Therapeutics and Prevention
Research Article | Therapeutics and PreventionThe Aminoalkylindole BML-190 Negatively Regulates Chitosan Synthesis via the Cyclic AMP/Protein Kinase A1 Pathway in Cryptococcus neoformansCryptococcus neoformans is a fungal pathogen that kills ∼200,000 people every year. The cell wall is an essential organelle that protects fungi from the environment. Chitosan, the deacetylated form of chitin, has been shown to be an essential component of the cryptococcal cell wall during infection of a mammalian host. In this study, we screened a set of 480 compounds...
Editor's Pick Research Article | Therapeutics and PreventionA Mechanosensitive Channel Governs Lipid Flippase-Mediated Echinocandin Resistance in Cryptococcus neoformansCryptococcus neoformans is the leading cause of fungal meningitis, accounting for ∼15% of HIV/AIDS-related deaths, but treatment options for cryptococcosis are limited. Echinocandins are the newest fungicidal drug class introduced but are ineffective in treating cryptococcosis. Our previous study identified the lipid flippase subunit Cdc50 as a contributor to...
Research Article | Therapeutics and PreventionFluconazole Monotherapy Is a Suboptimal Option for Initial Treatment of Cryptococcal Meningitis Because of Emergence of ResistanceCryptococcal meningitis is a lethal disease with few treatment options. The incidence remains high and intricately linked with the HIV/AIDS epidemic. In many parts of the world, fluconazole is the only agent that is available for the initial treatment of cryptococcal meningitis despite considerable evidence that it is associated with suboptimal microbiological and clinical outcomes. Fluconazole has a fungistatic mode of action: it...
Research Article | Therapeutics and PreventionA Multicomponent Vaccine Provides Immunity against Local and Systemic Infections by Group A Streptococcus across SerotypesGAS is among the most common human pathogens and causes a wide variety of diseases, likely more than any other microorganism. The diverse clinical manifestations of GAS may be attributable to its large repertoire of virulence factors that are selectively and synergistically involved in streptococcal pathogenesis. To date, GAS vaccines have not been successful due to multiple serotypes and postinfection sequelae associated with...
Research Article | Therapeutics and PreventionMultidrug Resistance in Neisseria gonorrhoeae: Identification of Functionally Important Residues in the MtrD Efflux ProteinWith over 78 million new infections globally each year, gonorrhea remains a frustratingly common infection. Continuous development and spread of antimicrobial-resistant strains of Neisseria gonorrhoeae, the causative agent of gonorrhea, have posed a serious threat to public health. One of the mechanisms in...
Research Article | Therapeutics and PreventionTranscriptomic Signatures Predict Regulators of Drug Synergy and Clinical Regimen Efficacy against TuberculosisMultidrug combination therapy is an important strategy for treating tuberculosis, the world’s deadliest bacterial infection. Long treatment durations and growing rates of drug resistance have created an urgent need for new approaches to prioritize effective drug regimens. Hence, we developed a computational model called INDIGO-MTB that identifies synergistic drug regimens from an immense set of possible drug combinations using the...
Research Article | Therapeutics and PreventionPreclinical Efficacy of a Lipooligosaccharide Peptide Mimic Candidate Gonococcal VaccineNeisseria gonorrhoeae has become resistant to most antibiotics. The incidence of gonorrhea is also sharply increasing. A safe and effective antigonococcal vaccine is urgently needed. Lipooligosaccharide (LOS), the most abundant outer membrane molecule, is indispensable for gonococcal pathogenesis. A glycan epitope on LOS that is recognized by monoclonal antibody (MAb...
Research Article | Therapeutics and PreventionFcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific AntibodiesThere is a pressing need for next-generation influenza vaccine strategies that are better able to manage antigenic drift and the cocirculation of multiple drift variants and that consistently improve vaccine effectiveness. Influenza virus NA is a key target antigen as a component of a next-generation vaccine in the influenza field, with evidence for a role in protective immunity in humans. However, mechanisms of protection provided by...
Research Article | Therapeutics and PreventionAttenuation of Live-Attenuated Yellow Fever 17D Vaccine Virus Is Localized to a High-Fidelity Replication ComplexLive-attenuated viral vaccines are highly safe and efficacious but represent complex and often multigenic attenuation mechanisms. Most of these vaccines have been generated empirically by serial passaging of a wild-type (WT) virus in cell culture. One of the safest and most effective live-attenuated vaccines is yellow fever (YF) virus strain 17D, which has been used for over 80 years to control YF disease. The availability of the WT...
Research Article | Therapeutics and PreventionHuman VH1-69 Gene-Encoded Human Monoclonal Antibodies against Staphylococcus aureus IsdB Use at Least Three Distinct Modes of Binding To Inhibit Bacterial Growth and PathogenesisThe human pathogen Staphylococcus aureus causes a wide range of infections, including skin abscesses and sepsis. There is currently no licensed vaccine to prevent S. aureus infection, and its treatment has become increasingly difficult due to antibiotic resistance. One potential way to inhibit...