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In a recent Cell paper, Yehl et al., 2019 find that bacteriophage T3 binds its host via four distal loops on the tail fiber. Randomization of these regions yield bacteriophage libraries capable of infecting resistant bacteria and preventing further resistance. These strategies may generate phage capable of infecting new hosts.
The diet-microbiome interaction can positively or negatively affect our health depending on dietary habits. In this issue of Cell Host & Microbe, Wolf et al. (2019) highlight the beneficial roles of gut commensal Collinsella in degrading potentially toxic food contaminants, called Maillard reaction products, found in processed foods.
The viral fraction of the human gut microbiota, or virome, has been studied in a limited capacity. In this issue of Cell Host & Microbe, Shkoporov et al. (2019) perform a longitudinal study with database-independent clustering of bacteriophage genomes and de novo taxonomic classification, increasing our understanding of the virome.
Bacteriophages, viruses that infect bacteria, are the most abundant biological entities within the holobiont. In this issue of Cell Host & Microbe, Jahn et al. (2019) describe a group of phages that can suppress immune cell function in marine sponges using secreted ankyrin proteins. They call these phages Ankyphages.
Calcium is an abundant intracellular ion, and calcium homeostasis plays crucial roles in several cellular processes. The calcineurin signaling cascade is one of the major pathways governed by intracellular calcium. Calcineurin, a conserved protein from yeast to humans, is a calcium-calmodulin-dependent serine-threonine-specific phosphatase that orchestrates cellular stress responses. In eukaryotic microbial pathogens, calcineurin controls essential virulence pathways, such as the ability to grow at host tem...
Toxoplasma can reach distant organs, especially the brain, leading to a lifelong chronic phase. However, genes involved in related in vivo processes are currently unknown. Here, we use focused CRISPR libraries to identify Toxoplasma genes that affect in vivo fitness. We focus on TgWIP, whose deletion affects Toxoplasma dissemination to distant organs. We show that TgWIP is secreted into the host cell upon invasion and interacts with the host WAVE regulatory complex and SHP2 phosphatase, both of which regu...
14-3-3 protein family members facilitate the translocation of RIG-I-like receptors (RLRs) to organelles that mediate downstream RLR signaling, leading to interferon production. 14-3-3ϵ promotes the cytosolic-to-mitochondrial translocation of RIG-I, while 14-3-3η facilitates MDA5 translocation to mitochondria. We show that the NS3 protein of Zika virus (ZIKV) antagonizes antiviral gene induction by RIG-I and MDA5 by binding to and sequestering the scaffold proteins 14-3-3ϵ and 14-3-3η. 14-3-3-binding is ...
Phage defense systems are often found on mobile genetic elements (MGEs), where they constitutively defend against invaders or are induced to respond to new assaults. Phage satellites, one type of MGE, are induced during phage infection to promote their own transmission, reducing phage production and protecting their hosts in the process. One such satellite in Vibrio cholerae, phage-inducible chromosomal island-like element (PLE), sabotages the lytic phage ICP1, which triggers PLE excision from the bacterial...
The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterized, and their roles in shaping the gut microbiome and in impacting on human health remain poorly understood. We performed longitudinal metagenomic analysis of fecal viruses in healthy adults that reveal high temporal stability, individual specificity, and correlation with the bacterial microbiome. Using a database-independent approach that uses most of the sequencing data, we uncovered the existence of a ...
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 sourc...
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 dem...
In this issue of Cell Host & Microbe, Buffalo et al. describe a cryo-EM structure of SIV Nef complexed with AP-2 and tetherin. The structure helps explain why human tetherin is Nef-resistant and why lentiviruses that successfully emerged in humans (HIV-1 and HIV-2) had to evolve novel anti-tetherin strategies.
Because Drosophila larvae do not possess intestinal stem cells, it is unknown how damaged gut cells are replenished. In this issue of Cell Host & Microbe, Houtz et al. (2019) show that larvae have a unique gut repair mechanism that involves borrowing stem cells originally reserved for adult gut formation.
In this issue of Cell Host & Microbe, Karlinsey et al. (2019) combine TraDIS with humanized mice to identify genes required for early replication of Salmonella Typhi in vivo. Surprisingly, some expected virulence traits and genes appear dispensable in the replication of S. Typhi, supporting findings from a recent human challenge study by Gibani et al. (2019).
Studies of the intestinal microbial environment largely focus on microbial taxonomy, without clarifying their health benefits. Two recent studies (Raman et al. and Gehrig et al.) classify microbial environments into "ecogroups" that provide insight into their metabolic and/or nutritional pathways and how this can be used for interventions in malnourished children.
The inexorable emergence of mosquito-borne arboviruses and the failure of traditional vector control methods to prevent their transmission have triggered the development of alternative entomological interventions to render mosquito populations incapable of carrying arboviruses. Here, we use a theoretical framework to argue that decreasing mosquito tolerance to arbovirus infection could be a more evolutionarily sustainable disease control strategy than increasing mosquito resistance. Increasing resistance is...
The role of gut microbes in health and disease has often been surmised from stool, which is easily sampled and rich in microbial diversity, density, and abundance. Microbial analyses of stool have been accepted as measures to determine the relationship of gut microbiomes with host health and disease, based on the belief that it represents all microbial populations throughout the gut. However, functional heterogeneity of each gastrointestinal tract (GIT) segment gives rise to regional differences in gut micr...
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...
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...
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...
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.
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.
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.