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Host-Microbe Biology

  • Open Access
    A Small-Molecule Modulator of Metal Homeostasis in Gram-Positive Pathogens
    Research Article | Host-Microbe Biology
    A Small-Molecule Modulator of Metal Homeostasis in Gram-Positive Pathogens

    Staphylococcus aureus is a leading agent of antibiotic-resistant bacterial infections in the world. S. aureus tightly controls metal homeostasis during infection, and disruption of metal uptake systems impairs staphylococcal virulence. We identified small molecules that interfere with metal handling...

    Lillian J. Juttukonda, William N. Beavers, Daisy Unsihuay, Kwangho Kim, Gleb Pishchany, Kyle J. Horning, Andy Weiss, Hassan Al-Tameemi, Jeffrey M. Boyd, Gary A. Sulikowski, Aaron B. Bowman, Eric P. Skaar
  • Open Access
    DDX56 Binds to Chikungunya Virus RNA To Control Infection
    Research Article | Host-Microbe Biology
    DDX56 Binds to Chikungunya Virus RNA To Control Infection

    Arthropod-borne viruses are diverse pathogens and include the emerging virus chikungunya virus, which is associated with human disease. Through genetic screening, we found that the conserved RNA binding protein DDX56 is antiviral against chikungunya virus in insects and humans. DDX56 relocalizes from the nucleus to the cytoplasm, where it binds to a stem-loop in the viral genome and destabilizes incoming genomes. Thus, DDX56 is an...

    Frances Taschuk, Iulia Tapescu, Ryan H. Moy, Sara Cherry
  • Open Access
    Estimation of Full-Length TprK Diversity in <span class="named-content genus-species" id="named-content-1">Treponema pallidum</span> subsp. <em>pallidum</em>
    Research Article | Host-Microbe Biology
    Estimation of Full-Length TprK Diversity in Treponema pallidum subsp. pallidum

    Syphilis continues to be a significant public health issue in both low- and high-income countries, including the United States where the rate of syphilis infection has increased over the past 5 years. Treponema pallidum subsp. pallidum, the causative agent of syphilis, carries the outer membrane protein TprK that undergoes segmental gene conversion to...

    Amin Addetia, Michelle J. Lin, Quynh Phung, Hong Xie, Meei-Li Huang, Giulia Ciccarese, Ivano Dal Conte, Marco Cusini, Francesco Drago, Lorenzo Giacani, Alexander L. Greninger
  • Open Access
    Population Analysis of <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span> Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia
    Research Article | Host-Microbe Biology
    Population Analysis of Staphylococcus aureus Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia

    Staphylococcus aureus is an important human and animal pathogen associated with an array of diseases, including life-threatening necrotizing pneumonia and infective endocarditis. The success of S. aureus as a pathogen has been linked in part to its ability to manipulate the host immune response...

    Manouk Vrieling, Stephen W. Tuffs, Gonzalo Yebra, Marleen Y. van Smoorenburg, Joana Alves, Amy C. Pickering, Joo Youn Park, Nogi Park, David E. Heinrichs, Lindert Benedictus, Timothy Connelley, Keun Seok Seo, John K. McCormick, J. Ross Fitzgerald
  • Open Access
    HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation
    Research Article | Host-Microbe Biology
    HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation

    The ubiquitin-proteasome system (UPS) is essential for the degradation of damaged proteins, which takes place in the proteasome. Upon activation by cytokines, the catalytic subunits of the proteasome are replaced by distinct isoforms resulting in the formation of an immunoproteasome (iProteasome). iProteasome generates peptides used by major histocompatibility complex class I (MHC-I) for antigen presentation and is essential for immune...

    Yang Yang, Weiyong Liu, Dan Hu, Rui Su, Man Ji, Yuqing Huang, Muhammad Adnan Shereen, Xiaodi Xu, Zhen Luo, Qi Zhang, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu
  • Open Access
    Heterologous Production of 1-Tuberculosinyladenosine in <span class="named-content genus-species" id="named-content-1">Mycobacterium kansasii</span> Models Pathoevolution towards the Transcellular Lifestyle of <span class="named-content genus-species" id="named-content-2">Mycobacterium tuberculosis</span>
    Research Article | Host-Microbe Biology
    Heterologous Production of 1-Tuberculosinyladenosine in Mycobacterium kansasii Models Pathoevolution towards the Transcellular Lifestyle of Mycobacterium tuberculosis

    This work sheds light on the role of the lipid 1-tuberculosinyladenosine in the evolution of an environmental ancestor to M. tuberculosis. On a larger scale, it reinforces the importance of horizontal gene transfer in bacterial evolution and examines novel models and methods to provide a better understanding of the subtle effects of individual...

    Marwan Ghanem, Jean-Yves Dubé, Joyce Wang, Fiona McIntosh, Daniel Houle, Pilar Domenech, Michael B. Reed, Sahadevan Raman, Jeffrey Buter, Adriaan J. Minnaard, D. Branch Moody, Marcel A. Behr
  • Open Access
    Antibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier
    Observation | Host-Microbe Biology
    Antibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier

    HIV-1 can cross the blood-brain barrier (BBB) to penetrate the brain and infect target cells, causing neurocognitive disorders as a result of neuroinflammation and brain damage. The HIV-1 envelope spike gp160 is partially required for viral transcytosis across the BBB endothelium. But do antibodies developing in infected individuals and targeting the HIV-1 gp160 glycoproteins block HIV-1 transcytosis through the BBB? We addressed this...

    Valérie Lorin, Anne Danckaert, Françoise Porrot, Olivier Schwartz, Philippe V. Afonso, Hugo Mouquet
  • Open Access
    IP<sub>7</sub>-SPX Domain Interaction Controls Fungal Virulence by Stabilizing Phosphate Signaling Machinery
    Research Article | Host-Microbe Biology
    IP7-SPX Domain Interaction Controls Fungal Virulence by Stabilizing Phosphate Signaling Machinery

    Invasive fungal diseases pose a serious threat to human health globally with >1.5 million deaths occurring annually, 180,000 of which are attributable to the AIDS-related pathogen, Cryptococcus neoformans. Here, we demonstrate that interaction of the inositol pyrophosphate, IP7, with the CDK inhibitor protein, Pho81, is instrumental in promoting fungal...

    Desmarini Desmarini, Sophie Lev, David Furkert, Ben Crossett, Adolfo Saiardi, Keren Kaufman-Francis, Cecilia Li, Tania C. Sorrell, Lorna Wilkinson-White, Jacqueline Matthews, Dorothea Fiedler, Julianne Teresa Djordjevic
  • Open Access
    SARS-CoV-2 Is Restricted by Zinc Finger Antiviral Protein despite Preadaptation to the Low-CpG Environment in Humans
    Research Article | Host-Microbe Biology
    SARS-CoV-2 Is Restricted by Zinc Finger Antiviral Protein despite Preadaptation to the Low-CpG Environment in Humans

    Although interferons inhibit SARS-CoV-2 and have been evaluated for treatment of coronavirus disease 2019 (COVID-19), the most effective types and antiviral effectors remain to be defined. Here, we show that IFN-γ is particularly potent in restricting SARS-CoV-2 and in inducing expression of the antiviral factor ZAP in human lung cells. Knockdown experiments revealed that endogenous ZAP significantly restricts SARS-CoV-2. We further...

    Rayhane Nchioua, Dorota Kmiec, Janis A. Müller, Carina Conzelmann, Rüdiger Groß, Chad M. Swanson, Stuart J. D. Neil, Steffen Stenger, Daniel Sauter, Jan Münch, Konstantin M. J. Sparrer, Frank Kirchhoff
  • Open Access
    Higher-Order Interactions Dampen Pairwise Competition in the Zebrafish Gut Microbiome
    Editor's Pick Research Article | Host-Microbe Biology
    Higher-Order Interactions Dampen Pairwise Competition in the Zebrafish Gut Microbiome

    Understanding the rules governing the composition of the diverse microbial communities that reside in the vertebrate gut environment will enhance our ability to manipulate such communities for therapeutic ends. Synthetic microbial communities, assembled from specific combinations of microbial species in germfree animals, allow investigation of the fundamental question of whether multispecies community composition can be predicted solely...

    Deepika Sundarraman, Edouard A. Hay, Dylan M. Martins, Drew S. Shields, Noah L. Pettinari, Raghuveer Parthasarathy

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