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Therapeutics and Prevention

  • Open Access
    HIV Drugs Inhibit Transfer of Plasmids Carrying Extended-Spectrum β-Lactamase and Carbapenemase Genes
    Research Article | Therapeutics and Prevention
    HIV Drugs Inhibit Transfer of Plasmids Carrying Extended-Spectrum β-Lactamase and Carbapenemase Genes

    More and more bacterial infections are becoming resistant to antibiotics. This has made treatment of many infections very difficult. One of the reasons this is such a large problem is that bacteria are able to share their genetic material with other bacteria, and these shared genes often include resistance to a variety of antibiotics, including some of our drugs of last resort. We are addressing this problem by using a fluorescence-...

    Michelle M. C. Buckner, M. Laura Ciusa, Richard W. Meek, Alice R. Moorey, Gregory E. McCallum, Emma L. Prentice, Jeremy P. Reid, Luke J. Alderwick, Alessandro Di Maio, Laura J. V. Piddock
  • Open Access
    A Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing
    Research Article | Therapeutics and Prevention
    A Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing

    Prompt and effective antimicrobial therapy is crucial for the management of patients with severe bacterial infections but is becoming increasingly difficult to provide due to emerging antibiotic resistance. The traditional methods for antibiotic susceptibility testing (AST) used in most clinical laboratories are reliable but slow with turnaround times of 2 to 3 days, which necessitates the use of empirical therapy with broad-spectrum...

    Pikkei Wistrand-Yuen, Christer Malmberg, Nikos Fatsis-Kavalopoulos, Moritz Lübke, Thomas Tängdén, Johan Kreuger
  • Open Access
    Rapid Freezing Enables Aminoglycosides To Eradicate Bacterial Persisters via Enhancing Mechanosensitive Channel MscL-Mediated Antibiotic Uptake
    Research Article | Therapeutics and Prevention
    Rapid Freezing Enables Aminoglycosides To Eradicate Bacterial Persisters via Enhancing Mechanosensitive Channel MscL-Mediated Antibiotic Uptake

    Antibiotics have long been used to successfully kill bacterial pathogens, but antibiotic resistance/tolerance usually has led to the failure of antibiotic therapy, and it has become a severe threat to human health. How to improve the efficacy of existing antibiotics is of importance for combating antibiotic-resistant/tolerant pathogens. Here, we report that 10-s rapid freezing with liquid nitrogen dramatically enhanced the bactericidal...

    Yanna Zhao, Boyan Lv, Fengqi Sun, Jiafeng Liu, Yan Wang, Yuanyuan Gao, Feng Qi, Zengyi Chang, Xinmiao Fu
  • Open Access
    Data Mining a Medieval Medical Text Reveals Patterns in Ingredient Choice That Reflect Biological Activity against Infectious Agents
    Research Article | Therapeutics and Prevention
    Data Mining a Medieval Medical Text Reveals Patterns in Ingredient Choice That Reflect Biological Activity against Infectious Agents

    We used established methodologies from network science to identify patterns in medicinal ingredient combinations in a key medieval text, the 15th-century Lylye of Medicynes, focusing on recipes for topical treatments for symptoms of microbial infection. We conducted experiments screening the antimicrobial activity of selected ingredients. These experiments revealed interesting examples of ingredients that potentiated or...

    Erin Connelly, Charo I. del Genio, Freya Harrison
  • Open Access
    Novel Cassette Assay To Quantify the Outer Membrane Permeability of Five β-Lactams Simultaneously in Carbapenem-Resistant <em>Klebsiella pneumoniae</em> and <em>Enterobacter cloacae</em>
    Research Article | Therapeutics and Prevention
    Novel Cassette Assay To Quantify the Outer Membrane Permeability of Five β-Lactams Simultaneously in Carbapenem-Resistant Klebsiella pneumoniae and Enterobacter cloacae

    Antimicrobial resistance is causing a global human health crisis and is affecting all antibiotic classes. While β-lactams have been commonly used against susceptible isolates of Klebsiella pneumoniae and Enterobacter cloacae, carbapenem-resistant isolates are spreading worldwide and pose substantial...

    Tae Hwan Kim, Xun Tao, Bartolome Moya, Yuanyuan Jiao, Kari B. Basso, Jieqiang Zhou, Yinzhi Lang, Dhruvitkumar S. Sutaria, Alexandre P. Zavascki, Afonso L. Barth, Stephanie M. Reeve, Herbert P. Schweizer, Deanna Deveson Lucas, John D. Boyce, Robert A. Bonomo, Richard E. Lee, Beom Soo Shin, Arnold Louie, George L. Drusano, Jürgen B. Bulitta
  • Open Access
    Hijacking the Fusion Complex of Human Parainfluenza Virus as an Antiviral Strategy
    Research Article | Therapeutics and Prevention
    Hijacking the Fusion Complex of Human Parainfluenza Virus as an Antiviral Strategy

    Paramyxoviruses, including human parainfluenza virus type 3, are internalized into host cells by fusion between viral and target cell membranes. The receptor binding protein, hemagglutinin-neuraminidase (HN), upon binding to its cell receptor, triggers conformational changes in the fusion protein (F). This action of HN activates F to reach its fusion-competent state. Using small molecules that interact with HN, we can induce the...

    T. C. Marcink, E. Yariv, K. Rybkina, V. Más, F. T. Bovier, A. des Georges, A. L. Greninger, C. A. Alabi, M. Porotto, N. Ben-Tal, A. Moscona
  • Open Access
    Reducing <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span> Virulence through Targeted Dysregulation of the Conidiation Pathway
    Research Article | Therapeutics and Prevention
    Reducing Aspergillus fumigatus Virulence through Targeted Dysregulation of the Conidiation Pathway

    The mold Aspergillus fumigatus reproduces by the production of airborne spores (conidia), a process termed conidiation. In immunocompromised individuals, inhaled A. fumigatus conidia can germinate and form filaments that penetrate and damage lung tissues; however, conidiation does not occur during...

    James I. P. Stewart, Vinicius M. Fava, Joshua D. Kerkaert, Adithya S. Subramanian, Fabrice N. Gravelat, Melanie Lehoux, P. Lynne Howell, Robert A. Cramer, Donald C. Sheppard
  • Open Access
    Phage Resistance in Multidrug-Resistant <span class="named-content genus-species" id="named-content-1">Klebsiella pneumoniae</span> ST258 Evolves via Diverse Mutations That Culminate in Impaired Adsorption
    Research Article | Therapeutics and Prevention
    Phage Resistance in Multidrug-Resistant Klebsiella pneumoniae ST258 Evolves via Diverse Mutations That Culminate in Impaired Adsorption

    The therapeutic use of bacteriophage (phage) is garnering renewed interest in the setting of difficult-to-treat infections. Phage resistance is one major limitation of phage therapy; therefore, developing effective strategies to avert or lessen its impact is critical. Characterization of in vitro phage resistance may be an important first step in evaluating the relative likelihood with which phage-resistant populations emerge,...

    Shayla Hesse, Manoj Rajaure, Erin Wall, Joy Johnson, Valery Bliskovsky, Susan Gottesman, Sankar Adhya
  • Open Access
    <span class="named-content genus-species" id="named-content-1">Plasmodium falciparum</span> Resistance to a Lead Benzoxaborole Due to Blocked Compound Activation and Altered Ubiquitination or Sumoylation
    Research Article | Therapeutics and Prevention
    Plasmodium falciparum Resistance to a Lead Benzoxaborole Due to Blocked Compound Activation and Altered Ubiquitination or Sumoylation

    Benzoxaboroles are under study as potential new drugs to treat malaria. One benzoxaborole, AN13762, has potent activity and promising features, but its mechanisms of action and resistance are unknown. To gain insights into these mechanisms, we cultured malaria parasites with nonlethal concentrations of AN13762 and generated parasites with varied levels of resistance. Parasites with low-level resistance had mutations in PfPARE, which...

    Kirthana M. V. Sindhe, Wesley Wu, Jenny Legac, Yong-Kang Zhang, Eric E. Easom, Roland A. Cooper, Jacob J. Plattner, Yvonne R. Freund, Joseph L. DeRisi, Philip J. Rosenthal
  • Open Access
    The O-Antigen Epitope Governs Susceptibility to Colistin in <span class="named-content genus-species" id="named-content-1">Salmonella enterica</span>
    Research Article | Therapeutics and Prevention
    The O-Antigen Epitope Governs Susceptibility to Colistin in Salmonella enterica

    Some serovars of Salmonella, namely, those belonging to group D, appear to show a degree of intrinsic resistance to colistin. This observed intrinsic colistin resistance is of concern since this last-resort drug might no longer be effective for treating severe human infections with the most common Salmonella serovar, Salmonella enterica serovar...

    Vito Ricci, Dexian Zhang, Christopher Teale, Laura J. V. Piddock

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