Therapeutics and Prevention
Research Article | Therapeutics and PreventionRepurposing Pilocarpine Hydrochloride for Treatment of Candida albicans InfectionsCandida albicans is the most common human fungal pathogen with an estimated crude mortality rate of 40%. The ability of the organism to switch from the yeast to hyphal form and produce biofilms are important virulence factors. C. albicans infections are combatted by the host immune system. However...
Opinion/Hypothesis | Therapeutics and PreventionCD8+ Cytotoxic-T-Lymphocyte Breadth Could Facilitate Early Immune Detection of Immunodeficiency Virus-Derived Epitopes with Limited Expression LevelsCytotoxic-T-lymphocyte (CTL) responses are important to control the replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Accumulating evidence suggests that the ability of a few immunodominant T-cell populations to detect and kill HIV/SIV-infected cells is important in individuals with a protective major histocompatibility complex class I (MHC-I) allele.
Commentary | Therapeutics and PreventionAntibodies Are Major Drivers of Protection against Lethal Aerosol Infection with Highly Pathogenic Burkholderia spp.Burkholderia pseudomallei and Burkholderia mallei are the causative agents of melioidosis and glanders, respectively. There is no vaccine to protect against these highly pathogenic bacteria, and there is concern regarding their emergence as global public health (...
Research Article | Therapeutics and PreventionBurkholderia pseudomallei ΔtonB Δhcp1 Live Attenuated Vaccine Strain Elicits Full Protective Immunity against Aerosolized Melioidosis InfectionIn recent years, an increasing number of melioidosis cases have been reported in several regions where melioidosis is endemic and in areas where melioidosis had not commonly been diagnosed. Currently, the estimated burden of disease is around 165,000 new cases annually, including 89,000 cases that have fatal outcomes. This life-threatening infectious disease is caused by B....
Observation | Therapeutics and PreventionA Novel, Rapid, and Low-Volume Assay for Therapeutic Drug Monitoring of Posaconazole and Other Long-Chain Azole-Class Antifungal DrugsThis work describes an effective assay for TDM of long-chain azole-class antifungal drugs that can be used in diluted human serum samples. This assay will provide a quick, cost-effective method for monitoring concentrations of drugs such as posaconazole that exhibit well-documented pharmacokinetic variability. Our rGO-aptamer assay has the potential to improve health care for those struggling to treat fungal infections in rural or...
Research Article | Therapeutics and PreventionDevelopment of an Opsonophagocytic Killing Assay Using HL-60 Cells for Detection of Functional Antibodies against Streptococcus pyogenesMeasuring functional opsonic antibodies against group A streptococci is an important component of the clinical development path for effective vaccines. Prior studies have used an assay developed over 60 years ago that relied on whole human blood as the source of phagocytes and complement, both of which are critical components of antibody-mediated killing assays. In this study, we adapted an assay that uses the HL-60 human promyelocytic...
Research Article | Therapeutics and PreventionFh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic ShockSepsis is a potentially life-threatening complication of an infection. Sepsis is mostly the consequence of systemic bacterial infections leading to exacerbated activation of immune cells by bacterial products, resulting in enhanced release of inflammatory mediators. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is a critical factor in the pathogenesis of sepsis, which is sensed by Toll-...
Research Article | Therapeutics and PreventionVitamin E Increases Antimicrobial Sensitivity by Inhibiting Bacterial Lipocalin Antibiotic BindingBacteria exposed to stress mediated by sublethal antibiotic concentrations respond by adaptive mechanisms leading to an overall increase of antibiotic resistance. One of these mechanisms involves the release of bacterial proteins called lipocalins, which have the ability to sequester antibiotics in the extracellular space before they reach bacterial cells. We speculated that interfering with lipocalin-mediated antibiotic binding could...
Research Article | Therapeutics and PreventionAcquired Nisin Resistance in Staphylococcus aureus Involves Constitutive Activation of an Intrinsic Peptide Antibiotic Detoxification ModuleNIS and related bacteriocins are of interest as candidates for the treatment of human infections caused by Gram-positive pathogens such as Staphylococcus aureus. An important liability of NIS in this regard is the ease with which S. aureus acquires resistance. Here we establish that this organism...
Research Article | Therapeutics and PreventionImproving Our Understanding of Salmonella enterica Serovar Paratyphi B through the Engineering and Testing of a Live Attenuated Vaccine StrainWe developed a live attenuated Salmonella enterica serovar Paratyphi B vaccine that conferred protection in mice against challenge with S. Paratyphi B sensu stricto and S. Paratyphi B Java, which are the causes of enteric fever and gastroenteritis, respectively. Currently, the incidence of invasive S. Paratyphi B sensu stricto...