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  • Conserved Outer Tegument Component UL11 from Herpes Simplex Virus 1 Is an Intrinsically Disordered, RNA-Binding Protein.
    mBio (IF 6.784) Pub Date : 2020-05-05
    Claire M Metrick,Andrea L Koenigsberg,Ekaterina E Heldwein

    A distinguishing morphological feature of all herpesviruses is the multiprotein tegument layer located between the nucleocapsid and lipid envelope of the virion. Tegument proteins play multiple roles in viral replication, including viral assembly, but we do not yet understand their individual functions or how the tegument is assembled and organized. UL11, the smallest tegument protein, is important

    更新日期:2020-06-30
  • Access to PCNA by Srs2 and Elg1 Controls the Choice between Alternative Repair Pathways in Saccharomyces cerevisiae.
    mBio (IF 6.784) Pub Date : 2020-05-05
    Matan Arbel,Alex Bronstein,Soumitra Sau,Batia Liefshitz,Martin Kupiec

    During DNA replication, stalling can occur when the replicative DNA polymerases encounter lesions or hard-to replicate regions. Under these circumstances, the processivity factor PCNA gets ubiquitylated at lysine 164, inducing the DNA damage tolerance (DDT) mechanisms that can bypass lesions encountered during DNA replication. PCNA can also be SUMOylated at the same residue or at lysine 127. Surprisingly

    更新日期:2020-06-30
  • Glycerol Monolaurate, an Analogue to a Factor Secreted by Lactobacillus, Is Virucidal against Enveloped Viruses, Including HIV-1.
    mBio (IF 6.784) Pub Date : 2020-05-05
    Jennifer L Welch,Jinhua Xiang,Chioma M Okeoma,Patrick M Schlievert,Jack T Stapleton

    The vaginal microbiota influences sexual transmission of human immunodeficiency virus type 1 (HIV-1). Colonization of the vaginal tract is normally dominated by Lactobacillus species. Both Lactobacillus and Enterococcus faecalis may secrete reutericyclin, which inhibits the growth of a variety of pathogenic bacteria. Increasing evidence suggests a potential therapeutic role for an analogue of reutericyclin

    更新日期:2020-06-30
  • Loss of Bacterial Cell Pole Stabilization in Caulobacter crescentus Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed Antibiotics.
    mBio (IF 6.784) Pub Date : 2020-05-05
    Simon-Ulysse Vallet,Lykke Haastrup Hansen,Freja Cecillie Bistrup,Signe Aagaard Laursen,Julien Bortoli Chapalay,Marc Chambon,Gerardo Turcatti,Patrick H Viollier,Clare L Kirkpatrick

    Rod-shaped bacteria frequently localize proteins to one or both cell poles in order to regulate processes such as chromosome replication or polar organelle development. However, the roles of polar factors in responses to extracellular stimuli have been generally unexplored. We employed chemical-genetic screening to probe the interaction between one such factor from Caulobacter crescentus, TipN, and

    更新日期:2020-06-30
  • Linearized Siderophore Products Secreted via MacAB Efflux Pump Protect Salmonella enterica Serovar Typhimurium from Oxidative Stress.
    mBio (IF 6.784) Pub Date : 2020-05-05
    L M Bogomolnaya,R Tilvawala,J R Elfenbein,J D Cirillo,H L Andrews-Polymenis

    Nontyphoidal salmonellae (NTS) are exposed to reactive oxygen species (ROS) during their residency in the gut. To survive oxidative stress encountered during infection, salmonellae employ several mechanisms. One of these mechanisms involves the multidrug efflux pump MacAB, although the natural substrate of this pump has not been identified. MacAB homologs in pseudomonads secrete products of nonribosomal

    更新日期:2020-06-30
  • Threats Posed by the Fungal Kingdom to Humans, Wildlife, and Agriculture.
    mBio (IF 6.784) Pub Date : 2020-05-05
    Matthew C Fisher,Sarah J Gurr,Christina A Cuomo,David S Blehert,Hailing Jin,Eva H Stukenbrock,Jason E Stajich,Regine Kahmann,Charles Boone,David W Denning,Neil A R Gow,Bruce S Klein,James W Kronstad,Donald C Sheppard,John W Taylor,Gerard D Wright,Joseph Heitman,Arturo Casadevall,Leah E Cowen

    The fungal kingdom includes at least 6 million eukaryotic species and is remarkable with respect to its profound impact on global health, biodiversity, ecology, agriculture, manufacturing, and biomedical research. Approximately 625 fungal species have been reported to infect vertebrates, 200 of which can be human associated, either as commensals and members of our microbiome or as pathogens that cause

    更新日期:2020-06-30
  • Systemic Inflammatory Mediators Are Effective Biomarkers for Predicting Adverse Outcomes in Clostridioides difficile Infection.
    mBio (IF 6.784) Pub Date : 2020-05-05
    Michael G Dieterle,Rosemary Putler,D Alexander Perry,Anitha Menon,Lisa Abernathy-Close,Naomi S Perlman,Aline Penkevich,Alex Standke,Micah Keidan,Kimberly C Vendrov,Ingrid L Bergin,Vincent B Young,Krishna Rao

    Clostridioides difficile infection (CDI) can result in severe disease and death, with no accurate models that allow for early prediction of adverse outcomes. To address this need, we sought to develop serum-based biomarker models to predict CDI outcomes. We prospectively collected sera ≤48 h after diagnosis of CDI in two cohorts. Biomarkers were measured with a custom multiplex bead array assay. Patients

    更新日期:2020-06-30
  • Cell Wall Composition Heterogeneity between Single Cells in Aspergillus fumigatus Leads to Heterogeneous Behavior during Antifungal Treatment and Phagocytosis.
    mBio (IF 6.784) Pub Date : 2020-05-12
    Robert-Jan Bleichrodt,Peter Foster,Gareth Howell,Jean-Paul Latgé,Nick D Read

    Aspergillus fumigatus can cause a variety of lung diseases in immunocompromised patients, including life-threatening invasive aspergillosis. There are only three main classes of antifungal drugs currently used to treat aspergillosis, and antifungal resistance is increasing. Experimental results in fungal biology research are usually obtained as average measurements across whole populations while ignoring

    更新日期:2020-06-30
  • Spleen Tyrosine Kinase Is a Critical Regulator of Neutrophil Responses to Candida Species.
    mBio (IF 6.784) Pub Date : 2020-05-12
    Paige E Negoro,Shuying Xu,Zeina Dagher,Alex Hopke,Jennifer L Reedy,Michael B Feldman,Nida S Khan,Adam L Viens,Natalie J Alexander,Natalie J Atallah,Allison K Scherer,Richard A Dutko,Jane Jeffery,John F Kernien,J Scott Fites,Jeniel E Nett,Bruce S Klein,Jatin M Vyas,Daniel Irimia,David B Sykes,Michael K Mansour

    Invasive fungal infections constitute a lethal threat, with patient mortality as high as 90%. The incidence of invasive fungal infections is increasing, especially in the setting of patients receiving immunomodulatory agents, chemotherapy, or immunosuppressive medications following solid-organ or bone marrow transplantation. In addition, inhibitors of spleen tyrosine kinase (Syk) have been recently

    更新日期:2020-06-30
  • An Infection-Based Murine Model for Papillomavirus-Associated Head and Neck Cancer.
    mBio (IF 6.784) Pub Date : 2020-05-12
    Tao Wei,Darya Buehler,Ella Ward-Shaw,Paul F Lambert

    Human papillomavirus (HPV) is the most common sexually transmitted pathogen, and high-risk HPVs contribute to 5% of human cancers, including 25% of head and neck squamous cell carcinomas (HNSCCs). Despite the significant role played by HPVs in HNSCC, there is currently no available in vivo system to model the process from papillomavirus infection to virus-induced HNSCC. In this paper, we describe an

    更新日期:2020-06-30
  • Herpesvirus Entry Mediator Binding Partners Mediate Immunopathogenesis of Ocular Herpes Simplex Virus 1 Infection.
    mBio (IF 6.784) Pub Date : 2020-05-12
    Seo J Park,Rachel E Riccio,Sarah J Kopp,Igal Ifergan,Stephen D Miller,Richard Longnecker

    Ocular herpes simplex virus 1 (HSV-1) infection leads to an immunopathogenic disease called herpes stromal keratitis (HSK), in which CD4+ T cell-driven inflammation contributes to irreversible damage to the cornea. Herpesvirus entry mediator (HVEM) is an immune modulator that activates stimulatory and inhibitory cosignals by interacting with its binding partners, LIGHT (TNFSF14), BTLA (B and T lymphocyte

    更新日期:2020-06-30
  • Core N-Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death.
    mBio (IF 6.784) Pub Date : 2020-05-12
    Eun Jung Thak,Su-Bin Lee,Shengjie Xu-Vanpala,Dong-Jik Lee,Seung-Yeon Chung,Yong-Sun Bahn,Doo-Byoung Oh,Mari L Shinohara,Hyun Ah Kang

    Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals. To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER). Deletion of ALG3

    更新日期:2020-06-30
  • CD8+ T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A.
    mBio (IF 6.784) Pub Date : 2020-05-12
    Facundo Fiocca Vernengo,Cristian G Beccaria,Cintia L Araujo Furlan,Jimena Tosello Boari,Laura Almada,Melisa Gorosito Serrán,Yamila Gazzoni,Carolina L Montes,Eva V Acosta Rodríguez,Adriana Gruppi

    Treatment with anti-CD20, used in many diseases in which B cells play a pathogenic role, has been associated with susceptibility to intracellular infections. Here, we studied the effect of anti-CD20 injection on CD8+ T cell immunity using an experimental model of Trypanosoma cruzi infection, in which CD8+ T cells play a pivotal role. C57BL/6 mice were treated with anti-CD20 for B cell depletion prior

    更新日期:2020-06-30
  • Mutations in TAC1B: a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris.
    mBio (IF 6.784) Pub Date : 2020-05-12
    Jeffrey M Rybak,José F Muñoz,Katherine S Barker,Josie E Parker,Brooke D Esquivel,Elizabeth L Berkow,Shawn R Lockhart,Lalitha Gade,Glen E Palmer,Theodore C White,Steve L Kelly,Christina A Cuomo,P David Rogers

    Candida auris has emerged as a multidrug-resistant pathogen of great clinical concern. Approximately 90% of clinical C. auris isolates are resistant to fluconazole, the most commonly prescribed antifungal agent, and yet it remains unknown what mechanisms underpin this fluconazole resistance. To identify novel mechanisms contributing to fluconazole resistance in C. auris, fluconazole-susceptible C.

    更新日期:2020-06-30
  • Carboxylic Acid Transporters in Candida Pathogenesis.
    mBio (IF 6.784) Pub Date : 2020-05-12
    Rosana Alves,Maria Sousa-Silva,Daniel Vieira,Pedro Soares,Yasmin Chebaro,Michael C Lorenz,Margarida Casal,Isabel Soares-Silva,Sandra Paiva

    Opportunistic pathogens such as Candida species can use carboxylic acids, like acetate and lactate, to survive and successfully thrive in different environmental niches. These nonfermentable substrates are frequently the major carbon sources present in certain human body sites, and their efficient uptake by regulated plasma membrane transporters plays a critical role in such nutrient-limited conditions

    更新日期:2020-06-30
  • The NtrYX Two-Component System Regulates the Bacterial Cell Envelope.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Kimberly C Lemmer,François Alberge,Kevin S Myers,Alice C Dohnalkova,Ryan E Schaub,Jonathan D Lenz,Saheed Imam,Joseph P Dillard,Daniel R Noguera,Timothy J Donohue

    Activity of the NtrYX two-component system has been associated with important processes in diverse bacteria, ranging from symbiosis to nitrogen and energy metabolism. In the facultative alphaproteobacterium Rhodobacter sphaeroides, loss of the two-component system NtrYX results in increased lipid production and sensitivity to some known cell envelope-active compounds. In this study, we show that NtrYX

    更新日期:2020-06-30
  • Comparing Early Eukaryotic Integration of Mitochondria and Chloroplasts in the Light of Internal ROS Challenges: Timing is of the Essence.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Dave Speijer,Michael Hammond,Julius Lukeš

    When trying to reconstruct the evolutionary trajectories during early eukaryogenesis, one is struck by clear differences in the developments of two organelles of endosymbiotic origin: the mitochondrion and the chloroplast. From a symbiogenic perspective, eukaryotic development can be interpreted as a process in which many of the defining eukaryotic characteristics arose as a result of mutual adaptions

    更新日期:2020-06-30
  • A Chemical Counterpunch: Chromobacterium violaceum ATCC 31532 Produces Violacein in Response to Translation-Inhibiting Antibiotics.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Gabriel L Lozano,Changhui Guan,Yanzhuan Cao,Bradley R Borlee,Nichole A Broderick,Eric V Stabb,Jo Handelsman

    Antibiotics produced by bacteria play important roles in microbial interactions and competition Antibiosis can induce resistance mechanisms in target organisms, and at sublethal doses, antibiotics have been shown to globally alter gene expression patterns. Here, we show that hygromycin A from Streptomyces sp. strain 2AW. induces Chromobacterium violaceum ATCC 31532 to produce the purple antibiotic

    更新日期:2020-06-30
  • An Essential Membrane Protein Modulates the Proteolysis of LpxC to Control Lipopolysaccharide Synthesis in Escherichia coli.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Elayne M Fivenson,Thomas G Bernhardt

    Gram-negative bacteria are surrounded by a complex cell envelope that includes two membranes. The outer membrane prevents many drugs from entering these cells and is thus a major determinant of their intrinsic antibiotic resistance. This barrier function is imparted by the asymmetric architecture of the membrane with lipopolysaccharide (LPS) in the outer leaflet and phospholipids in the inner leaflet

    更新日期:2020-06-30
  • A New Pneumococcal Capsule Type, 10D, is the 100th Serotype and Has a Large cps Fragment from an Oral Streptococcus.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Feroze Ganaie,Jamil S Saad,Lesley McGee,Andries J van Tonder,Stephen D Bentley,Stephanie W Lo,Rebecca A Gladstone,Paul Turner,Jeremy D Keenan,Robert F Breiman,Moon H Nahm

    Streptococcus pneumoniae (pneumococcus) is a major human pathogen producing structurally diverse capsular polysaccharides. Widespread use of highly successful pneumococcal conjugate vaccines (PCVs) targeting pneumococcal capsules has greatly reduced infections by the vaccine types but increased infections by nonvaccine serotypes. Herein, we report a new and the 100th capsule type, named serotype 10D

    更新日期:2020-06-30
  • Host Fatty Acid Utilization by Staphylococcus aureus at the Infection Site.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Matthew W Frank,Jiangwei Yao,Justin L Batte,Jessica M Gullett,Chitra Subramanian,Jason W Rosch,Charles O Rock

    Staphylococcus aureus utilizes the fatty acid (FA) kinase system to activate exogenous FAs for membrane synthesis. We developed a lipidomics workflow to determine the membrane phosphatidylglycerol (PG) molecular species synthesized by S. aureus at the thigh infection site. Wild-type S. aureus utilizes both host palmitate and oleate to acylate the 1 position of PG, and the 2 position is occupied by

    更新日期:2020-06-30
  • Lipoprotein Processing and Sorting in Helicobacter pylori.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Mark S McClain,Bradley J Voss,Timothy L Cover

    Our current understanding of lipoprotein synthesis and localization in Gram-negative bacteria is based primarily on studies of Escherichia coli. Newly synthesized E. coli prolipoproteins undergo posttranslational modifications catalyzed by three essential enzymes (Lgt, LspA, and Lnt). The mature lipoproteins are then sorted to the inner or outer membrane via the Lol system (LolABCDE). Recent studies

    更新日期:2020-06-30
  • Persistent Legionnaires' Disease and Associated Antibiotic Treatment Engender a Highly Disturbed Pulmonary Microbiome Enriched in Opportunistic Microorganisms.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Ana Elena Pérez-Cobas,Christophe Ginevra,Christophe Rusniok,Sophie Jarraud,Carmen Buchrieser

    Despite the importance of pneumonia to public health, little is known about the composition of the lung microbiome during infectious diseases, such as pneumonia, and how it evolves during antibiotic therapy. To study the possible relation of the pulmonary microbiome to the severity and outcome of this respiratory disease, we analyzed the dynamics of the pathogen and the human lung microbiome during

    更新日期:2020-06-30
  • Coevolution of Eukaryote-like Vps4 and ESCRT-III Subunits in the Asgard Archaea.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Zhongyi Lu,Ting Fu,Tianyi Li,Yang Liu,Siyu Zhang,Jinquan Li,Junbiao Dai,Eugene V Koonin,Guohui Li,Huiying Chu,Meng Li

    The emergence of the endomembrane system is a key step in the evolution of cellular complexity during eukaryogenesis. The endosomal sorting complex required for transport (ESCRT) machinery is essential and required for the endomembrane system functions in eukaryotic cells. Recently, genes encoding eukaryote-like ESCRT protein components have been identified in the genomes of Asgard archaea, a newly

    更新日期:2020-06-30
  • Emergence of Enteroaggregative Escherichia coli within the ST131 Lineage as a Cause of Extraintestinal Infections.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Erik J Boll,Søren Overballe-Petersen,Henrik Hasman,Louise Roer,Kim Ng,Flemming Scheutz,Anette M Hammerum,Arnold Dungu,Frank Hansen,Thor B Johannesen,Abigail Johnson,Divek T Nair,Berit Lilje,Dennis S Hansen,Karen A Krogfelt,Timothy J Johnson,Lance B Price,James R Johnson,Carsten Struve,Bente Olesen,Marc Stegger

    Escherichia coli sequence type 131 (ST131) is a major cause of urinary and bloodstream infections. Its association with extended-spectrum β-lactamases (ESBLs) significantly complicates treatment. Its best-described component is the rapidly expanding H30Rx clade, containing allele 30 of the type 1 fimbrial adhesin gene fimH. This lineage appears to have emerged in the United States and spread around

    更新日期:2020-06-30
  • A Rapidly Evolving Polybasic Motif Modulates Bacterial Detection by Guanylate Binding Proteins.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Kristin M Kohler,Miriam Kutsch,Anthony S Piro,Graham D Wallace,Jörn Coers,Matthew F Barber

    Cell-autonomous immunity relies on the rapid detection of invasive pathogens by host proteins. Guanylate binding proteins (GBPs) have emerged as key mediators of vertebrate immune defense through their ability to recognize a diverse array of intracellular pathogens and pathogen-containing cellular compartments. Human and mouse GBPs have been shown to target distinct groups of microbes, although the

    更新日期:2020-06-30
  • Lipid-Specific Labeling of Enveloped Viruses with Quantum Dots for Single-Virus Tracking.
    mBio (IF 6.784) Pub Date : 2020-05-19
    Li-Juan Zhang,Shaobo Wang,Li Xia,Cheng Lv,Hong-Wu Tang,Zhenpu Liang,Gengfu Xiao,Dai-Wen Pang

    Quantum dots (QDs) possess optical properties of superbright fluorescence, excellent photostability, narrow emission spectra, and optional colors. Labeled with QDs, single molecules/viruses can be rapidly and continuously imaged for a long time, providing more detailed information than when labeled with other fluorophores. While they are widely used to label proteins in single-molecule-tracking studies

    更新日期:2020-06-30
  • Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets.
    mBio (IF 6.784) Pub Date : 2020-05-22
    Su-Jin Park,Kwang-Min Yu,Young-Il Kim,Se-Mi Kim,Eun-Ha Kim,Seong-Gyu Kim,Eun Ji Kim,Mark Anthony B Casel,Rare Rollon,Seung-Gyu Jang,Min-Hyeok Lee,Jae-Hyung Chang,Min-Suk Song,Hye Won Jeong,Younho Choi,Weiqiang Chen,Woo-Jin Shin,Jae U Jung,Young Ki Choi

    Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2)

    更新日期:2020-06-30
  • Linking the Dynamic Response of the Carbon Dioxide-Concentrating Mechanism to Carbon Assimilation Behavior in Fremyella diplosiphon.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Brandon A Rohnke,Kiara J Rodríguez Pérez,Beronda L Montgomery

    Cyanobacteria use a carbon dioxide (CO2)-concentrating mechanism (CCM) that enhances their carbon fixation efficiency and is regulated by many environmental factors that impact photosynthesis, including carbon availability, light levels, and nutrient access. Efforts to connect the regulation of the CCM by these factors to functional effects on carbon assimilation rates have been complicated by the

    更新日期:2020-06-30
  • Cryo-EM Structures of a Gonococcal Multidrug Efflux Pump Illuminate a Mechanism of Drug Recognition and Resistance.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Meinan Lyu,Mitchell A Moseng,Jennifer L Reimche,Concerta L Holley,Vijaya Dhulipala,Chih-Chia Su,William M Shafer,Edward W Yu

    Neisseria gonorrhoeae is an obligate human pathogen and causative agent of the sexually transmitted infection (STI) gonorrhea. The most predominant and clinically important multidrug efflux system in N. gonorrhoeae is the multiple transferrable resistance (Mtr) pump, which mediates resistance to a number of different classes of structurally diverse antimicrobial agents, including clinically used antibiotics

    更新日期:2020-06-30
  • Decreased, Deformed, Defective-How HIV-1 Vpu Targets Peroxisomes.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Kristina Hopfensperger,Daniel Sauter

    Peroxisomes are found in essentially all eukaryotic cells and have been described as important hubs in innate sensing and the induction of type III interferons upon viral infection. Nevertheless, it remains poorly investigated how viral pathogens modulate biogenesis or function of peroxisomes to evade innate sensing and restriction. In a recent study, Hobman and colleagues found that the accessory

    更新日期:2020-06-30
  • Molecular Insight into TdfH-Mediated Zinc Piracy from Human Calprotectin by Neisseria gonorrhoeae.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Michael T Kammerman,Aloke Bera,Runrun Wu,Simone A Harrison,C Noel Maxwell,Karl Lundquist,Nicholas Noinaj,Walter J Chazin,Cynthia Nau Cornelissen

    Neisseria gonorrhoeae, responsible for the sexually transmitted infection gonorrhea, is an obligate human pathogen exquisitely adapted for survival on mucosal surfaces of humans. This host-pathogen relationship has resulted in evolution by N. gonorrhoeae of pathways that enable the use of host metalloproteins as required nutrients through the deployment of outer membrane-bound TonB-dependent transporters

    更新日期:2020-06-30
  • Parallel Evolution of Tobramycin Resistance across Species and Environments.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Michelle R Scribner,Alfonso Santos-Lopez,Christopher W Marshall,Christopher Deitrick,Vaughn S Cooper

    Different species exposed to a common stress may adapt by mutations in shared pathways or in unique systems, depending on how past environments have molded their genomes. Understanding how diverse bacterial pathogens evolve in response to an antimicrobial treatment is a pressing example of this problem, where discovery of molecular parallelism could lead to clinically useful predictions. Evolution

    更新日期:2020-06-30
  • The Innate Immune Response to Herpes Simplex Virus 1 Infection Is Dampened in the Newborn Brain and Can Be Modulated by Exogenous Interferon Beta To Improve Survival.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Daniel Giraldo,Douglas R Wilcox,Richard Longnecker

    Newborns are particularly susceptible to severe forms of herpes simplex virus 1 (HSV-1) infection, including encephalitis and multisystemic disseminated disease. The underlying age-dependent differences in the immune response that explain this increased susceptibility relative to the adult population remain largely understudied. Using a murine model of HSV-1 infection, we found that newborn mice are

    更新日期:2020-06-30
  • Immune Profiling To Predict Outcome of Clostridioides difficile Infection.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Mayuresh M Abhyankar,Jennie Z Ma,Kenneth W Scully,Andrew J Nafziger,Alyse L Frisbee,Mahmoud M Saleh,Gregory R Madden,Ann R Hays,Mendy Poulter,William A Petri

    There is a pressing need for biomarker-based models to predict mortality from and recurrence of Clostridioides difficile infection (CDI). Risk stratification would enable targeted interventions such as fecal microbiota transplant, antitoxin antibodies, and colectomy for those at highest risk. Because severity of CDI is associated with the immune response, we immune profiled patients at the time of

    更新日期:2020-06-30
  • Conidial Melanin of the Human-Pathogenic Fungus Aspergillus fumigatus Disrupts Cell Autonomous Defenses in Amoebae.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Iuliia Ferling,Joe Dan Dunn,Alexander Ferling,Thierry Soldati,Falk Hillmann

    The human-pathogenic fungus Aspergillus fumigatus is a ubiquitous saprophyte that causes fatal lung infections in immunocompromised individuals. Following inhalation, conidia are ingested by innate immune cells and can arrest phagolysosome maturation. How this virulence trait could have been selected for in natural environments is unknown. Here, we found that surface exposure of the green pigment 1

    更新日期:2020-06-30
  • Interactions of Symbiotic Partners Drive the Development of a Complex Biogeography in the Squid-Vibrio Symbiosis.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Tara Essock-Burns,Clotilde Bongrand,William E Goldman,Edward G Ruby,Margaret J McFall-Ngai

    Microbes live in complex microniches within host tissues, but how symbiotic partners communicate to create such niches during development remains largely unexplored. Using confocal microscopy and symbiont genetics, we characterized the shaping of host microenvironments during light organ colonization of the squid Euprymna scolopes by the bacterium Vibrio fischeri. During embryogenesis, three pairs

    更新日期:2020-06-30
  • Hadaka Virus 1: a Capsidless Eleven-Segmented Positive-Sense Single-Stranded RNA Virus from a Phytopathogenic Fungus, Fusarium oxysporum.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Yukiyo Sato,Wajeeha Shamsi,Atif Jamal,Muhammad Faraz Bhatti,Hideki Kondo,Nobuhiro Suzuki

    The search for viruses infecting fungi, or mycoviruses, has extended our knowledge about the diversity of RNA viruses, as exemplified by the discovery of polymycoviruses, a phylogenetic group of multisegmented RNA viruses with unusual forms. The genomic RNAs of known polymycoviruses, which show a phylogenetic affinity for animal positive-sense single-stranded RNA [(+)RNA] viruses such as caliciviruses

    更新日期:2020-06-30
  • The HIV-1 Env gp120 Inner Domain Shapes the Phe43 Cavity and the CD4 Binding Site.
    mBio (IF 6.784) Pub Date : 2020-05-26
    Jérémie Prévost,William D Tolbert,Halima Medjahed,Rebekah T Sherburn,Navid Madani,Daria Zoubchenok,Gabrielle Gendron-Lepage,Althea E Gaffney,Melissa C Grenier,Sharon Kirk,Natasha Vergara,Changze Han,Brendan T Mann,Agnès L Chénine,Adel Ahmed,Irwin Chaiken,Frank Kirchhoff,Beatrice H Hahn,Hillel Haim,Cameron F Abrams,Amos B Smith,Joseph Sodroski,Marzena Pazgier,Andrés Finzi

    The HIV-1 envelope glycoproteins (Env) undergo conformational changes upon interaction of the gp120 exterior glycoprotein with the CD4 receptor. The gp120 inner domain topological layers facilitate the transition of Env to the CD4-bound conformation. CD4 engages gp120 by introducing its phenylalanine 43 (Phe43) in a cavity (“the Phe43 cavity”) located at the interface between the inner and outer gp120

    更新日期:2020-06-30
  • Pandemic COVID-19 Joins History's Pandemic Legion.
    mBio (IF 6.784) Pub Date : 2020-05-29
    David M Morens,Peter Daszak,Howard Markel,Jeffery K Taubenberger

    With great apprehension, the world is now watching the birth of a novel pandemic already causing tremendous suffering, death, and disruption of normal life. Uncertainty and dread are exacerbated by the belief that what we are experiencing is new and mysterious. However, deadly pandemics and disease emergences are not new phenomena: they have been challenging human existence throughout recorded history

    更新日期:2020-06-30
  • Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis of SARS-CoV-2-Related Viruses.
    mBio (IF 6.784) Pub Date : 2020-05-29
    Yongjun Tan,Theresa Schneider,Matthew Leong,L Aravind,Dapeng Zhang

    A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recently identified as the causative agent for the coronavirus disease 2019 (COVID-19) outbreak that has generated a global health crisis. We use a combination of genomic analysis and sensitive profile-based sequence and structure analysis to understand the potential pathogenesis determinants of this virus. As a

    更新日期:2020-06-30
  • Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure.
    mBio (IF 6.784) Pub Date : 2020-06-02
    Min Fu,Xiaowei Zhang,Yiheng Liang,Shouren Lin,Weiping Qian,Shangrong Fan

    Recurrent implantation failure (RIF) refers to repeated failure to become pregnant after transferring embryos with normal morphology. However, the pathogenesis of RIF remains unrevealed, especially for those without any pathological features. In this study, we characterized the vaginal microbiota and metabolomes of patients with unexplained RIF, while patients who achieved clinical pregnancy in the

    更新日期:2020-06-30
  • Rrp6 Regulates Heterochromatic Gene Silencing via ncRNA RUF6 Decay in Malaria Parasites.
    mBio (IF 6.784) Pub Date : 2020-06-02
    Yanting Fan,Shijun Shen,Guiying Wei,Jianxia Tang,Yuemeng Zhao,Fei Wang,Xiaohui He,Gangqiang Guo,Xiaomin Shang,Xinyu Yu,Zhenlin Ma,Xiaoqin He,Meng Liu,Qianshu Zhu,Zhen Le,Gang Wei,Jun Cao,Cizhong Jiang,Qingfeng Zhang

    The heterochromatin environment plays a central role in silencing genes associated with the malaria parasite’s development, survival in the host, and transmission to the mosquito vector. However, the underlying mechanism regulating the dynamic chromatin structure is not understood yet. Here, we have uncovered that Plasmodium falciparum Rrp6, an orthologue of eukaryotic RNA exosome-associated RNase

    更新日期:2020-06-30
  • GRP78 and Integrins Play Different Roles in Host Cell Invasion during Mucormycosis.
    mBio (IF 6.784) Pub Date : 2020-06-02
    Abdullah Alqarihi,Teclegiorgis Gebremariam,Yiyou Gu,Marc Swidergall,Sondus Alkhazraji,Sameh S M Soliman,Vincent M Bruno,John E Edwards,Scott G Filler,Priya Uppuluri,Ashraf S Ibrahim

    Mucormycosis, caused by Rhizopus species, is a life-threatening fungal infection that occurs in patients immunocompromised by diabetic ketoacidosis (DKA), cytotoxic chemotherapy, immunosuppressive therapy, hematologic malignancies, or severe trauma. Inhaled Rhizopus spores cause pulmonary infections in patients with hematologic malignancies, while patients with DKA are much more prone to rhinoorbital/cerebral

    更新日期:2020-06-30
  • Functional Coupling between the Unfolded Protein Response and Endoplasmic Reticulum/Golgi Ca2+-ATPases Promotes Stress Tolerance, Cell Wall Biosynthesis, and Virulence of Aspergillus fumigatus.
    mBio (IF 6.784) Pub Date : 2020-06-02
    Martin Weichert,José Guirao-Abad,Vishukumar Aimanianda,Karthik Krishnan,Christina Grisham,Patrick Snyder,Alex Sheehan,Ruthvik R Abbu,Hong Liu,Scott G Filler,Eric I Gruenstein,Jean-Paul Latgé,David S Askew

    Many species of pathogenic fungi deploy the unfolded protein response (UPR) to expand the folding capacity of the endoplasmic reticulum (ER) in proportion to the demand for virulence-related proteins that traffic through the secretory pathway. Although Ca2+ plays a pivotal role in ER function, the mechanism by which transcriptional upregulation of the protein folding machinery is coordinated with Ca2+

    更新日期:2020-06-30
  • Leishmania Encodes a Bacterium-like 2,4-Dienoyl-Coenzyme A Reductase That Is Required for Fatty Acid β-Oxidation and Intracellular Parasite Survival.
    mBio (IF 6.784) Pub Date : 2020-06-02
    Geo Semini,Daniel Paape,Martin Blume,M Fleur Sernee,Diego Peres-Alonso,Sébastien Calvignac-Spencer,Jörg Döllinger,Stefan Jehle,Eleanor Saunders,Malcolm J McConville,Toni Aebischer

    Leishmania spp. are protozoan parasites that cause a spectrum of important diseases in humans. These parasites develop as extracellular promastigotes in the digestive tract of their insect vectors and as obligate intracellular amastigotes that infect macrophages and other phagocytic cells in their vertebrate hosts. Promastigote-to-amastigote differentiation is associated with marked changes in metabolism

    更新日期:2020-06-30
  • Reversal of Epigenetic Silencing Allows Robust HIV-1 Replication in the Absence of Integrase Function.
    mBio (IF 6.784) Pub Date : 2020-06-02
    Ishak D Irwan,Heather L Karnowski,Hal P Bogerd,Kevin Tsai,Bryan R Cullen

    Integration of the proviral DNA intermediate into the host cell genome normally represents an essential step in the retroviral life cycle. While the reason(s) for this requirement remains unclear, it is known that unintegrated proviral DNA is epigenetically silenced. Here, we demonstrate that human immunodeficiency virus 1 (HIV-1) mutants lacking a functional integrase (IN) can mount a robust, spreading

    更新日期:2020-06-30
  • NOD1/NOD2 and RIP2 Regulate Endoplasmic Reticulum Stress-Induced Inflammation during Chlamydia Infection.
    mBio (IF 6.784) Pub Date : 2020-06-02
    Oanh H Pham,Bokyung Lee,Jasmine Labuda,A Marijke Keestra-Gounder,Mariana X Byndloss,Renée M Tsolis,Stephen J McSorley

    The inflammatory response to Chlamydia infection is likely to be multifactorial and involve a variety of ligand-dependent and -independent recognition pathways. We previously reported the presence of NOD1/NOD2-dependent endoplasmic reticulum (ER) stress-induced inflammation during Chlamydia muridarum infection in vitro, but the relevance of this finding to an in vivo context is unclear. Here, we examined

    更新日期:2020-06-30
  • MicroRNA-325-3p Facilitates Immune Escape of Mycobacterium tuberculosis through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling.
    mBio (IF 6.784) Pub Date : 2020-06-02
    Beibei Fu,Weiwei Xue,Haiwei Zhang,Rui Zhang,Kelly Feldman,Qingting Zhao,Shanfu Zhang,Lei Shi,Krishna Chaitanya Pavani,Weiqi Nian,Xiaoyuan Lin,Haibo Wu

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that poses threats to the public. M. tuberculosis survives in macrophages by escaping from immune surveillance and clearance, which exacerbates the bacterial proliferation. However, the molecular mechanisms of this immune escape have not yet been fully understood. Using multiple cell and mouse models, we found that microRNA-325-3p

    更新日期:2020-06-30
  • Optimal Response to Quorum-Sensing Signals Varies in Different Host Environments with Different Pathogen Group Size.
    mBio (IF 6.784) Pub Date : 2020-06-02
    Liqin Zhou,Leyla Slamti,Didier Lereclus,Ben Raymond

    The persistence of genetic variation in master regulators of gene expression, such as quorum-sensing systems, is hard to explain. Here, we investigated two alternative hypotheses for the prevalence of polymorphic quorum sensing in Gram-positive bacteria, i.e., the use of different signal/receptor pairs (‘pherotypes’) to regulate the same functions. First, social interactions between pherotypes or ‘facultative

    更新日期:2020-06-30
  • Chlorpromazine and Amitriptyline Are Substrates and Inhibitors of the AcrB Multidrug Efflux Pump.
    mBio (IF 6.784) Pub Date : 2020-06-02
    Elizabeth M Grimsey,Chiara Fais,Robert L Marshall,Vito Ricci,Maria Laura Ciusa,Jack W Stone,Alasdair Ivens,Giuliano Malloci,Paolo Ruggerone,Attilio V Vargiu,Laura J V Piddock

    Efflux is an important mechanism in Gram-negative bacteria conferring multidrug resistance. Inhibition of efflux is an encouraging strategy to restore the antibacterial activity of antibiotics. Chlorpromazine and amitriptyline have been shown to behave as efflux inhibitors. However, their mode of action is poorly understood. Exposure of Salmonella enterica serovar Typhimurium and Escherichia coli to

    更新日期:2020-06-30
  • Inhibition of the Super Elongation Complex Suppresses Herpes Simplex Virus Immediate Early Gene Expression, Lytic Infection, and Reactivation from Latency.
    mBio (IF 6.784) Pub Date : 2020-06-09
    Roberto Alfonso-Dunn,Jesse H Arbuckle,Jodi L Vogel,Thomas M Kristie

    Induction of herpes simplex virus (HSV) immediate early (IE) gene transcription promotes the initiation of lytic infection and reactivation from latency in sensory neurons. IE genes are transcribed by the cellular RNA polymerase II (RNAPII) and regulated by multiple transcription factors and coactivators. The HCF-1 cellular coactivator plays a central role in driving IE expression at multiple stages

    更新日期:2020-06-30
  • The Novel J-Domain Protein Mrj1 Is Required for Mitochondrial Respiration and Virulence in Cryptococcus neoformans.
    mBio (IF 6.784) Pub Date : 2020-06-09
    Linda C Horianopoulos,Guanggan Hu,Mélissa Caza,Kerstin Schmitt,Peter Overby,James D Johnson,Oliver Valerius,Gerhard H Braus,James W Kronstad

    The opportunistic fungal pathogen Cryptococcus neoformans must adapt to the mammalian environment to establish an infection. Proteins facilitating adaptation to novel environments, such as chaperones, may be required for virulence. In this study, we identified a novel mitochondrial co-chaperone, Mrj1 (mitochondrial respiration J-domain protein 1), necessary for virulence in C. neoformans. The mrj1Δ

    更新日期:2020-06-30
  • Escherichia coli K-12 Lacks a High-Affinity Assimilatory Cysteine Importer.
    mBio (IF 6.784) Pub Date : 2020-06-09
    Yidan Zhou,James A Imlay

    The most direct route by which microbes might assimilate sulfur would be by importing cysteine. However, alone among the amino acids, cysteine does not have well-characterized importers. We determined that Escherichia coli can rapidly import cysteine, but in our experiments, it did so primarily through the LIV ATP-driven system that is dedicated to branched-chain amino acids. The affinity of this system

    更新日期:2020-06-30
  • Archaeal Chromatin Proteins Cren7 and Sul7d Compact DNA by Bending and Bridging.
    mBio (IF 6.784) Pub Date : 2020-06-09
    Zhenfeng Zhang,Zhengyan Zhan,Bing Wang,Yuanyuan Chen,Xiuqiang Chen,Cuihong Wan,Yu Fu,Li Huang

    Archaeal chromatin proteins Cren7 and Sul7d from Sulfolobus are DNA benders. To better understand their architectural roles in chromosomal DNA organization, we analyzed DNA compaction by Cren7 and Sis7d, a Sul7d family member, from Sulfolobus islandicus at the single-molecule (SM) level by total single-molecule internal reflection fluorescence microscopy (SM-TIRFM) and atomic force microscopy (AFM)

    更新日期:2020-06-30
  • Integrin α5β1, as a Receptor of Fibronectin, Binds the FbaA Protein of Group A Streptococcus To Initiate Autophagy during Infection.
    mBio (IF 6.784) Pub Date : 2020-06-09
    Jiachao Wang,Meiqi Meng,Miao Li,Xiaofei Guan,Jianguo Liu,Xue Gao,Qingqing Sun,Jinquan Li,Cuiqing Ma,Lin Wei

    Group A Streptococcus (GAS), one of the most common extracellular pathogens, has been reported to invade epithelial and endothelial cells. Our results reveal that M1 GAS strain SF370 can be effectively eliminated by respiratory epithelial cells. Emerging evidence indicates that autophagy is an important strategy for nonphagocytes to eliminate intracellular bacteria. Upon pathogen recognition, cell

    更新日期:2020-06-30
  • Pan-GWAS of Streptococcus agalactiae Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation.
    mBio (IF 6.784) Pub Date : 2020-06-09
    Andrea Gori,Odile B Harrison,Ethwako Mlia,Yo Nishihara,Jia Mun Chan,Jacquline Msefula,Macpherson Mallewa,Queen Dube,Todd D Swarthout,Angela H Nobbs,Martin C J Maiden,Neil French,Robert S Heyderman

    Streptococcus agalactiae (group B streptococcus; GBS) is a colonizer of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterized by clonal complexes (CCs) with different invasive potentials. CC17, for example, is a hypervirulent lineage commonly associated with neonatal sepsis and meningitis, while CC1 is less

    更新日期:2020-06-30
  • Basal Body Protein TbSAF1 Is Required for Microtubule Quartet Anchorage to the Basal Bodies in Trypanosoma brucei.
    mBio (IF 6.784) Pub Date : 2020-06-09
    Xiaoduo Dong,Teck Kwang Lim,Qingsong Lin,Cynthia Y He

    Sperm flagellar protein 1 (Spef1, also known as CLAMP) is a microtubule-associated protein involved in various microtubule-related functions from ciliary motility to polarized cell movement and planar cell polarity. In Trypanosoma brucei, the causative agent of trypanosomiasis, a single Spef1 ortholog (TbSpef1) is associated with a microtubule quartet (MtQ), which is in close association with several

    更新日期:2020-06-30
  • Tombusvirus p19 Captures RNase III-Cleaved Double-Stranded RNAs Formed by Overlapping Sense and Antisense Transcripts in Escherichia coli.
    mBio (IF 6.784) Pub Date : 2020-06-09
    Linfeng Huang,Padraig Deighan,Jingmin Jin,Yingxue Li,Hung-Chi Cheung,Elaine Lee,Shirley S Mo,Heather Hoover,Sahar Abubucker,Nancy Finkel,Larry McReynolds,Ann Hochschild,Judy Lieberman

    Antisense transcription is widespread in bacteria. By base pairing with overlapping sense RNAs, antisense RNAs (asRNA) can form double-stranded RNAs (dsRNA), which are cleaved by RNase III, a dsRNA endoribonuclease. The ectopic expression of plant Tombusvirus p19 in Escherichia coli stabilizes ∼21-nucleotide (nt) dsRNA RNase III decay intermediates, which enabled us to characterize otherwise highly

    更新日期:2020-06-30
  • The Nucleoid-Associated Protein GapR Uses Conserved Structural Elements To Oligomerize and Bind DNA.
    mBio (IF 6.784) Pub Date : 2020-06-09
    Rogério F Lourenço,Saumya Saurabh,Jonathan Herrmann,Soichi Wakatsuki,Lucy Shapiro

    Nucleoid-associated proteins (NAPs) are DNA binding proteins critical for the organization and function of the bacterial chromosome. A newly discovered NAP in Caulobacter crescentus, GapR, is thought to facilitate the movement of the replication and transcription machines along the chromosome by stimulating type II topoisomerases to remove positive supercoiling. Here, utilizing genetic, biochemical

    更新日期:2020-06-30
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