte...
Source: Cell Host and Microbe - June 18, 2019 Category: Microbiology Authors: Sateriale A, Šlapeta J, Baptista R, Engiles JB, Gullicksrud JA, Herbert GT, Brooks CF, Kugler EM, Kissinger JC, Hunter CA, Striepen B Tags: Cell Host Microbe Source Type: research

A Stem-Cell-Derived Platform Enables Complete Cryptosporidium Development In  Vitro and Genetic Tractability.
A Stem-Cell-Derived Platform Enables Complete Cryptosporidium Development In Vitro and Genetic Tractability. Cell Host Microbe. 2019 Jun 18;: Authors: Wilke G, Funkhouser-Jones LJ, Wang Y, Ravindran S, Wang Q, Beatty WL, Baldridge MT, VanDussen KL, Shen B, Kuhlenschmidt MS, Kuhlenschmidt TB, Witola WH, Stappenbeck TS, Sibley LD Abstract Despite being a frequent cause of severe diarrheal disease in infants and an opportunistic infection in immunocompromised patients, Cryptosporidium research has lagged due to a lack of facile experimental methods. Here, we describe a platform for complete lif...
Source: Cell Host and Microbe - June 18, 2019 Category: Microbiology Authors: Wilke G, Funkhouser-Jones LJ, Wang Y, Ravindran S, Wang Q, Beatty WL, Baldridge MT, VanDussen KL, Shen B, Kuhlenschmidt MS, Kuhlenschmidt TB, Witola WH, Stappenbeck TS, Sibley LD Tags: Cell Host Microbe Source Type: research

Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity.
Abstract Given the immense antigenic load present in the microbiome, we hypothesized that microbiota mimotopes can be a persistent trigger in human autoimmunity via cross-reactivity. Using antiphospholipid syndrome (APS) as a model, we demonstrate cross-reactivity between non-orthologous mimotopes expressed by a common human gut commensal, Roseburia intestinalis (R. int), and T and B cell autoepitopes in the APS autoantigen β2-glycoprotein I (β2GPI). Autoantigen-reactive CD4+ memory T cell clones and an APS-derived, pathogenic monoclonal antibody cross-reacted with R. int mimotopes. C...
Source: Cell Host and Microbe - June 17, 2019 Category: Microbiology Authors: Ruff WE, Dehner C, Kim WJ, Pagovich O, Aguiar CL, Yu AT, Roth AS, Vieira SM, Kriegel C, Adeniyi O, Mulla MJ, Abrahams VM, Kwok WW, Nussinov R, Erkan D, Goodman AL, Kriegel MA Tags: Cell Host Microbe Source Type: research