Therapeutics and Prevention
Research Article | Therapeutics and PreventionPhage-Antibiotic Synergy Is Driven by a Unique Combination of Antibacterial Mechanism of Action and StoichiometryBacteriophage (phage) therapy is a promising approach to combat the rise of multidrug-resistant bacteria. Currently, the preferred clinical modality is to pair phage with an antibiotic, a practice thought to improve efficacy. However, antagonism between phage and antibiotics has been reported, the choice of phage and antibiotic is not often empirically determined, and the effect of the host factors on the effectiveness is unknown. Here...
Research Article | Therapeutics and PreventionAn Entry-Triggering Protein of Ehrlichia Is a New Vaccine Candidate against Tick-Borne Human Monocytic EhrlichiosisThe incidence of tick-borne diseases has risen dramatically in the past two decades and continues to rise. Discovered in 1986 and designated a nationally notifiable disease in 1998 by the Centers for Disease Control and Prevention, human monocytic ehrlichiosis, which is caused by the bacterium Ehrlichia chaffeensis, is one of the most prevalent, life-threatening,...
Research Article | Therapeutics and PreventionAn Antivirulence Approach for Preventing Cryptococcus neoformans from Crossing the Blood-Brain Barrier via Novel Natural Product Inhibitors of a Fungal MetalloproteaseFungal infections like cryptococcal meningitis are difficult to resolve because of the limited therapies available. The small arsenal of antifungal drugs reflect the difficulty in finding available targets in fungi because like mammalian cells, fungi are eukaryotes. The limited efficacy, toxicity, and rising resistance of antifungals contribute to the high morbidity and mortality of fungal infections and further underscore the dire but...
Research Article | Therapeutics and PreventionNew Multidrug Efflux Inhibitors for Gram-Negative BacteriaMultidrug-resistant Gram-negative bacteria pose a serious threat to human and animal health. Molecules that inhibit multidrug efflux offer an alternative approach to resolving the challenges caused by antibiotic resistance, by potentiating the activity of old, licensed, and new antibiotics. We have developed, validated, and implemented a high-throughput screen and used it to identify efflux inhibitors from two compound libraries...
Research Article | Therapeutics and PreventionRecognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine TrialAntibody-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...
Minireview | Therapeutics and PreventionA Physiological Basis for Nonheritable Antibiotic ResistanceAntibiotics 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...
Research Article | Therapeutics and PreventionConvergent Evolution of Neutralizing Antibodies to Staphylococcus aureus γ-Hemolysin C That Recognize an Immunodominant Primary Sequence-Dependent B-Cell EpitopeStaphylococcus 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...
Research Article | Therapeutics and PreventionChlorpromazine and Amitriptyline Are Substrates and Inhibitors of the AcrB Multidrug Efflux PumpEfflux 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,...
Author Reply | Therapeutics and PreventionReply to Siniorakis et al., “COVID-19 Interference with Renin-Angiotensin System in the Context of Heart Failure”
Research Article | Therapeutics and PreventionAntiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in FerretsThe 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...