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Nadège Bossuet-Greif, Julien Vignard, Frédéric Taieb, Gladys Mirey, Damien Dubois, Claude Petit, Eric Oswald, Jean-Philippe Nougayrède
Colibactins are hybrid polyketide-nonribosomal peptides produced by Escherichia coli , Klebsiella pneumoniae , and other Enterobacteriaceae harboring the pks genomic island. These genotoxic metabolites are produced by pks -encoded peptide-polyketide synthases as inactive prodrugs called precolibactins, which are then converted to colibactins by deacylation for DNA-damaging effects. Colibactins are bona fide virulence factors and are suspected of promoting colorectal carcinogenesis when produced by intestinal E...
March 20, 2018: MBio
Sotaro Chiba, Atif Jamal, Nobuhiro Suzuki
In contrast to well-established internal ribosomal entry site (IRES)-mediated translational initiation in animals and plants, no IRESs were established in fungal viral or cellular RNAs. To identify IRES elements in mycoviruses, we developed a luciferase-based dual-reporter detection system in Cryphonectria parasitica , a model filamentous fungus for virus-host interactions. A bicistronic construct entails a codon-optimized Renilla and firefly luciferase ( ORluc and OFluc , respectively) gene, between which potential IRES sequences can be inserted...
March 20, 2018: MBio
XiaoLi Bing, Joseph Gerlach, Gregory Loeb, Nicolas Buchon
Drosophila suzukii Matsumura is an invasive species of vinegar fly that has become a prominent pest of berries and other soft-skinned fruits. Unlike most other Drosophila species, female D. suzukii flies lay their eggs in ripening and ripe fruits and larvae develop within the fruit. To understand how D. suzukii larvae utilize ripe and ripening fruits, which usually have low levels of protein, we investigated the microbiota of field-captured and laboratory-reared D. suzukii flies and further examined the combined influence of diet and microbes on host fitness...
March 20, 2018: MBio
Maarten G K Ghequire, Toon Swings, Jan Michiels, Susan K Buchanan, René De Mot
Lectin-like bacteriocins (LlpAs) are secreted by proteobacteria and selectively kill strains of their own or related species, and they are composed of two B-lectin domains with divergent sequences. In Pseudomonas spp., initial binding of these antibacterial proteins to cells is mediated by the carboxy-terminal domain through d-rhamnose residues present in the common polysaccharide antigen of their lipopolysaccharide, whereas the amino-terminal domain accounts for strain selectivity of killing. Here, we show that spontaneous LlpA-resistant mutants carry mutations in one of three surface-exposed moieties of the essential β-barrel outer membrane protein insertase BamA, the core component of the BAM complex...
March 20, 2018: MBio
Jason W Shapiro, Catherine Putonti
Bacteriophages are the most abundant and diverse biological entities on the planet, and new phage genomes are being discovered at a rapid pace. As more phage genomes are published, new methods are needed for placing these genomes in an ecological and evolutionary context. Phages are difficult to study by phylogenetic methods, because they exchange genes regularly, and no single gene is conserved across all phages. Here, we demonstrate how gene-level networks can provide a high-resolution view of phage genetic diversity and offer a novel perspective on virus ecology...
March 20, 2018: MBio
Myron M Levine, Raphael Simon
Klemm et al. (mBio 9:e00105-18, 2018, present comprehensive antibiotic sensitivity patterns and genomic sequence data on Salmonella enterica serovar Typhi blood culture isolates from typhoid fever cases during an epidemic in Pakistan. Microbiologic and genomic data pinpoint the identities and locations of the antimicrobial resistance genes and the outbreak strain's lineage. They propose that Salmonella enterica serovar Typhi be added to the list of bacterial pathogens of public health importance that have become extensively drug resistant (XDR)...
March 20, 2018: MBio
John H-O Pettersson, Vegard Eldholm, Stephen J Seligman, Åke Lundkvist, Andrew K Falconar, Michael W Gaunt, Didier Musso, Antoine Nougairède, Remi Charrel, Ernest A Gould, Xavier de Lamballerie
No abstract text is available yet for this article.
March 20, 2018: MBio
Kerrie L May, Thomas J Silhavy
The outer membrane (OM) bilayer of Gram-negative bacteria is biologically unique in its asymmetrical organization of lipids, with an inner leaflet composed of glycerophospholipids (PLs) and a surface-exposed outer leaflet composed of lipopolysaccharide (LPS). This lipid organization is integral to the OM's barrier properties. Perturbations of the outer leaflet by antimicrobial peptides or defects in LPS biosynthesis or transport to the OM cause a compensatory flipping of PLs to the outer leaflet. As a result, lipid asymmetry is disrupted and OM integrity is compromised...
March 20, 2018: MBio
Jonathan Richard, Jérémie Prévost, Amy E Baxter, Benjamin von Bredow, Shilei Ding, Halima Medjahed, Gloria G Delgado, Nathalie Brassard, Christina M Stürzel, Frank Kirchhoff, Beatrice H Hahn, Matthew S Parsons, Daniel E Kaufmann, David T Evans, Andrés Finzi
The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs)...
March 20, 2018: MBio
Lauren D Aarreberg, Courtney Wilkins, Hilario J Ramos, Richard Green, Michael A Davis, Kwan Chow, Michael Gale
Induction of interferon beta (IFN-β), IFN-stimulated genes (ISGs), and inflammatory responses is critical for control of viral infection. We recently identified an essential linkage of stimulation of the inflammatory cytokine interleukin-1β (IL-1β) and induction of ISGs that function as host restriction pathways against the emerging flavivirus West Nile virus (WNV) in vivo Here we utilized ex vivo global transcriptome analysis of primary dendritic cells, known targets of WNV replication, to define gene signatures required for this IL-1β-driven antiviral response...
March 20, 2018: MBio
Joseph M Varberg, Isabelle Coppens, Gustavo Arrizabalaga, Rajshekhar Y Gaji
In the protozoan parasite Toxoplasma gondii , protein kinases have been shown to play key roles in regulating parasite motility, invasion, replication, egress, and survival within the host. The tyrosine kinase-like (TKL) family of proteins are an unexplored set of kinases in Toxoplasma Of the eight annotated TKLs in the Toxoplasma genome, a recent genome-wide loss-of-function screen showed that six are important for tachyzoite fitness. By utilizing an endogenous tagging approach, we showed that these six T...
March 20, 2018: MBio
Florent Masson, Sandra Calderon Copete, Fanny Schüpfer, Gonzalo Garcia-Arraez, Bruno Lemaitre
Endosymbiotic bacteria associated with eukaryotic hosts are omnipresent in nature, particularly in insects. Studying the bacterial side of host-symbiont interactions is, however, often limited by the unculturability and genetic intractability of the symbionts. Spiroplasma poulsonii is a maternally transmitted bacterial endosymbiont that is naturally associated with several Drosophila species. S. poulsonii strongly affects its host's physiology, for example by causing male killing or by protecting it against various parasites...
March 20, 2018: MBio
Amy N Jacobson, Biswa P Choudhury, Michael A Fischbach
Lipopolysaccharide (LPS), a cell-associated glycolipid that makes up the outer leaflet of the outer membrane of Gram-negative bacteria, is a canonical mediator of microbe-host interactions. The most prevalent Gram-negative gut bacterial taxon, Bacteroides , makes up around 50% of the cells in a typical Western gut; these cells harbor ~300 mg of LPS, making it one of the highest-abundance molecules in the intestine. As a starting point for understanding the biological function of Bacteroides LPS, we have identified genes in Bacteroides thetaiotaomicron VPI 5482 involved in the biosynthesis of its lipid A core and glycan, generated mutants that elaborate altered forms of LPS, and used matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry to interrogate the molecular features of these variants...
March 13, 2018: MBio
Fei Xiao, Stanley Wang, Rina Barouch-Bentov, Gregory Neveu, Szuyuan Pu, Melanie Beer, Stanford Schor, Sathish Kumar, Vlad Nicolaescu, Brett D Lindenbach, Glenn Randall, Shirit Einav
Hepatitis C virus (HCV) spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs) AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting. We reported that AP-1A mediates HCV trafficking during release, whereas the endocytic adaptor AP-2 mediates entry and assembly...
March 13, 2018: MBio
Adam J Pelzek, Bo Shopsin, Emily E Radke, Kayan Tam, Beatrix M Ueberheide, David Fenyö, Stuart M Brown, Qianhao Li, Ada Rubin, Yi Fulmer, William K Chiang, David N Hernandez, Hanane El Bannoudi, William E Sause, Alexis Sommerfield, Isaac P Thomsen, Andy O Miller, Victor J Torres, Gregg J Silverman
Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although S. aureus possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and S...
March 13, 2018: MBio
Matthew K Doherty, Tao Ding, Charlie Koumpouras, Shannon E Telesco, Calixte Monast, Anuk Das, Carrie Brodmerkel, Patrick D Schloss
The fecal microbiota is a rich source of biomarkers that have previously been shown to be predictive of numerous disease states. Less well studied is the effect of immunomodulatory therapy on the microbiota and its role in response to therapy. This study explored associations between the fecal microbiota and therapeutic response of Crohn's disease (CD) patients treated with ustekinumab (UST; Stelara) in the phase 2 CERTIFI study. Using stool samples collected over the course of 22 weeks, the composition of these subjects' fecal bacterial communities was characterized by sequencing the 16S rRNA gene...
March 13, 2018: MBio
Karissa L Cross, Payal Chirania, Weili Xiong, Clifford J Beall, James G Elkins, Richard J Giannone, Ann L Griffen, Adam M Guss, Robert L Hettich, Snehal S Joshi, Elaine M Mokrzan, Roman K Martin, Igor B Zhulin, Eugene J Leys, Mircea Podar
The human oral microbiota encompasses representatives of many bacterial lineages that have not yet been cultured. Here we describe the isolation and characterization of previously uncultured Desulfobulbus oralis , the first human-associated representative of its genus. As mammalian-associated microbes rarely have free-living close relatives, D. oralis provides opportunities to study how bacteria adapt and evolve within a host. This sulfate-reducing deltaproteobacterium has adapted to the human oral subgingival niche by curtailing its physiological repertoire, losing some biosynthetic abilities and metabolic independence, and by dramatically reducing environmental sensing and signaling capabilities...
March 13, 2018: MBio
Johannes G Rebelein, Chi Chung Lee, Megan Newcomb, Yilin Hu, Markus W Ribbe
The Mo- and V-nitrogenases are two homologous members of the nitrogenase family that are distinguished mainly by the presence of different heterometals (Mo or V) at their respective cofactor sites (M- or V-cluster). However, the V-nitrogenase is ~600-fold more active than its Mo counterpart in reducing CO to hydrocarbons at ambient conditions. Here, we expressed an M-cluster-containing, hybrid V-nitrogenase in Azotobacter vinelandii and compared it to its native, V-cluster-containing counterpart in order to assess the impact of protein scaffold and cofactor species on the differential reactivities of Mo- and V-nitrogenases toward CO...
March 13, 2018: MBio
Scott D Kobayashi, Adeline R Porter, Brett Freedman, Ruchi Pandey, Liang Chen, Barry N Kreiswirth, Frank R DeLeo
Carbapenem-resistant Klebsiella pneumoniae is a problem worldwide. A carbapenem-resistant K. pneumoniae lineage classified as multilocus sequence type 258 (ST258) is prominent in the health care setting in many regions of the world, including the United States. ST258 strains can be resistant to virtually all clinically useful antibiotics; treatment of infections caused by these organisms is difficult, and mortality is high. As a step toward promoting development of new therapeutics for ST258 infections, we tested the ability of rabbit antibodies specific for ST258 capsule polysaccharide to enhance human serum bactericidal activity and promote phagocytosis and killing of these bacteria by human neutrophils...
March 13, 2018: MBio
M Georgieva, L Kagedan, Ying-Jie Lu, C M Thompson, M Lipsitch
Genomic analysis reveals extensive sequence variation and hot spots of recombination in surface proteins of Streptococcus pneumoniae While this phenomenon is commonly attributed to diversifying selection by host immune responses, there is little mechanistic evidence for the hypothesis that diversification of surface protein antigens produces an immune escape benefit during infection with S. pneumoniae Here, we investigate the biological significance of sequence variation within the S. pneumoniae cell wall-associated pneumococcal surface protein C (PspC) protein antigen...
March 13, 2018: MBio
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