Therapeutics and Prevention
Research Article | Therapeutics and PreventionIntravaginal Administration of Interleukin 12 during Genital Gonococcal Infection in Mice Induces Immunity to Heterologous Strains of Neisseria gonorrhoeaeGenital infection with Neisseria gonorrhoeae (gonorrhea) is a significant cause of reproductive tract morbidity in women, leading to pelvic inflammatory disease, tubal factor infertility, and increased risk for ectopic pregnancy. WHO estimates that 78 million new infections occur annually worldwide. In the United States, >350,000 cases are reported annually, but...
Research Article | Therapeutics and PreventionAn Optimized Synthetic-Bioinformatic Natural Product Antibiotic Sterilizes Multidrug-Resistant Acinetobacter baumannii-Infected WoundsNatural product-inspired antibiotics have saved millions of lives and played a critical role in modern medicine. However, the emergence of drug-resistant pathogens is outpacing the rate at which new clinically useful antibiotics are being discovered. The lack of a means to combat infections caused by multidrug-resistant (MDR) Acinetobacter baumannii is of particular...
Research Article | Therapeutics and PreventionTargeted Phenotypic Screening in Plasmodium falciparum and Toxoplasma gondii Reveals Novel Modes of Action of Medicines for Malaria Venture Malaria Box MoleculesThe phylum Apicomplexa includes many human and animal pathogens, such as Plasmodium falciparum (human malaria) and Toxoplasma gondii (human and animal toxoplasmosis). Widespread resistance to current antimalarials and the lack of a commercial vaccine necessitate novel pharmacological...
Minireview | Therapeutics and PreventionTargeting Virulence in Staphylococcus aureus by Chemical Inhibition of the Accessory Gene Regulator System In VivoMethicillin-resistant Staphylococcus aureus (MRSA) presents one of the most serious health concerns worldwide. The WHO labeled it as a “high-priority” pathogen in 2017, also citing the more recently emerged vancomycin-intermediate and -resistant strains.
Research Article | Therapeutics and PreventionRecombinant Zika Virus Subunits Are Immunogenic and Efficacious in MiceThe recent outbreaks of Zika virus (ZIKV) infection in French Polynesia, the Caribbean, and the Americas have highlighted the severe neuropathological sequelae that such an infection may cause. The development of a safe, effective ZIKV vaccine is critical for several reasons: (i) the difficulty in diagnosing an active infection due to common nonspecific symptoms, (ii) the lack of a specific antiviral therapy, and (iii) the potentially...
Research Article | Therapeutics and PreventionMaternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant MacaquesWithout novel strategies to prevent mother-to-child HIV-1 transmission, more than 5% of HIV-1-exposed infants will continue to acquire HIV-1, most through breastfeeding. This study of rhesus macaque dam-and-infant pairs is the first preclinical study to investigate the protective role of transplacentally transferred HIV-1 vaccine-elicited antibodies and HIV-1 vaccine-elicited breast milk antibody responses in infant oral virus...
Research Article | Therapeutics and PreventionA Single Amino Acid Change in the Marburg Virus Glycoprotein Arises during Serial Cell Culture Passages and Attenuates the Virus in a Macaque Model of DiseaseMarburg virus (MARV) causes disease with a high case fatality rate, and there are no approved vaccines or therapies. Serial amplification of viruses in cell culture often results in accumulation of mutations, but the effect of such cell culture passage on MARV is unclear. Serial passages of MARV resulted in a single mutation in the region encoding the glycoprotein (GP). This is a region where mutations can have important consequences on...
Editor's Pick Research Article | Therapeutics and PreventionVaccination with a Recombinant H7 Hemagglutinin-Based Influenza Virus Vaccine Induces Broadly Reactive Antibodies in HumansZoonotic infections with high case fatality rates caused by avian H7N9 influenza viruses have been reported since early 2013 in China. Since then, the fifth wave of the H7N9 epidemic emerged in China, resulting in higher numbers of laboratory-confirmed cases than in previous years. Recently, H7N9 has started to antigenically drift and split into two new lineages, the Pearl River Delta and Yangtze River Delta clades, which do not match...
Research Article | Therapeutics and PreventionCharacterization of the Mechanisms of Daptomycin Resistance among Gram-Positive Bacterial Pathogens by Multidimensional LipidomicsThis work comprehensively characterizes lipidomic changes underlying daptomycin resistance in three Gram-positive bacterial species, E. faecalis, S. aureus, and C. striatum, by using a novel three-dimensional lipidomics methodology based on advanced mass spectrometry. We demonstrated a...
Research Article | Therapeutics and PreventionInteraction of Antibiotics with Innate Host Defense Factors against Salmonella enterica Serotype NewportIt is becoming increasingly understood that the current paradigms of in vitro antimicrobial susceptibility testing may have significant shortcomings in predicting activity in vivo. This study evaluated the activity of several antibiotics alone and in combination against clinical isolates of Salmonella enterica serotype Newport (meningitis case)...