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Therapeutics and Prevention

  • Open Access
    Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial
    Research Article | Therapeutics and Prevention
    Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial

    Antibody-dependent cellular cytotoxicity (ADCC) correlated with a reduced risk of infection from HIV-1 in the RV144 vaccine trial, the only HIV-1 vaccine trial to date to show any efficacy. Antibodies specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (cluster A region) were induced in the RV144 trial and their ADCC activities were implicated in the vaccine efficacy. We present structural analyses of the...

    William D. Tolbert, Verna Van, Rebekah Sherburn, Marina Tuyishime, Fang Yan, Dung N. Nguyen, Sherry Stanfield-Oakley, David Easterhoff, Mattia Bonsignori, Barton F. Haynes, M. Anthony Moody, Krishanu Ray, Guido Ferrari, George K. Lewis, Marzena Pazgier
  • Open Access
    A Physiological Basis for Nonheritable Antibiotic Resistance
    Minireview | Therapeutics and Prevention
    A Physiological Basis for Nonheritable Antibiotic Resistance

    Antibiotics constitute one of the cornerstones of modern medicine. However, individuals may succumb to a bacterial infection if a pathogen survives exposure to antibiotics. The ability of bacteria to survive bactericidal antibiotics results from genetic changes in the preexisting bacterial genome, from the acquisition of genes from other organisms, and from nonheritable phenomena that give rise to antibiotic tolerance. Nonheritable...

    Mauricio H. Pontes, Eduardo A. Groisman
  • Open Access
    Convergent Evolution of Neutralizing Antibodies to <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span> γ-Hemolysin C That Recognize an Immunodominant Primary Sequence-Dependent B-Cell Epitope
    Research Article | Therapeutics and Prevention
    Convergent Evolution of Neutralizing Antibodies to Staphylococcus aureus γ-Hemolysin C That Recognize an Immunodominant Primary Sequence-Dependent B-Cell Epitope

    Staphylococcus aureus infection is a major public health threat in part due to the spread of antibiotic resistance and repeated failures to develop a protective vaccine. Infection is associated with production of virulence factors that include exotoxins that attack host barriers and cellular defenses, such as the leukocidin (Luk) family of bicomponent pore-forming...

    David N. Hernandez, Kayan Tam, Bo Shopsin, Emily E. Radke, Karen Law, Timothy Cardozo, Victor J. Torres, Gregg J. Silverman
  • Open Access
    Chlorpromazine and Amitriptyline Are Substrates and Inhibitors of the AcrB Multidrug Efflux Pump
    Research Article | Therapeutics and Prevention
    Chlorpromazine and Amitriptyline Are Substrates and Inhibitors of the AcrB Multidrug Efflux Pump

    Efflux pumps of the resistance nodulation-cell division (RND) superfamily are major contributors to multidrug resistance for most of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae,...

    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
  • Open Access
    Reply to Siniorakis et al., “COVID-19 Interference with Renin-Angiotensin System in the Context of Heart Failure”
    Author Reply | Therapeutics and Prevention
    Reply to Siniorakis et al., “COVID-19 Interference with Renin-Angiotensin System in the Context of Heart Failure”
    David S. Fedson, Steven M. Opal, Ole Martin Rordam
  • Open Access
    Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets
    Research Article | Therapeutics and Prevention
    Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets

    The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly...

    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
  • Open Access
    Mutations in <em>TAC1B</em>: a Novel Genetic Determinant of Clinical Fluconazole Resistance in <span class="named-content genus-species" id="named-content-1">Candida auris</span>
    Editor's Pick Research Article | Therapeutics and Prevention
    Mutations in TAC1B: a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris

    Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and to be commonly resistant to antifungals. While the vast majority of clinical C. auris isolates are highly resistant to fluconazole, an essential part of the...

    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
  • Open Access
    Glycerol Monolaurate, an Analogue to a Factor Secreted by <em>Lactobacillus</em>, Is Virucidal against Enveloped Viruses, Including HIV-1
    Research Article | Therapeutics and Prevention
    Glycerol Monolaurate, an Analogue to a Factor Secreted by Lactobacillus, Is Virucidal against Enveloped Viruses, Including HIV-1

    A total of 340 million sexually transmitted infections (STIs) are acquired each year. Antimicrobial agents that target multiple infectious pathogens are ideal candidates to reduce the number of newly acquired STIs. The antimicrobial and immunoregulatory properties of GML make it an excellent candidate to fit this critical need. Previous studies established the safety profile and antibacterial activity of GML against both Gram-positive...

    Jennifer L. Welch, Jinhua Xiang, Chioma M. Okeoma, Patrick M. Schlievert, Jack T. Stapleton
  • Open Access
    Optimization of an Experimental Vaccine To Prevent <span class="named-content genus-species" id="named-content-1">Escherichia coli</span> Urinary Tract Infection
    Research Article | Therapeutics and Prevention
    Optimization of an Experimental Vaccine To Prevent Escherichia coli Urinary Tract Infection

    Urinary tract infections (UTI) are among the most common bacterial infection in humans, affecting half of all women at least once during their lifetimes. The rise in antibiotic resistance and health care costs emphasizes the need to develop a vaccine against the most common UTI pathogen, Escherichia coli. Vaccinating mice intranasally with a detoxified heat-labile...

    Valerie S. Forsyth, Stephanie D. Himpsl, Sara N. Smith, Christina A. Sarkissian, Laura A. Mike, Jolie A. Stocki, Anna Sintsova, Christopher J. Alteri, Harry L. T. Mobley
  • Open Access
    Targeting Hidden Pathogens: Cell-Penetrating Enzybiotics Eradicate Intracellular Drug-Resistant <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span>
    Research Article | Therapeutics and Prevention
    Targeting Hidden Pathogens: Cell-Penetrating Enzybiotics Eradicate Intracellular Drug-Resistant Staphylococcus aureus

    The increasing prevalence of antibiotic-resistant bacteria is one of the most urgent problems of our time. Staphylococcus aureus is an important human pathogen that has acquired several mechanisms to evade antibiotic treatment. In addition, S. aureus is able to invade and persist within human cells...

    Christian Röhrig, Markus Huemer, Dominique Lorgé, Samuel Luterbacher, Preeda Phothaworn, Christopher Schefer, Anna M. Sobieraj, Léa V. Zinsli, Srikanth Mairpady Shambat, Nadja Leimer, Anja P. Keller, Fritz Eichenseher, Yang Shen, Sunee Korbsrisate, Annelies S. Zinkernagel, Martin J. Loessner, Mathias Schmelcher

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