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Archive

November/December 2019; Volume 10,Issue 6

Commentary

  • Influenza’s Newest Trick
    Commentary | Host-Microbe Biology
    Influenza’s Newest Trick

    Influenza A viruses are important pathogens for humans and for many birds and mammals. Hemagglutinin and neuraminidase are the major surface proteins of this enveloped RNA virus.

    Jeffery K. Taubenberger
    10 Dec 2019

Observation

  • Cell Cycle-Dependent Flagellar Disassembly in a Firebug Trypanosomatid <em>Leptomonas pyrrhocoris</em>
    Observation | Molecular Biology and Physiology
    Cell Cycle-Dependent Flagellar Disassembly in a Firebug Trypanosomatid Leptomonas pyrrhocoris

    Current understanding of flagellum biogenesis during the cell cycle in trypanosomatids is limited to a few pathogenic species, including Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. The most notable characteristics of trypanosomatid flagella studied so far are the extreme...

    Cynthia Y. He, Adarsh Singh, Vyacheslav Yurchenko
    26 Nov 2019

Research Article

  • Intestinal IgA Regulates Expression of a Fructan Polysaccharide Utilization Locus in Colonizing Gut Commensal <span class="named-content genus-species" id="named-content-1">Bacteroides thetaiotaomicron</span>
    Research Article | Host-Microbe Biology
    Intestinal IgA Regulates Expression of a Fructan Polysaccharide Utilization Locus in Colonizing Gut Commensal Bacteroides thetaiotaomicron

    Given the significant impact that gut microbes have on our health, it is essential to identify key host and environmental factors that shape this diverse community. While many studies have highlighted the impact of diet on gut microbiota, little is known about how the host regulates this critical diet-microbiota interaction. In our present study, we discovered that gut IgA targeted a protein complex involved in the utilization of an...

    Payal Joglekar, Hua Ding, Pablo Canales-Herrerias, Pankaj Jay Pasricha, Justin L. Sonnenburg, Daniel A. Peterson
    5 Nov 2019
  • DNA- and RNA-SIP Reveal <em>Nitrospira</em> spp. as Key Drivers of Nitrification in Groundwater-Fed Biofilters
    Research Article | Applied and Environmental Science
    DNA- and RNA-SIP Reveal Nitrospira spp. as Key Drivers of Nitrification in Groundwater-Fed Biofilters

    With this study we provide the first in situ evidence of ecologically relevant ammonia oxidation by comammox Nitrospira in a complex microbiome and document an unexpectedly high H13CO3− uptake and growth of proteobacterial and acidobacterial taxa under ammonia selectivity. This finding raises the question of whether comammox Nitrospira is an equally important ammonia oxidizer...

    Arda Gülay, S. Jane Fowler, Karolina Tatari, Bo Thamdrup, Hans-Jørgen Albrechtsen, Waleed Abu Al-Soud, Søren J. Sørensen, Barth F. Smets
    5 Nov 2019
  • A Novel Neuraminidase-Dependent Hemagglutinin Cleavage Mechanism Enables the Systemic Spread of an H7N6 Avian Influenza Virus
    Editor's Pick Research Article | Host-Microbe Biology
    A Novel Neuraminidase-Dependent Hemagglutinin Cleavage Mechanism Enables the Systemic Spread of an H7N6 Avian Influenza Virus

    The identification of virulence markers in influenza viruses underpins risk assessment programs and the development of novel therapeutics. The cleavage of the influenza virus HA is a required step in the viral life cycle, and phenotypic differences in viruses can be caused by changes in this process. Here, we describe a novel mechanism for HA cleavage in an H7N6 influenza virus isolated from a mallard duck. The mechanism requires the N6...

    Hyeok-il Kwon, Young-Il Kim, Su-Jin Park, Eun-Ha Kim, Semi Kim, Young-Jae Si, Min-Suk Song, Philippe Noriel Q. Pascua, Elena A. Govorkova, Robert G. Webster, Richard J. Webby, Young Ki Choi
    5 Nov 2019
  • Cause and Effectors: Whole-Genome Comparisons Reveal Shared but Rapidly Evolving Effector Sets among Host-Specific Plant-Castrating Fungi
    Research Article | Host-Microbe Biology
    Cause and Effectors: Whole-Genome Comparisons Reveal Shared but Rapidly Evolving Effector Sets among Host-Specific Plant-Castrating Fungi

    Plant pathogens use molecular weapons to successfully infect their hosts, secreting a large portfolio of various proteins and enzymes. Different plant species are often parasitized by host-specific pathogens; however, it is still unclear whether the molecular basis of such host specialization involves species-specific weapons or different variants of the same weapons. We therefore compared the genes encoding secreted proteins in three...

    William C. Beckerson, Ricardo C. Rodríguez de la Vega, Fanny E. Hartmann, Marine Duhamel, Tatiana Giraud, Michael H. Perlin
    5 Nov 2019
  • Analysis of CA Content and CPSF6 Dependence of Early HIV-1 Replication Complexes in SupT1-R5 Cells
    Research Article | Host-Microbe Biology
    Analysis of CA Content and CPSF6 Dependence of Early HIV-1 Replication Complexes in SupT1-R5 Cells

    The HIV-1 capsid performs essential functions during early viral replication and is an interesting target for novel antivirals. Thus, understanding molecular and structural details of capsid function will be important for elucidating early HIV-1 (and retroviral in general) replication in relevant target cells and may also aid antiviral development. Here, we show that HIV-1 capsids stay largely intact during transport to the nucleus of...

    Vojtech Zila, Thorsten G. Müller, Vibor Laketa, Barbara Müller, Hans-Georg Kräusslich
    5 Nov 2019
  • Paternal Grandmother Age Affects the Strength of <em>Wolbachia</em>-Induced Cytoplasmic Incompatibility in <span class="named-content genus-species" id="named-content-1">Drosophila melanogaster</span>
    Research Article | Host-Microbe Biology
    Paternal Grandmother Age Affects the Strength of Wolbachia-Induced Cytoplasmic Incompatibility in Drosophila melanogaster

    Unidirectional cytoplasmic incompatibility (CI) results in a postfertilization incompatibility between Wolbachia-infected males and uninfected females. CI contributes to reproductive isolation between closely related species and is used in worldwide vector control programs to drastically lower arboviral vector population sizes or to replace populations that transmit arboviruses with those resistant to transmission. Despite...

    Emily M. Layton, Jungmin On, Jessamyn I. Perlmutter, Seth R. Bordenstein, J. Dylan Shropshire
    5 Nov 2019
  • Preclinical Efficacy of a Lipooligosaccharide Peptide Mimic Candidate Gonococcal Vaccine
    Research Article | Therapeutics and Prevention
    Preclinical Efficacy of a Lipooligosaccharide Peptide Mimic Candidate Gonococcal Vaccine

    Neisseria gonorrhoeae has become resistant to most antibiotics. The incidence of gonorrhea is also sharply increasing. A safe and effective antigonococcal vaccine is urgently needed. Lipooligosaccharide (LOS), the most abundant outer membrane molecule, is indispensable for gonococcal pathogenesis. A glycan epitope on LOS that is recognized by monoclonal antibody (MAb...

    Sunita Gulati, Michael W. Pennington, Andrzej Czerwinski, Darrick Carter, Bo Zheng, Nancy A. Nowak, Rosane B. DeOliveira, Jutamas Shaughnessy, George W. Reed, Sanjay Ram, Peter A. Rice
    5 Nov 2019
  • Drug-Resistant Epimutants Exhibit Organ-Specific Stability and Induction during Murine Infections Caused by the Human Fungal Pathogen <span class="named-content genus-species" id="named-content-1">Mucor circinelloides</span>
    Research Article | Host-Microbe Biology
    Drug-Resistant Epimutants Exhibit Organ-Specific Stability and Induction during Murine Infections Caused by the Human Fungal Pathogen Mucor circinelloides

    The emerging fungal pathogen Mucor circinelloides causes a severe infection, mucormycosis, which leads to considerable morbidity and mortality. Treatment of Mucor infection is challenging because Mucor is inherently resistant to nearly all clinical antifungal agents. An RNAi-dependent and reversible mechanism of antifungal resistance, epimutation,...

    Zanetta Chang, Joseph Heitman
    5 Nov 2019
  • Photoferrotrophs Produce a PioAB Electron Conduit for Extracellular Electron Uptake
    Research Article | Applied and Environmental Science
    Photoferrotrophs Produce a PioAB Electron Conduit for Extracellular Electron Uptake

    Some anoxygenic phototrophs use soluble iron, insoluble iron minerals (such as rust), or their proxies (poised electrodes) as electron donors for photosynthesis. However, the underlying electron uptake mechanisms are not well established. Here, we show that these phototrophs use a protein complex made of an outer membrane porin and a periplasmic decaheme cytochrome (electron transfer protein) to harvest electrons from both soluble iron...

    Dinesh Gupta, Molly C. Sutherland, Karthikeyan Rengasamy, J. Mark Meacham, Robert G. Kranz, Arpita Bose
    5 Nov 2019
  • <span class="named-content genus-species" id="named-content-1">Candida albicans</span> <em>rvs161</em>Δ and <em>rvs167</em>Δ Endocytosis Mutants Are Defective in Invasion into the Oral Cavity
    Research Article | Host-Microbe Biology
    Candida albicans rvs161Δ and rvs167Δ Endocytosis Mutants Are Defective in Invasion into the Oral Cavity

    Oropharyngeal candidiasis (OPC) is a common fungal infection that is associated with severe morbidity. Another concern is that patients at risk for developing OPC often take long courses of antifungal drugs, which can lead to the emergence of drug-resistant C. albicans strains. We therefore identified nine mutants with defects in undergoing invasive hyphal growth in...

    Shamoon Naseem, Lois M. Douglas, James B. Konopka
    12 Nov 2019
  • High-Risk International Clones of Carbapenem-Nonsusceptible <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span> Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level
    Research Article | Clinical Science and Epidemiology
    High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level

    In low-to-middle-income countries such as Indonesia, work in intensive care units (ICUs) can be hampered by lack of resources. Conducting large epidemiological studies in such settings using genomic tools is rather challenging. Still, we were able to systematically study the transmissions of carbapenem-nonsusceptible strains of P. aeruginosa (CNPA) within and between...

    Andreu Coello Pelegrin, Yulia Rosa Saharman, Aurélien Griffon, Mattia Palmieri, Caroline Mirande, Anis Karuniawati, Rudyanto Sedono, Dita Aditianingsih, Wil H. F. Goessens, Alex van Belkum, Henri A. Verbrugh, Corné H. W. Klaassen, Juliëtte A. Severin
    12 Nov 2019
  • Unusual Metabolism and Hypervariation in the Genome of a Gracilibacterium (BD1-5) from an Oil-Degrading Community
    Research Article | Applied and Environmental Science
    Unusual Metabolism and Hypervariation in the Genome of a Gracilibacterium (BD1-5) from an Oil-Degrading Community

    CPR bacteria are generally predicted to be symbionts due to their extensive biosynthetic deficits. Although monophyletic, they are not monolithic in terms of their lifestyles. The organism described here appears to have evolved an unusual metabolic platform not reliant on glucose or pentose sugars. Its biology appears to be centered around bacterial host-derived compounds and/or cell detritus. Amino acids likely provide building blocks...

    Christian M. K. Sieber, Blair G. Paul, Cindy J. Castelle, Ping Hu, Susannah G. Tringe, David L. Valentine, Gary L. Andersen, Jillian F. Banfield
    12 Nov 2019
  • Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen <span class="named-content genus-species" id="named-content-1">Cryptococcus neoformans</span>
    Research Article | Host-Microbe Biology
    Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen Cryptococcus neoformans

    Fungal survival in a mammalian host requires the coordinated expression and downregulation of a large cohort of genes in response to cellular stresses. Initial infection with C. neoformans occurs in the lungs, where it interacts with host macrophages. Surviving macrophage-derived cellular stresses, such as the production of reactive oxygen and nitrogen species, is...

    Jay Leipheimer, Amanda L. M. Bloom, Christopher S. Campomizzi, Yana Salei, John C. Panepinto
    12 Nov 2019
  • Diversity in <em>lac</em> Operon Regulation among Diverse <span class="named-content genus-species" id="named-content-1">Escherichia coli</span> Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness
    Research Article | Ecological and Evolutionary Science
    Diversity in lac Operon Regulation among Diverse Escherichia coli Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness

    The lac operon of Escherichia coli is a classic model for studying gene regulation. This study has uncovered features such as the environmental input logic controlling gene expression, as well as gene expression bistability and hysteresis. Most lac operon studies have focused on a few lab strains, and it is not known how generally those findings...

    Kelly N. Phillips, Scott Widmann, Huei-Yi Lai, Jennifer Nguyen, J. Christian J. Ray, Gábor Balázsi, Tim F. Cooper
    12 Nov 2019
  • <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span> Exploits the Host Apoptotic Pathway To Persist during Infection
    Research Article | Host-Microbe Biology
    Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection

    Caspase-3 controls the apoptotic pathway, a form of programmed cell death designed to be immunologically silent. Polymorphisms leading to reduced caspase-3 activity are associated with variable effects on tumorigenesis and yet arise frequently. Staphylococcus aureus is a human commensal and a frequent cause of soft tissue and bloodstream infections. Successful...

    Volker Winstel, Olaf Schneewind, Dominique Missiakas
    12 Nov 2019
  • A New Lineage of <span class="named-content genus-species" id="named-content-1">Cryptococcus gattii</span> (VGV) Discovered in the Central Zambezian Miombo Woodlands
    Research Article | Ecological and Evolutionary Science
    A New Lineage of Cryptococcus gattii (VGV) Discovered in the Central Zambezian Miombo Woodlands

    Cryptococcus gattii is an environmental pathogen that causes severe systemic infection in immunocompetent individuals more often than in immunocompromised humans. Over the past 2 decades, researchers have shown that C. gattii falls within four genetically distinct major lineages. By combining field...

    Rhys A. Farrer, Miwha Chang, Michael J. Davis, Lucy van Dorp, Dong-Hoon Yang, Terrance Shea, Thomas R. Sewell, Wieland Meyer, Francois Balloux, Hannah M. Edwards, Duncan Chanda, Geoffrey Kwenda, Mathieu Vanhove, Yun C. Chang, Christina A. Cuomo, Matthew C. Fisher, Kyung J. Kwon-Chung
    12 Nov 2019
  • Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling
    Research Article | Host-Microbe Biology
    Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling

    Many RNA viruses that are highly pathogenic in humans are relatively apathogenic in their bat reservoirs, making it important to compare innate immune responses in bats to those well characterized in humans. One such antiviral response is the OAS-RNase L pathway. OASs, upon sensing dsRNA, produce 2-5A, leading to activation of RNase L which degrades viral and host RNA, limiting viral replication. Analysis of Egyptian Rousette bat...

    Yize Li, Beihua Dong, Zuzhang Wei, Robert H. Silverman, Susan R. Weiss
    12 Nov 2019
  • TREM-1 Protects HIV-1-Infected Macrophages from Apoptosis through Maintenance of Mitochondrial Function
    Research Article | Molecular Biology and Physiology
    TREM-1 Protects HIV-1-Infected Macrophages from Apoptosis through Maintenance of Mitochondrial Function

    The major challenge to human immunodeficiency virus (HIV) treatment is the development of strategies that lead to viral eradication. A roadblock to accomplishing this goal is the lack of an approach that would safely eliminate HIV from all resting/latent reservoirs, including macrophages. Macrophages are a key part of the innate immune system and are responsible for recognizing invading microbes and sending appropriate signals to other...

    Grant R. Campbell, Rachel K. To, Stephen A. Spector
    12 Nov 2019
  • Transcriptomic Signatures Predict Regulators of Drug Synergy and Clinical Regimen Efficacy against Tuberculosis
    Research Article | Therapeutics and Prevention
    Transcriptomic Signatures Predict Regulators of Drug Synergy and Clinical Regimen Efficacy against Tuberculosis

    Multidrug combination therapy is an important strategy for treating tuberculosis, the world’s deadliest bacterial infection. Long treatment durations and growing rates of drug resistance have created an urgent need for new approaches to prioritize effective drug regimens. Hence, we developed a computational model called INDIGO-MTB that identifies synergistic drug regimens from an immense set of possible drug combinations using the...

    Shuyi Ma, Suraj Jaipalli, Jonah Larkins-Ford, Jenny Lohmiller, Bree B. Aldridge, David R. Sherman, Sriram Chandrasekaran
    12 Nov 2019
  • IRG1 and Inducible Nitric Oxide Synthase Act Redundantly with Other Interferon-Gamma-Induced Factors To Restrict Intracellular Replication of <span class="named-content genus-species" id="named-content-1">Legionella pneumophila</span>
    Research Article | Host-Microbe Biology
    IRG1 and Inducible Nitric Oxide Synthase Act Redundantly with Other Interferon-Gamma-Induced Factors To Restrict Intracellular Replication of Legionella pneumophila

    Legionella pneumophila is one example among many species of pathogenic bacteria that replicate within mammalian macrophages during infection. The immune signaling factor interferon gamma (IFN-γ) blocks L. pneumophila replication in macrophages and is an essential component of the immune response to...

    Jordan V. Price, Daniel Russo, Daisy X. Ji, Roberto A. Chavez, Lucian DiPeso, Angus Yiu-Fai Lee, Jörn Coers, Russell E. Vance
    12 Nov 2019
  • NusG-Dependent RNA Polymerase Pausing and Tylosin-Dependent Ribosome Stalling Are Required for Tylosin Resistance by Inducing 23S rRNA Methylation in <span class="named-content genus-species" id="named-content-1">Bacillus subtilis</span>
    Research Article | Molecular Biology and Physiology
    NusG-Dependent RNA Polymerase Pausing and Tylosin-Dependent Ribosome Stalling Are Required for Tylosin Resistance by Inducing 23S rRNA Methylation in Bacillus subtilis

    Antibiotic resistance is a growing health concern. Resistance mechanisms have evolved that provide bacteria with a growth advantage in their natural habitat such as the soil. We determined that B. subtilis, a Gram-positive soil organism, has a mechanism of resistance to tylosin, a macrolide antibiotic commonly used in the meat industry. Tylosin induces expression of...

    Helen Yakhnin, Alexander V. Yakhnin, Brandon L. Mouery, Zachary F. Mandell, Catherine Karbasiafshar, Mikhail Kashlev, Paul Babitzke
    12 Nov 2019
  • A Single Salt Bridge in VIM-20 Increases Protein Stability and Antibiotic Resistance under Low-Zinc Conditions
    Research Article | Clinical Science and Epidemiology
    A Single Salt Bridge in VIM-20 Increases Protein Stability and Antibiotic Resistance under Low-Zinc Conditions

    Antibiotic resistance is a growing clinical threat. One of the most serious areas of concern is the ability of some bacteria to degrade carbapenems, drugs that are often reserved as last-resort antibiotics. Resistance to carbapenems can be conferred by a large group of related enzymes called metallo-β-lactamases that rely on zinc ions for function and for overall stability. Here, we studied an extensive panel of 45 different metallo-β-...

    Zishuo Cheng, Ben A. Shurina, Christopher R. Bethel, Pei W. Thomas, Steven H. Marshall, Caitlyn A. Thomas, Kundi Yang, Robert L. Kimble, Jonathan S. Montgomery, Matthew G. Orischak, Callie M. Miller, Jordan L. Tennenbaum, Jay C. Nix, David L. Tierney, Walter Fast, Robert A. Bonomo, Richard C. Page, Michael W. Crowder
    19 Nov 2019
  • Changes in Aphid Host Plant Diet Influence the Small-RNA Expression Profiles of Its Obligate Nutritional Symbiont, <em>Buchnera</em>
    Research Article | Host-Microbe Biology
    Changes in Aphid Host Plant Diet Influence the Small-RNA Expression Profiles of Its Obligate Nutritional Symbiont, Buchnera

    In general, the genomes of intracellular bacterial symbionts are reduced compared to those of free-living relatives and lack many key regulatory genes. Many of these reduced genomes belong to obligate mutualists of insects that feed on a diet that is deficient in essential nutrients, such as essential amino acids. It is unclear if these symbionts respond with their host to changes in insect diet, because of their reduced regulatory...

    Margaret W. Thairu, Allison K. Hansen
    19 Nov 2019
  • The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in <span class="named-content genus-species" id="named-content-1">Yersinia pestis</span> during Planktonic Growth and Growth in Biofilms
    Research Article | Host-Microbe Biology
    The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in Yersinia pestis during Planktonic Growth and Growth in Biofilms

    Bacterial pathogens have evolved extensive signaling pathways to translate environmental signals into changes in gene expression. While Crp has long been appreciated for its role in regulating metabolism of carbon sources in many bacterial species, transcriptional profiling has revealed that this protein regulates many other aspects of bacterial physiology. The plague pathogen...

    Jeremy T. Ritzert, George Minasov, Ryan Embry, Matthew J. Schipma, Karla J. F. Satchell
    19 Nov 2019
  • Multidrug Resistance in <span class="named-content genus-species" id="named-content-1">Neisseria gonorrhoeae</span>: Identification of Functionally Important Residues in the MtrD Efflux Protein
    Research Article | Therapeutics and Prevention
    Multidrug Resistance in Neisseria gonorrhoeae: Identification of Functionally Important Residues in the MtrD Efflux Protein

    With over 78 million new infections globally each year, gonorrhea remains a frustratingly common infection. Continuous development and spread of antimicrobial-resistant strains of Neisseria gonorrhoeae, the causative agent of gonorrhea, have posed a serious threat to public health. One of the mechanisms in...

    Mohsen Chitsaz, Lauren Booth, Mitchell T. Blyth, Megan L. O’Mara, Melissa H. Brown
    19 Nov 2019
  • The Immune Protein Calprotectin Impacts <span class="named-content genus-species" id="named-content-1">Clostridioides difficile</span> Metabolism through Zinc Limitation
    Research Article | Host-Microbe Biology
    The Immune Protein Calprotectin Impacts Clostridioides difficile Metabolism through Zinc Limitation

    Clostridioides difficile infection (CDI) is the leading cause of postantibiotic nosocomial infection. Antibiotic therapy can be successful, yet up to one-third of individuals suffer from recurrent infections. Understanding the mechanisms controlling C. difficile colonization is paramount in...

    Christopher A. Lopez, William N. Beavers, Andy Weiss, Reece J. Knippel, Joseph P. Zackular, Walter Chazin, Eric P. Skaar
    19 Nov 2019
  • <span class="named-content genus-species" id="named-content-1">Enterococcus faecalis</span> Enhances Expression and Activity of the Enterohemorrhagic <span class="named-content genus-species" id="named-content-2">Escherichia coli</span> Type III Secretion System
    Research Article | Host-Microbe Biology
    Enterococcus faecalis Enhances Expression and Activity of the Enterohemorrhagic Escherichia coli Type III Secretion System

    This work reveals a complex and multifaceted interaction between a human gut commensal, Enterococcus faecalis, and a pathogen, enterohemorrhagic E. coli. We demonstrate that E. faecalis enhances expression of the enterohemorrhagic...

    Elizabeth A. Cameron, Vanessa Sperandio, Gary M. Dunny
    19 Nov 2019
  • <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span> Leucine Aminopeptidase Influences Early Biofilm Composition and Structure via Vesicle-Associated Antibiofilm Activity
    Research Article | Host-Microbe Biology
    Pseudomonas aeruginosa Leucine Aminopeptidase Influences Early Biofilm Composition and Structure via Vesicle-Associated Antibiofilm Activity

    Biofilm formation by the bacterial pathogen P. aeruginosa is known to contribute to drug resistance in nosocomial infections and chronic lung infections of cystic fibrosis patients. In order to treat these infections more successfully, the mechanisms of bacterial biofilm development must be elucidated. While both bacterially secreted aminopeptidase and outer membrane...

    Caitlin N. Esoda, Meta J. Kuehn
    19 Nov 2019
  • A Fungal Arrestin Protein Contributes to Cell Cycle Progression and Pathogenesis
    Research Article | Host-Microbe Biology
    A Fungal Arrestin Protein Contributes to Cell Cycle Progression and Pathogenesis

    To survive under unpredictable conditions, all organisms must adapt to stressors by regulating adaptive cellular responses. Arrestin proteins are conserved regulators of adaptive cellular responses in eukaryotes. Studies that have been limited to mammals and model fungi have demonstrated that the disruption of arrestin-regulated pathways is detrimental for viability. The human fungal pathogen...

    Calla L. Telzrow, Connie B. Nichols, Natalia Castro-Lopez, Floyd L. Wormley, Jr., J. Andrew Alspaugh
    19 Nov 2019
  • Bacteriophage Adherence to Mucus Mediates Preventive Protection against Pathogenic Bacteria
    Editor's Pick Research Article | Host-Microbe Biology
    Bacteriophage Adherence to Mucus Mediates Preventive Protection against Pathogenic Bacteria

    The mucosal surfaces of animals are habitat for microbes, including viruses. Bacteriophages—viruses that infect bacteria—were shown to be able to bind to mucus. This may result in a symbiotic relationship in which phages find bacterial hosts to infect, protecting the mucus-producing animal from bacterial infections in the process. Here, we studied phage binding on mucus and the effect of mucin on phage-bacterium interactions. The...

    Gabriel M. F. Almeida, Elina Laanto, Roghaieh Ashrafi, Lotta-Riina Sundberg
    19 Nov 2019
  • Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction
    Research Article | Host-Microbe Biology
    Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction

    We demonstrate that HIV-1 uses a common two-step cell-to-cell fusion mechanism for massive virus transfer from infected T lymphocytes and dissemination to myeloid target cells, including dendritic cells and macrophages as well as osteoclasts. This cell-to-cell infection process bypasses the restriction imposed by the SAMHD1 host cell restriction factor for HIV-1 replication, leading to the formation of highly virus-productive...

    Maorong Xie, Héloïse Leroy, Rémi Mascarau, Marie Woottum, Maeva Dupont, Camille Ciccone, Alain Schmitt, Brigitte Raynaud-Messina, Christel Vérollet, Jérôme Bouchet, Lucie Bracq, Serge Benichou
    19 Nov 2019
  • Functional Multigenomic Screening of Human-Associated Bacteria for NF-κB-Inducing Bioactive Effectors
    Research Article | Host-Microbe Biology
    Functional Multigenomic Screening of Human-Associated Bacteria for NF-κB-Inducing Bioactive Effectors

    Human-associated bacteria are thought to encode bioactive small molecules and proteins that play an intimate role in human health and disease. Here, we report on the creation and functional screening of a multigenomic library constructed using genomic DNA from 116 bacteria found at diverse sites across the human body. Individual clones were screened for genes capable of conferring NF-κB-inducing activity to...

    Andreia B. Estrela, Toshiki G. Nakashige, Christophe Lemetre, Ian D. Woodworth, Jazz L. Weisman, Louis J. Cohen, Sean F. Brady
    19 Nov 2019
  • The <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span> Transcriptome during Cystic Fibrosis Lung Infection
    Research Article | Host-Microbe Biology
    The Staphylococcus aureus Transcriptome during Cystic Fibrosis Lung Infection

    Although bacteria have been studied in infection for over 100 years, the majority of these studies have utilized laboratory and animal models that often have unknown relevance to the human infections they are meant to represent. A primary challenge has been to assess bacterial physiology in the human host. To address this challenge, we performed transcriptomics of S. aureus...

    Carolyn B. Ibberson, Marvin Whiteley
    19 Nov 2019
  • Gene Regulation Shifts Shed Light on Fungal Adaption in Plant Biomass Decomposers
    Research Article | Applied and Environmental Science
    Gene Regulation Shifts Shed Light on Fungal Adaption in Plant Biomass Decomposers

    Fungi dominate the turnover of wood, Earth’s largest pool of aboveground terrestrial carbon. Fungi first evolved this capacity by degrading lignin to access and hydrolyze embedded carbohydrates (white rot). Multiple lineages, however, adapted faster reactive oxygen species (ROS) pretreatments to loosen lignocellulose and selectively extract sugars (brown rot). This brown rot “shortcut” often coincided with losses (>60%) of...

    Jiwei Zhang, Kevin A. T. Silverstein, Jesus David Castaño, Melania Figueroa, Jonathan S. Schilling
    19 Nov 2019
  • Population Structure and Genetic Diversity among Isolates of <em>Coccidioides posadasii</em> in Venezuela and Surrounding Regions
    Research Article | Ecological and Evolutionary Science
    Population Structure and Genetic Diversity among Isolates of Coccidioides posadasii in Venezuela and Surrounding Regions

    Valley Fever is a fungal disease caused by two species of fungi: Coccidioides immitis and C. posadasii. These fungi are found throughout the arid regions of North and South America; however, our understanding of genetic diversity and disease in South America is limited. In this report, we analyze 10 new genomes of Coccidioides posadasii from regions...

    Marcus M. Teixeira, Primavera Alvarado, Chandler C. Roe, George R. Thompson, III, José S. L. Patané, Jason W. Sahl, Paul Keim, John N. Galgiani, Anastasia P. Litvintseva, Daniel R. Matute, Bridget M. Barker
    26 Nov 2019
  • Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span> Lineage from the Indian Subcontinent
    Research Article | Clinical Science and Epidemiology
    Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent

    The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in...

    Eike J. Steinig, Sebastian Duchene, D. Ashley Robinson, Stefan Monecke, Maho Yokoyama, Maisem Laabei, Peter Slickers, Patiyan Andersson, Deborah Williamson, Angela Kearns, Richard V. Goering, Elizabeth Dickson, Ralf Ehricht, Margaret Ip, Matthew V. N. O’Sullivan, Geoffrey W. Coombs, Andreas Petersen, Grainne Brennan, Anna C. Shore, David C. Coleman, Annalisa Pantosti, Herminia de Lencastre, Henrik Westh, Nobumichi Kobayashi, Helen Heffernan, Birgit Strommenger, Franziska Layer, Stefan Weber, Hege Vangstein Aamot, Leila Skakni, Sharon J. Peacock, Derek Sarovich, Simon Harris, Julian Parkhill, Ruth C. Massey, Mathew T. G. Holden, Stephen D. Bentley, Steven Y. C. Tong
    26 Nov 2019
  • The Toxin-Antitoxin MazEF Drives <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span> Biofilm Formation, Antibiotic Tolerance, and Chronic Infection
    Research Article | Molecular Biology and Physiology
    The Toxin-Antitoxin MazEF Drives Staphylococcus aureus Biofilm Formation, Antibiotic Tolerance, and Chronic Infection

    Surgical infections are one of the most common types of infections encountered in a hospital. Staphylococcus aureus is the most common pathogen associated with this infection. These infections are resilient and difficult to eradicate, as the bacteria form biofilm, a community of bacteria held together by an extracellular matrix. Compared to bacteria that are...

    Dongzhu Ma, Jonathan B. Mandell, Niles P. Donegan, Ambrose L. Cheung, Wanyan Ma, Scott Rothenberger, Robert M. Q. Shanks, Anthony R. Richardson, Kenneth L. Urish
    26 Nov 2019
  • Measles Virus Ribonucleoprotein Complexes Rapidly Spread across Well-Differentiated Primary Human Airway Epithelial Cells along F-Actin Rings
    Research Article | Molecular Biology and Physiology
    Measles Virus Ribonucleoprotein Complexes Rapidly Spread across Well-Differentiated Primary Human Airway Epithelial Cells along F-Actin Rings

    The ability of viral particles to directly spread cell to cell within the airways without particle release is considered to be highly advantageous to many respiratory viruses. Our previous studies in well-differentiated, primary human airway epithelial cells suggest that measles virus (MeV) spreads cell to cell by eliciting the formation of intercellular membrane pores. Based on a newly generated ribonucleoprotein complex (RNP) “tracker...

    Brajesh K. Singh, Christian K. Pfaller, Roberto Cattaneo, Patrick L. Sinn
    26 Nov 2019
  • A Heat-Killed <em>Cryptococcus</em> Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model
    Research Article | Host-Microbe Biology
    A Heat-Killed Cryptococcus Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model

    Invasive fungal infections kill more than 1.5 million people each year, with limited treatment options. There is no vaccine available in clinical use to prevent and control fungal infections. Our recent studies showed that a mutant of the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase in Cryptococcus neoformans, elicited superior protective Th1 host immunity...

    Yina Wang, Keyi Wang, Jorge A. Masso-Silva, Amariliz Rivera, Chaoyang Xue
    26 Nov 2019
  • Mycobacterial OtsA Structures Unveil Substrate Preference Mechanism and Allosteric Regulation by 2-Oxoglutarate and 2-Phosphoglycerate
    Research Article | Molecular Biology and Physiology
    Mycobacterial OtsA Structures Unveil Substrate Preference Mechanism and Allosteric Regulation by 2-Oxoglutarate and 2-Phosphoglycerate

    Mycobacterial infections are a significant source of mortality worldwide, causing millions of deaths annually. Trehalose is a multipurpose disaccharide that plays a fundamental structural role in these organisms as a component of mycolic acids, a molecular hallmark of the cell envelope of mycobacteria. Here, we describe the first mycobacterial OtsA structures. We show mechanisms of substrate preference and show that OtsA is regulated...

    Vítor Mendes, Marta Acebrón-García-de-Eulate, Nupur Verma, Michal Blaszczyk, Márcio V. B. Dias, Tom L. Blundell
    26 Nov 2019
  • Transmembrane Prolines Mediate Signal Sensing and Decoding in <span class="named-content genus-species" id="named-content-1">Bacillus subtilis</span> DesK Histidine Kinase
    Research Article | Molecular Biology and Physiology
    Transmembrane Prolines Mediate Signal Sensing and Decoding in Bacillus subtilis DesK Histidine Kinase

    Signal sensing and transduction is an essential biological process for cell adaptation and survival. Histidine kinases (HK) are the sensory proteins of two-component systems that control many bacterial responses to different stimuli, like environmental changes. Here, we focused on the HK DesK from Bacillus subtilis, a paradigmatic example of a transmembrane...

    Pilar Fernández, Lucía Porrini, Daniela Albanesi, Luciano A. Abriata, Matteo Dal Peraro, Diego de Mendoza, María C. Mansilla
    26 Nov 2019
  • A Multicomponent Vaccine Provides Immunity against Local and Systemic Infections by Group A Streptococcus across Serotypes
    Research Article | Therapeutics and Prevention
    A Multicomponent Vaccine Provides Immunity against Local and Systemic Infections by Group A Streptococcus across Serotypes

    GAS is among the most common human pathogens and causes a wide variety of diseases, likely more than any other microorganism. The diverse clinical manifestations of GAS may be attributable to its large repertoire of virulence factors that are selectively and synergistically involved in streptococcal pathogenesis. To date, GAS vaccines have not been successful due to multiple serotypes and postinfection sequelae associated with...

    Shuai Bi, Meiyi Xu, Ya Zhou, Xinxin Xing, Adong Shen, Beinan Wang
    26 Nov 2019
  • CD71<sup>+</sup> Erythroid Cells Exacerbate HIV-1 Susceptibility, Mediate <em>trans</em>-Infection, and Harbor Infective Viral Particles
    Research Article | Host-Microbe Biology
    CD71+ Erythroid Cells Exacerbate HIV-1 Susceptibility, Mediate trans-Infection, and Harbor Infective Viral Particles

    Immature red blood cells (erythroid precursors or CD71+ erythroid cells) have a wide range of immunomodulatory properties. In this study, we found that these erythroid precursors are abundant in the human cord blood/placental tissues, in the blood of HIV-infected and anemic individuals. We observed that these cells exacerbate HIV-1 replication/infection in target cells and even make HIV target cells more permissible to HIV...

    Afshin Namdar, Garett Dunsmore, Shima Shahbaz, Petya Koleva, Lai Xu, Juan Jovel, Stan Houston, Shokrollah Elahi
    26 Nov 2019
  • Insect Hsp90 Chaperone Assists <span class="named-content genus-species" id="named-content-1">Bacillus thuringiensis</span> Cry Toxicity by Enhancing Protoxin Binding to the Receptor and by Protecting Protoxin from Gut Protease Degradation
    Research Article | Host-Microbe Biology
    Insect Hsp90 Chaperone Assists Bacillus thuringiensis Cry Toxicity by Enhancing Protoxin Binding to the Receptor and by Protecting Protoxin from Gut Protease Degradation

    Bacillus thuringiensis took advantage of important insect cellular proteins, such as chaperones, involved in maintaining protein homeostasis, to enhance its insecticidal activity. This constitutes a positive loop where the concentrations of Hsp90 and Hsp70 in the gut lumen are likely to increase as midgut cells burst due to Cry1A pore formation action. Hsp90 protects...

    Blanca I. García-Gómez, Sayra N. Cano, Erika E. Zagal, Edgar Dantán-Gonzalez, Alejandra Bravo, Mario Soberón
    26 Nov 2019
  • Redox Regulation of a Light-Harvesting Antenna Complex in an Anoxygenic Phototroph
    Research Article | Molecular Biology and Physiology
    Redox Regulation of a Light-Harvesting Antenna Complex in an Anoxygenic Phototroph

    An essential aspect of the physiology of phototrophic bacteria is their ability to adjust the amount and composition of their light-harvesting apparatus in response to changing environmental conditions. The phototrophic purple bacterium R. palustris adapts its photosystem to a range of light intensities by altering the amount and composition of its peripheral LH...

    Kathryn R. Fixen, Yasuhiro Oda, Caroline S. Harwood
    26 Nov 2019
  • Functionally Overlapping Variants Control Tuberculosis Susceptibility in Collaborative Cross Mice
    Research Article | Host-Microbe Biology
    Functionally Overlapping Variants Control Tuberculosis Susceptibility in Collaborative Cross Mice

    The variable outcome of Mycobacterium tuberculosis infection observed in natural populations is difficult to model in genetically homogeneous small-animal models. The newly developed Collaborative Cross (CC) represents a reproducible panel of genetically diverse mice that display a broad range of phenotypic responses to infection. We explored the genetic basis of this...

    Clare M. Smith, Megan K. Proulx, Rocky Lai, Michael C. Kiritsy, Timothy A. Bell, Pablo Hock, Fernando Pardo-Manuel de Villena, Martin T. Ferris, Richard E. Baker, Samuel M. Behar, Christopher M. Sassetti
    26 Nov 2019
  • Reprogramming of Small Noncoding RNA Populations in Peripheral Blood Reveals Host Biomarkers for Latent and Active <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Infection
    Research Article | Host-Microbe Biology
    Reprogramming of Small Noncoding RNA Populations in Peripheral Blood Reveals Host Biomarkers for Latent and Active Mycobacterium tuberculosis Infection

    Tuberculosis is the infectious disease with the worldwide largest disease burden and there remains a great need for better diagnostic biomarkers to detect latent and active M. tuberculosis infection. RNA molecules hold great promise in this regard, as their levels of expression may differ considerably between infected and uninfected subjects. We have measured...

    Leonardo Silva de Araujo, Marcelo Ribeiro-Alves, Thyago Leal-Calvo, Janaína Leung, Verónica Durán, Mohamed Samir, Steven Talbot, Aravind Tallam, Fernanda Carvalho de Queiroz Mello, Robert Geffers, Maria Helena Féres Saad, Frank Pessler
    3 Dec 2019
  • Embryonic Cells Redistribute SUMO1 upon Forced SUMO1 Overexpression
    Research Article | Molecular Biology and Physiology
    Embryonic Cells Redistribute SUMO1 upon Forced SUMO1 Overexpression

    Embryonic stem (ES) cells exhibit unusual transcriptional, proteomic, and signal response profiles, reflecting their unusual needs for rapid differentiation and replication. The work reported here demonstrated that mouse embryonic cell lines did not tolerate the overexpression of SUMO1, the small ubiquitin-like modifier protein that is covalently attached to many substrates to alter their intracellular localization and functionality....

    Andreia Lee, Yiping Zhu, Yosef Sabo, Stephen P. Goff
    3 Dec 2019
  • Expression of 9-<em>O</em>- and 7,9-<em>O</em>-Acetyl Modified Sialic Acid in Cells and Their Effects on Influenza Viruses
    Research Article | Host-Microbe Biology
    Expression of 9-O- and 7,9-O-Acetyl Modified Sialic Acid in Cells and Their Effects on Influenza Viruses

    Sialic acids are key glycans that are involved in many different normal cellular functions, as well as being receptors for many pathogens. However, Sia come in diverse chemically modified forms. Here, we examined and manipulated the expression of 7,9-O- and 9-O-acetyl modified Sia on cells commonly used in influenza virus and other research by engineering the enzymes that produce or remove the acetyl groups.

    ...
    Karen N. Barnard, Brian R. Wasik, Justin R. LaClair, David W. Buchholz, Wendy S. Weichert, Brynn K. Alford-Lawrence, Hector C. Aguilar, Colin R. Parrish
    3 Dec 2019
  • Fluconazole Monotherapy Is a Suboptimal Option for Initial Treatment of Cryptococcal Meningitis Because of Emergence of Resistance
    Research Article | Therapeutics and Prevention
    Fluconazole Monotherapy Is a Suboptimal Option for Initial Treatment of Cryptococcal Meningitis Because of Emergence of Resistance

    Cryptococcal meningitis is a lethal disease with few treatment options. The incidence remains high and intricately linked with the HIV/AIDS epidemic. In many parts of the world, fluconazole is the only agent that is available for the initial treatment of cryptococcal meningitis despite considerable evidence that it is associated with suboptimal microbiological and clinical outcomes. Fluconazole has a fungistatic mode of action: it...

    William Hope, Neil R. H. Stone, Adam Johnson, Laura McEntee, Nicola Farrington, Anahi Santoro-Castelazo, Xuan Liu, Anita Lucaci, Margaret Hughes, Jason D. Oliver, Charles Giamberardino, Sayoki Mfinanga, Thomas S. Harrison, John R. Perfect, Tihana Bicanic
    3 Dec 2019
  • A Conserved Regulatory Circuit Controls Large Adhesins in <span class="named-content genus-species" id="named-content-1">Vibrio cholerae</span>
    Research Article | Molecular Biology and Physiology
    A Conserved Regulatory Circuit Controls Large Adhesins in Vibrio cholerae

    Vibrio cholerae, the causative agent of the diarrheal disease cholera, benefits from a sessile biofilm lifestyle that enhances survival outside the host but also contributes to host colonization and infectivity. The bacterial second messenger c-di-GMP has been identified as a central regulator of biofilm formation, including in...

    Giordan Kitts, Krista M. Giglio, David Zamorano-Sánchez, Jin Hwan Park, Loni Townsley, Richard B. Cooley, Benjamin R. Wucher, Karl E. Klose, Carey D. Nadell, Fitnat H. Yildiz, Holger Sondermann
    3 Dec 2019
  • Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance
    Editor's Pick Research Article | Host-Microbe Biology
    Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance

    Immunocompromised individuals often become symptomatic with infections which are normally fairly asymptomatic in healthy individuals. The particular mechanisms that underlie susceptibility to coinfections in human immunodeficiency virus (HIV)-infected individuals are multifaceted. ZIKV and other flaviviruses are sensitive to neutralizing antibodies, whose production can be limited in HIV-infected individuals but are also sensitive to...

    Carol L. Vinton, Samuel J. Magaziner, Kimberly A. Dowd, Shelly J. Robertson, Emerito Amaro-Carambot, Erik P. Karmele, Alexandra M. Ortiz, Carly E. Starke, Joseph C. Mudd, Stephen S. Whitehead, Sonja M. Best, Theodore C. Pierson, Heather D. Hickman, Jason M. Brenchley
    3 Dec 2019
  • Developmentally Regulated Oscillations in the Expression of UV Repair Genes in a Soilborne Plant Pathogen Dictate UV Repair Efficiency and Survival
    Research Article | Molecular Biology and Physiology
    Developmentally Regulated Oscillations in the Expression of UV Repair Genes in a Soilborne Plant Pathogen Dictate UV Repair Efficiency and Survival

    Fusarium oxysporum infects plants through the roots and therefore is not exposed to the sun regularly. However, the ability to survive sun exposure expands the distribution of the population. UV from the sun is toxic and mutagenic, and to survive sun exposure, fungi encode several DNA repair mechanisms. We found that...

    Shira Milo-Cochavi, Sheera Adar, Shay Covo
    3 Dec 2019
  • A Porcine <em>Ex Vivo</em> Lung Perfusion Model To Investigate Bacterial Pathogenesis
    Research Article | Host-Microbe Biology
    A Porcine Ex Vivo Lung Perfusion Model To Investigate Bacterial Pathogenesis

    The implementation of infection models that approximate human disease is essential to understand infections and for testing new therapies before they enter into clinical stages. Rodents are used in most preclinical studies, although the differences between mice and humans have fueled the conclusion that murine studies are unreliable predictors of human outcomes. In this study, we have developed a whole-lung porcine model of infection...

    Amy Dumigan, Marianne Fitzgerald, Joana Sá-Pessoa Graca Santos, Umar Hamid, Cecilia M. O’Kane, Danny F. McAuley, Jose A. Bengoechea
    3 Dec 2019
  • Interferon-Responsive Genes Are Targeted during the Establishment of Human Cytomegalovirus Latency
    Research Article | Host-Microbe Biology
    Interferon-Responsive Genes Are Targeted during the Establishment of Human Cytomegalovirus Latency

    Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus which infects 50 to 100% of humans worldwide. HCMV causes a lifelong subclinical infection in immunocompetent individuals but is a serious cause of mortality and morbidity in the immunocompromised and neonates. In particular, reactivation of HCMV in the transplant setting is a major cause of transplant failure and related disease. Therefore, a molecular understanding of HCMV...

    Elizabeth G. Elder, Benjamin A. Krishna, James Williamson, Eleanor Y. Lim, Emma Poole, George X. Sedikides, Mark Wills, Christine M. O’Connor, Paul J. Lehner, John Sinclair
    3 Dec 2019
  • Integrative Activity of Mating Loci, Environmentally Responsive Genes, and Secondary Metabolism Pathways during Sexual Development of <span class="named-content genus-species" id="named-content-1">Chaetomium globosum</span>
    Research Article | Ecological and Evolutionary Science
    Integrative Activity of Mating Loci, Environmentally Responsive Genes, and Secondary Metabolism Pathways during Sexual Development of Chaetomium globosum

    Fungal diversity has amazed evolutionary biologists for decades. One societally important aspect of this diversity manifests in traits that enable pathogenicity. The opportunistic pathogen Chaetomium globosum is well adapted to a high-humidity environment and produces numerous secondary metabolites that defend it from predation. Many of these chemicals can threaten...

    Zheng Wang, Francesc López-Giráldez, Junrui Wang, Frances Trail, Jeffrey P. Townsend
    10 Dec 2019
  • Inhibition of Neutrophil Primary Granule Release during <span class="named-content genus-species" id="named-content-1">Yersinia pestis</span> Pulmonary Infection
    Research Article | Host-Microbe Biology
    Inhibition of Neutrophil Primary Granule Release during Yersinia pestis Pulmonary Infection

    Yersinia pestis is the causative agent of plague and is one of the deadliest human pathogens. The pneumonic form of Y. pestis infection has played a critical role in the severity of both historical and modern plague outbreaks, yet the host-pathogen interactions that govern the lethality of...

    Kara R. Eichelberger, Grant S. Jones, William E. Goldman
    10 Dec 2019
  • A Mechanosensitive Channel Governs Lipid Flippase-Mediated Echinocandin Resistance in <span class="named-content genus-species" id="named-content-1">Cryptococcus neoformans</span>
    Editor's Pick Research Article | Therapeutics and Prevention
    A Mechanosensitive Channel Governs Lipid Flippase-Mediated Echinocandin Resistance in Cryptococcus neoformans

    Cryptococcus neoformans is the leading cause of fungal meningitis, accounting for ∼15% of HIV/AIDS-related deaths, but treatment options for cryptococcosis are limited. Echinocandins are the newest fungicidal drug class introduced but are ineffective in treating cryptococcosis. Our previous study identified the lipid flippase subunit Cdc50 as a contributor to...

    Chengjun Cao, Yina Wang, Seema Husain, Patricia Soteropoulos, Chaoyang Xue
    10 Dec 2019
  • Bottom-Up Fabrication of Protein Nanowires via Controlled Self-Assembly of Recombinant <em>Geobacter</em> Pilins
    Editor's Pick Research Article | Applied and Environmental Science
    Bottom-Up Fabrication of Protein Nanowires via Controlled Self-Assembly of Recombinant Geobacter Pilins

    The discovery in 2005 of conductive protein appendages (pili) in the metal-reducing bacterium Geobacter sulfurreducens challenged our understanding of biological electron transfer and pioneered studies in electromicrobiology that revealed the electronic basis of many microbial metabolisms and interactions. The protein nature of the pili afforded opportunities for...

    K. M. Cosert, Angelines Castro-Forero, Rebecca J. Steidl, Robert M. Worden, G. Reguera
    10 Dec 2019
  • The Metabolite Repair Enzyme Phosphoglycolate Phosphatase Regulates Central Carbon Metabolism and Fosmidomycin Sensitivity in <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span>
    Research Article | Host-Microbe Biology
    The Metabolite Repair Enzyme Phosphoglycolate Phosphatase Regulates Central Carbon Metabolism and Fosmidomycin Sensitivity in Plasmodium falciparum

    The malaria parasite has a voracious appetite, requiring large amounts of glucose and nutrients for its rapid growth and proliferation inside human red blood cells. The host cell is resource rich, but this is a double-edged sword; nutrient excess can lead to undesirable metabolic reactions and harmful by-products. Here, we demonstrate that the parasite possesses a metabolite repair enzyme (PGP) that suppresses harmful metabolic by-...

    Laure Dumont, Mark B. Richardson, Phillip van der Peet, Danushka S. Marapana, Tony Triglia, Matthew W. A. Dixon, Alan F. Cowman, Spencer J. Williams, Leann Tilley, Malcolm J. McConville, Simon A. Cobbold
    10 Dec 2019
  • The Human Cytomegalovirus Nonstructural Glycoprotein UL148 Reorganizes the Endoplasmic Reticulum
    Research Article | Host-Microbe Biology
    The Human Cytomegalovirus Nonstructural Glycoprotein UL148 Reorganizes the Endoplasmic Reticulum

    Perturbations to endoplasmic reticulum (ER) morphology occur during infection with various intracellular pathogens and in certain genetic disorders. We identify that a human cytomegalovirus (HCMV) gene product, UL148, profoundly reorganizes the ER during infection and is sufficient to do so when expressed on its own. Our results reveal that UL148-dependent reorganization of the ER is a prominent feature of HCMV-infected cells. Moreover...

    Hongbo Zhang, Clarissa Read, Christopher C. Nguyen, Mohammed N. A. Siddiquey, Chaowei Shang, Cameron M. Hall, Jens von Einem, Jeremy P. Kamil
    10 Dec 2019
  • The Emergence of Successful <span class="named-content genus-species" id="named-content-1">Streptococcus pyogenes</span> Lineages through Convergent Pathways of Capsule Loss and Recombination Directing High Toxin Expression
    Research Article | Ecological and Evolutionary Science
    The Emergence of Successful Streptococcus pyogenes Lineages through Convergent Pathways of Capsule Loss and Recombination Directing High Toxin Expression

    Streptococcus pyogenes is a genetically diverse pathogen, with over 200 different genotypes defined by emm typing, but only a minority of these genotypes are responsible for the majority of human infection in high-income countries. Two prevalent genotypes associated with disease rose to international dominance following recombination of a toxin locus that...

    Claire E. Turner, Matthew T. G. Holden, Beth Blane, Carolyne Horner, Sharon J. Peacock, Shiranee Sriskandan
    10 Dec 2019

Erratum

  • Erratum for Lowey et al., “Hepatitis C Virus Infection Induces Hepatic Expression of NF-κB-Inducing Kinase and Lipogenesis by Downregulating miR-122”
    Erratum
    Erratum for Lowey et al., “Hepatitis C Virus Infection Induces Hepatic Expression of NF-κB-Inducing Kinase and Lipogenesis by Downregulating miR-122”
    Brianna Lowey, Laura Hertz, Stephan Chiu, Kristin Valdez, Qisheng Li, T. Jake Liang
    3 Dec 2019
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