Therapeutics and Prevention
Research Article | Therapeutics and PreventionIdentification of a Shared Cytochrome p4502E1 Epitope Found in Anesthetic Drug-Induced and Viral HepatitisDrug-induced hepatitis is the leading reason that an approved drug is removed from the commercial market. Halogenated anesthetics can induce hepatitis in susceptible persons, and cytochrome p4502E1 (CYP2E1) enzymes responsible for their metabolism induce antibodies in addition to hepatitis. CYP2E1 antibodies detected in anesthetic hepatitis patients have been detected in patients with viral hepatitis, suggesting that these different...
Research Article | Therapeutics and PreventionA Computational Modeling Approach Predicts Interaction of the Antifungal Protein AFP from Aspergillus giganteus with Fungal Membranes via Its γ-Core MotifFungal pathogens pose a serious danger to human welfare since they kill more people per year than malaria or tuberculosis and are responsible for crop losses worldwide. The treatment of fungal infections is becoming more complicated as fungi develop resistances against commonly used fungicides. Therefore, discovery and development of novel antifungal agents are of utmost importance.
Research Article | Therapeutics and PreventionTRAIL (CD253) Sensitizes Human Airway Epithelial Cells to Toxin-Induced Cell DeathRicin toxin is a biothreat agent that is particularly damaging to lung tissue following inhalation. A hallmark of ricin exposure is widespread inflammation and concomitant destruction of the airway epithelium. In this study, we investigated the possible interaction between ricin and known proinflammatory cytokines associated with lung tissue. Using an established human airway epithelial cell line, we demonstrate that epithelial cell...
Observation | Therapeutics and PreventionMCR-1 Confers Cross-Resistance to Bacitracin, a Widely Used In-Feed AntibioticPolymyxins (e.g., colistin) are the drugs of last resort to treat multidrug-resistant infections in humans. To control mobile colistin resistance, there is a worldwide trend to limit colistin use in animal production. However, simply limiting colistin use in animal production may still not effectively mitigate colistin resistance due to an overlooked non-colistin usage factor(s). Using controlled systems, in this study, we observed that...
Research Article | Therapeutics and PreventionDifferential Transmission of Antiviral Drug-Resistant Chikungunya Viruses by Aedes MosquitoesBecause of its global reemergence and unusual morbidities associated with infection, the chikungunya virus (CHIKV) has become a substantial public health problem. However, no antivirals are currently available to treat CHIKV infections. If antiviral drugs will prove to be efficient to treat CHIKV-infected patients, it will be essential to understand if drug-resistant viruses can be transmitted from one human to another by the mosquito....
Research Article | Therapeutics and PreventionTwo Vaccines for Staphylococcus aureus Induce a B-Cell-Mediated Immune ResponseStaphylococcus aureus causes severe disease in humans for which no licensed vaccine exists. A novel vaccine is in development that targets multiple elements of the bacteria since single-component vaccines have not shown efficacy to date. How these multiple components alter the immune response raised by the vaccine is not well studied. We found that the addition of two...
Research Article | Therapeutics and PreventionPotential Coverage of the 4CMenB Vaccine against Invasive Serogroup B Neisseria meningitidis Isolated from 2009 to 2013 in the Republic of IrelandThe meningococcal antigen typing system (MATS) is an enzyme-linked immunosorbent assay (ELISA) that measures both the levels of expression and the immune reactivity of the three recombinant 4CMenB antigens. Together with PorA variable-region sequence data, this system provides an estimation of how susceptible MenB isolates are to killing by 4CMenB vaccine-induced antibodies. Assays based on subcapsular antigen phenotype analyses, such...
Editor's Pick Research Article | Therapeutics and PreventionSpleen Tyrosine Kinase Inhibitor TAK-659 Prevents Splenomegaly and Tumor Development in a Murine Model of Epstein-Barr Virus-Associated LymphomaThe novel SYK and FLT3 inhibitor TAK-659 prevents the enlargement of spleen and tumor development in a mouse model of EBV-associated lymphoma by counteracting the activation of cellular kinase SYK through the viral LMP2A gene by inducing cell death in tumor cells but not in nontumor cells. These findings indicate that TAK-659 may be a very effective nontoxic therapeutic molecule especially for EBV-positive hematologic malignancies....
Research Article | Therapeutics and PreventionAminoglycoside Heteroresistance in Acinetobacter baumannii AB5075Acinetobacter baumannii has become an important pathogen in hospitals worldwide, where the incidence of these infections has been increasing. A. baumannii infections have become exceedingly difficult to treat due to a rapid increase in the frequency of multidrug- and pan-resistant isolates. This has...
Research Article | Therapeutics and PreventionMechanism of High-Level Daptomycin Resistance in Corynebacterium striatumAntimicrobial resistance threatens the efficacy of antimicrobial treatment options, including last-line-of-defense drugs. Understanding how this resistance develops can help direct antimicrobial stewardship efforts and is critical to designing the next generation of antimicrobial therapies. Here we determine how Corynebacterium striatum, a skin commensal and...