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Nature Microbiology

Corina Beerli, Artur Yakimovich, Samuel Kilcher, Glennys V Reynoso, Gotthold Fläschner, Daniel J Müller, Heather D Hickman, Jason Mercer
Cell motility is essential for viral dissemination1 . Vaccinia virus (VACV), a close relative of smallpox virus, is thought to exploit cell motility as a means to enhance the spread of infection1 . A single viral protein, F11L, contributes to this by blocking RhoA signalling to facilitate cell retraction2 . However, F11L alone is not sufficient for VACV-induced cell motility, indicating that additional viral factors must be involved. Here, we show that the VACV epidermal growth factor homologue, VGF, promotes infected cell motility and the spread of viral infection...
November 12, 2018: Nature Microbiology
Florian Full, Michiel van Gent, Konstantin M J Sparrer, Cindy Chiang, Matthew A Zurenski, Myriam Scherer, Norbert H Brockmeyer, Lucie Heinzerling, Michael Stürzl, Klaus Korn, Thomas Stamminger, Armin Ensser, Michaela U Gack
Tripartite motif (TRIM) proteins mediate antiviral host defences by either directly targeting viral components or modulating innate immune responses. Here we identify a mechanism of antiviral restriction in which a TRIM E3 ligase controls viral replication by regulating the structure of host cell centrosomes and thereby nuclear lamina integrity. Through RNAi screening we identified several TRIM proteins, including TRIM43, that control the reactivation of Kaposi's sarcoma-associated herpesvirus. TRIM43 was distinguished by its ability to restrict a broad range of herpesviruses and its profound upregulation during herpesvirus infection as part of a germline-specific transcriptional program mediated by the transcription factor DUX4...
November 12, 2018: Nature Microbiology
Adam Z Cheng, Jaime Yockteng-Melgar, Matthew C Jarvis, Natasha Malik-Soni, Ivan Borozan, Michael A Carpenter, Jennifer L McCann, Diako Ebrahimi, Nadine M Shaban, Edyta Marcon, Jack Greenblatt, William L Brown, Lori Frappier, Reuben S Harris
The apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like (APOBEC) family of single-stranded DNA (ssDNA) cytosine deaminases provides innate immunity against virus and transposon replication1-4 . A well-studied mechanism is APOBEC3G restriction of human immunodeficiency virus type 1, which is counteracted by a virus-encoded degradation mechanism1-4 . Accordingly, most work has focused on retroviruses with obligate ssDNA replication intermediates and it is unclear whether large double-stranded DNA (dsDNA) viruses may be similarly susceptible to restriction...
November 12, 2018: Nature Microbiology
Karthik Subramanian, Daniel R Neill, Hesham A Malak, Laura Spelmink, Shadia Khandaker, Giorgia Dalla Libera Marchiori, Emma Dearing, Alun Kirby, Marie Yang, Adnane Achour, Johan Nilvebrant, Per-Åke Nygren, Laura Plant, Aras Kadioglu, Birgitta Henriques-Normark
Streptococcus pneumoniae (the pneumococcus) is a major cause of mortality and morbidity globally, and the leading cause of death in children under 5 years old. The pneumococcal cytolysin pneumolysin (PLY) is a major virulence determinant known to induce pore-dependent pro-inflammatory responses. These inflammatory responses are driven by PLY-host cell membrane cholesterol interactions, but binding to a host cell receptor has not been previously demonstrated. Here, we discovered a receptor for PLY, whereby pro-inflammatory cytokine responses and Toll-like receptor signalling are inhibited following PLY binding to the mannose receptor C type 1 (MRC-1) in human dendritic cells and mouse alveolar macrophages...
November 12, 2018: Nature Microbiology
Ninghai Gan, Ernesto S Nakayasu, Peter J Hollenbeck, Zhao-Qing Luo
The bacterial pathogen Legionella pneumophila modulates host immunity using effectors translocated by its Dot/Icm transporter to facilitate its intracellular replication. A number of these effectors employ diverse mechanisms to interfere with protein ubiquitination, a post-translational modification essential for immunity. Here, we have found that L. pneumophila induces monoubiquitination of the E2 enzyme UBE2N by its Dot/Icm substrate MavC(Lpg2147). We demonstrate that MavC is a transglutaminase that catalyses covalent linkage of ubiquitin to Lys92 and Lys94 of UBE2N via Gln40 ...
November 12, 2018: Nature Microbiology
Tracey Goldstein, Simon J Anthony, Aiah Gbakima, Brian H Bird, James Bangura, Alexandre Tremeau-Bravard, Manjunatha N Belaganahalli, Heather L Wells, Jasjeet K Dhanota, Eliza Liang, Michael Grodus, Rohit K Jangra, Veronica A DeJesus, Gorka Lasso, Brett R Smith, Amara Jambai, Brima O Kamara, Sorie Kamara, William Bangura, Corina Monagin, Sagi Shapira, Christine K Johnson, Karen Saylors, Edward M Rubin, Kartik Chandran, W Ian Lipkin, Jonna A K Mazet
In the version of this Article originally published, the bat species for 12 individuals were incorrectly identified in Supplementary Table 1 and 2. After resequencing the MT-CytB and MT-CO1 segments and reviewing the data, the authors have corrected the errors for these 12 animals. In the amended version of the Supplementary Information, Supplementary Tables 1 and 2 have been replaced to include the corrected host species information. None of the 12 bats affected were positive for the Bombali virus, and the conclusions of the study are therefore unchanged...
November 8, 2018: Nature Microbiology
Kazuyuki Kasahara, Kimberly A Krautkramer, Elin Org, Kymberleigh A Romano, Robert L Kerby, Eugenio I Vivas, Margarete Mehrabian, John M Denu, Fredrik Bäckhed, Aldons J Lusis, Federico E Rey
Humans with metabolic and inflammatory diseases frequently harbour lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Here we show that a prominent gut-associated butyrate-producing bacterial genus (Roseburia) is inversely correlated with atherosclerotic lesion development in a genetically diverse mouse population. We use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary plant polysaccharides to: impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization; lower systemic inflammation; and ameliorate atherosclerosis...
November 5, 2018: Nature Microbiology
Ahsen Özcan, Patrick Pausch, Andreas Linden, Alexander Wulf, Karola Schühle, Johann Heider, Henning Urlaub, Thomas Heimerl, Gert Bange, Lennart Randau
Type IV CRISPR-Cas modules belong to class 1 prokaryotic adaptive immune systems, which are defined by the presence of multisubunit effector complexes. They usually lack the known Cas proteins involved in adaptation and target cleavage, and their function has not been experimentally addressed. To investigate RNA and protein components of this CRISPR-Cas type, we located a complete type IV cas gene locus and an adjacent CRISPR array on a megaplasmid of Aromatoleum aromaticum EbN1, which contains an additional type I-C system on its chromosome...
November 5, 2018: Nature Microbiology
Jackson W Sorensen, Taylor K Dunivin, Tammy C Tobin, Ashley Shade
Small bacterial and archaeal genomes provide insights into the minimal requirements for life1 and are phylogenetically widespread2 . However, the precise environmental pressures that constrain genome size in free-living microorganisms are unknown. A study including isolates has shown that thermophiles and other bacteria with high optimum growth temperatures often have small genomes3 . It is unclear whether this relationship extends generally to microorganisms in nature4,5 and more specifically to microorganisms that inhabit complex and highly variable environments, such as soils3,6,7 ...
November 5, 2018: Nature Microbiology
Qingbing Zheng, Rui Zhu, Longfa Xu, Maozhou He, Xiaodong Yan, Dongxiao Liu, Zhichao Yin, Yangtao Wu, Yongchao Li, Lisheng Yang, Wangheng Hou, Shuxuan Li, Zizhen Li, Zhenqin Chen, Zhihai Li, Hai Yu, Ying Gu, Jun Zhang, Timothy S Baker, Z Hong Zhou, Barney S Graham, Tong Cheng, Shaowei Li, Ningshao Xia
Enterovirus D68 (EV-D68) undergoes structural transformation between mature, cell-entry intermediate (A-particle) and empty forms throughout its life cycle. Structural information for the various forms and antibody-bound capsids will facilitate the development of effective vaccines and therapeutics against EV-D68 infection, which causes childhood respiratory and paralytic diseases worldwide. Here, we report the structures of three EV-D68 capsid states representing the virus at major phases. We further describe two original monoclonal antibodies (15C5 and 11G1) with distinct structurally defined mechanisms for virus neutralization...
November 5, 2018: Nature Microbiology
Jonathan N Pruneda, Robert J Bastidas, Erithelgi Bertsoulaki, Kirby N Swatek, Balaji Santhanam, Michael J Clague, Raphael H Valdivia, Sylvie Urbé, David Komander
Pathogenic bacteria are armed with potent effector proteins that subvert host signalling processes during infection1 . The activities of bacterial effectors and their associated roles within the host cell are often poorly understood, particularly for Chlamydia trachomatis2 , a World Health Organization designated neglected disease pathogen. We identify and explain remarkable dual Lys63-deubiquitinase (DUB) and Lys-acetyltransferase activities in the Chlamydia effector ChlaDUB1. Crystal structures capturing intermediate stages of each reaction reveal how the same catalytic centre of ChlaDUB1 can facilitate such distinct processes, and enable the generation of mutations that uncouple the two activities...
November 5, 2018: Nature Microbiology
Juan A Mondotte, Valérie Gausson, Lionel Frangeul, Hervé Blanc, Louis Lambrechts, Maria-Carla Saleh
Immune responses in insects are differentially triggered depending on the infection route used by the pathogen. In most studies involving Drosophila melanogaster and viruses, infection is done by injection, while oral infection, which is probably the most common route of viral entry in nature, remains unexplored. Here, we orally infected adults and larvae from wild-type and RNA interference (RNAi) mutant flies with different RNA viruses. We found that, in contrast with what is observed following virus injection, oral infections initiated at larval or adult stages are cleared in adult flies...
October 29, 2018: Nature Microbiology
Roenick P Olmo, Alvaro G A Ferreira, Tatiane C Izidoro-Toledo, Eric R G R Aguiar, Isaque J S de Faria, Kátia P R de Souza, Kátia P Osório, Lauriane Kuhn, Philippe Hammann, Elisa G de Andrade, Yaovi Mathias Todjro, Marcele N Rocha, Thiago H J F Leite, Siad C G Amadou, Juliana N Armache, Simona Paro, Caroline D de Oliveira, Fabiano D Carvalho, Luciano A Moreira, Eric Marois, Jean-Luc Imler, João T Marques
Dengue virus (DENV) is an arbovirus transmitted to humans by Aedes mosquitoes1 . In the insect vector, the small interfering RNA (siRNA) pathway is an important antiviral mechanism against DENV2-5 . However, it remains unclear when and where the siRNA pathway acts during the virus cycle. Here, we show that the siRNA pathway fails to efficiently silence DENV in the midgut of Aedes aegypti although it is essential to restrict systemic replication. Accumulation of DENV-derived siRNAs in the midgut reveals that impaired silencing results from a defect downstream of small RNA biogenesis...
October 29, 2018: Nature Microbiology
Aspen T Reese, Fátima C Pereira, Arno Schintlmeister, David Berry, Michael Wagner, Laura P Hale, Anchi Wu, Sharon Jiang, Heather K Durand, Xiyou Zhou, Richard T Premont, Anna Mae Diehl, Thomas M O'Connell, Susan C Alberts, Tyler R Kartzinel, Robert M Pringle, Robert R Dunn, Justin P Wright, Lawrence A David
Resource limitation is a fundamental factor governing the composition and function of ecological communities. However, the role of resource supply in structuring the intestinal microbiome has not been established and represents a challenge for mammals that rely on microbial symbionts for digestion: too little supply might starve the microbiome while too much might starve the host. We present evidence that microbiota occupy a habitat that is limited in total nitrogen supply within the large intestines of 30 mammal species...
October 29, 2018: Nature Microbiology
Germán G Sgro, Tiago R D Costa, William Cenens, Diorge P Souza, Alexandre Cassago, Luciana Coutinho de Oliveira, Roberto K Salinas, Rodrigo V Portugal, Chuck S Farah, Gabriel Waksman
Type IV secretion (T4S) systems form the most common and versatile class of secretion systems in bacteria, capable of injecting both proteins and DNAs into host cells. T4S systems are typically composed of 12 components that form 2 major assemblies: the inner membrane complex embedded in the inner membrane and the core complex embedded in both the inner and outer membranes. Here we present the 3.3 Å-resolution cryo-electron microscopy model of the T4S system core complex from Xanthomonas citri, a phytopathogen that utilizes this system to kill bacterial competitors...
October 22, 2018: Nature Microbiology
Yassine Cherrak, Chiara Rapisarda, Riccardo Pellarin, Guillaume Bouvier, Benjamin Bardiaux, Fabrice Allain, Christian Malosse, Martial Rey, Julia Chamot-Rooke, Eric Cascales, Rémi Fronzes, Eric Durand
To support their growth in a competitive environment and cause pathogenesis, bacteria have evolved a broad repertoire of macromolecular machineries to deliver specific effectors and toxins. Among these multiprotein complexes, the type VI secretion system (T6SS) is a contractile nanomachine that targets both prokaryotic and eukaryotic cells. The T6SS comprises two functional subcomplexes: a bacteriophage-related tail structure anchored to the cell envelope by a membrane complex. As in other contractile injection systems, the tail is composed of an inner tube wrapped by a sheath and built on the baseplate...
October 15, 2018: Nature Microbiology
D Russ, R Kishony
From natural ecology1-4 to clinical therapy5-8 , cells are often exposed to mixtures of multiple drugs. Two competing null models are used to predict the combined effect of drugs: response additivity (Bliss) and dosage additivity (Loewe)9-11 . Here, noting that these models diverge with increased number of drugs, we contrast their predictions with growth measurements of four phylogenetically distant microorganisms including Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Saccharomyces cerevisiae, under combinations of up to ten different drugs...
October 15, 2018: Nature Microbiology
Steven R Ahrendt, C Alisha Quandt, Doina Ciobanu, Alicia Clum, Asaf Salamov, Bill Andreopoulos, Jan-Fang Cheng, Tanja Woyke, Adrian Pelin, Bernard Henrissat, Nicole K Reynolds, Gerald L Benny, Matthew E Smith, Timothy Y James, Igor V Grigoriev
Environmental DNA surveys reveal that most fungal diversity represents uncultured species. We sequenced the genomes of eight uncultured species across the fungal tree of life using a new single-cell genomics pipeline. We show that, despite a large variation in genome and gene space recovery from each single amplified genome (SAG), ≥90% can be recovered by combining multiple SAGs. SAGs provide robust placement for early-diverging lineages and infer a diploid ancestor of fungi. Early-diverging fungi share metabolic deficiencies and show unique gene expansions correlated with parasitism and unculturability...
October 8, 2018: Nature Microbiology
Anna Dragoš, Marivic Martin, Carolina Falcón Garcia, Lara Kricks, Patrick Pausch, Thomas Heimerl, Balázs Bálint, Gergely Maróti, Gert Bange, Daniel López, Oliver Lieleg, Ákos T Kovács
Closely related microorganisms often cooperate, but the prevalence and stability of cooperation between different genotypes remain debatable. Here, we track the evolution of pellicle biofilms formed through genetic division of labour and ask whether partially deficient partners can evolve autonomy. Pellicles of Bacillus subtilis rely on an extracellular matrix composed of exopolysaccharide (EPS) and the fibre protein TasA. In monocultures, ∆eps and ∆tasA mutants fail to form pellicles, but, facilitated by cooperation, they succeed in co-culture...
October 8, 2018: Nature Microbiology
Leonid Yurkovetskiy, Mehmet Hakan Guney, Kyusik Kim, Shih Lin Goh, Sean McCauley, Ann Dauphin, William E Diehl, Jeremy Luban
Host factors that silence provirus transcription in CD4+ memory T cells help HIV-1 escape eradication by the host immune system and by antiviral drugs1 . These same factors, however, must be overcome for HIV-1 to propagate. Here we show that Vpx and Vpr encoded by diverse primate immunodeficiency viruses activate provirus transcription. Vpx and Vpr are adaptor proteins for the DCAF1-CUL4A/B E3 ubiquitin ligase that degrade SAMHD1 and increase reverse transcription2-4 . Nonetheless, Vpx and Vpr have effects on reporter gene expression that are not explained by SAMHD1 degradation5-8 ...
October 8, 2018: Nature Microbiology
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