Therapeutics and Prevention
Research Article | Therapeutics and PreventionDissecting Colistin Resistance Mechanisms in Extensively Drug-Resistant Acinetobacter baumannii Clinical IsolatesThe discovery of antibiotics revolutionized modern medicine and enabled us to cure previously deadly bacterial infections. However, a progressive increase in antibiotic resistance rates is a major and global threat for our health care system. Colistin represents one of our last-resort antibiotics that is still active against most Gram-negative bacterial pathogens, but increasing resistance is reported worldwide, in particular due to the...
Editor's Pick Research Article | Therapeutics and PreventionAntifungal Activity of the Enterococcus faecalis Peptide EntV Requires Protease Cleavage and Disulfide Bond FormationEnterococcus faecalis and Candida albicans are among the most important and problematic pathobionts, organisms that normally are harmless commensals but can cause dangerous infections in immunocompromised hosts. In fact, both organisms are listed by the Centers for Disease Control and Prevention as...
Research Article | Therapeutics and PreventionResistance to the Tat Inhibitor Didehydro-Cortistatin A Is Mediated by Heightened Basal HIV-1 TranscriptionHIV-1 Tat enhances viral RNA transcription by binding to TAR and recruiting activating factors. Tat enhances its own transcription via a positive-feedback loop. Didehydro-cortistatin A (dCA) is a potent Tat inhibitor, reducing HIV-1 transcription and preventing viral rebound. dCA activity demonstrates the potential of the “block-and-lock” functional cure approaches. We investigated the viral genetic barrier to dCA resistance in...
Editor's Pick Research Article | Therapeutics and PreventionA Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B VaccineThere are two licensed meningococcal capsular B vaccines. Both contain recombinant factor H binding protein (FHbp), which can bind to host complement factor H (FH). The limitations of these vaccines include a lack of protection against some meningococcal strains and the potential to elicit autoantibodies to FH. We immunized infant macaques with a native outer membrane vesicle (NOMV) vaccine with genetically attenuated endotoxin and...
Editor's Pick Research Article | Therapeutics and PreventionThe Landscape of Phenotypic and Transcriptional Responses to Ciprofloxacin in Acinetobacter baumannii: Acquired Resistance Alleles Modulate Drug-Induced SOS Response and Prophage ReplicationFluoroquinolones have been extremely successful antibiotics due to their ability to target multiple bacterial enzymes critical to DNA replication, the topoisomerases DNA gyrase and topo IV. Unfortunately, mutations lowering drug affinity for both enzymes are now widespread, rendering these drugs ineffective for many pathogens. To undermine this form of resistance, we examined how bacteria with target alterations differentially cope with...
Research Article | Therapeutics and PreventionBlacklists and Whitelists To Tackle Predatory Publishing: a Cross-Sectional Comparison and Thematic AnalysisPredatory journals are spurious scientific outlets that charge fees for editorial and publishing services that they do not provide. Their lack of quality assurance of published articles increases the risk that unreliable research is published and thus jeopardizes the integrity and credibility of research as a whole. There is increasing awareness of the risks associated with predatory publishing, but efforts to address this situation are...
Research Article | Therapeutics and PreventionEfficacy of Oral Encochleated Amphotericin B in a Mouse Model of Cryptococcal MeningoencephalitisCryptococcus neoformans is a significant global fungal pathogen that kills an estimated quarter of a million HIV-infected individuals yearly and has poor outcomes despite therapy. The most effective therapy, amphotericin B, is highly effective in killing the fungus but is available only in highly toxic, intravenous formulations that are unavailable in most of the...
Editor's Pick Research Article | Therapeutics and PreventionMucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea PigsRecently, the protective effect of anti-neuraminidase immunity has been highlighted by several studies in humans and animal models. However, so far the role that anti-neuraminidase immunity plays in inhibition of virus transmission has not been explored. In addition, neuraminidase has been ignored as an antigen for influenza virus vaccines. We show here that neuraminidase-based vaccines can inhibit the transmission of influenza virus....
Research Article | Therapeutics and PreventionEarly Steps in Herpes Simplex Virus Infection Blocked by a Proteasome InhibitorViruses usurp host cell functions to advance their replicative agenda. HSV relies on cellular proteasome activity for successful infection. Proteasome inhibitors, such as MG132, block HSV infection at multiple stages of the infectious cycle. Targeting host cell processes for antiviral intervention is an unconventional approach that might limit antiviral resistance. Here we demonstrated that the proteasome inhibitor bortezomib, which is...
Research Article | Therapeutics and PreventionInfluenza “Trains” the Host for Enhanced Susceptibility to Secondary Bacterial InfectionEnhanced susceptibility to 2° bacterial infections following infection with influenza virus is a global health concern that accounts for many hospitalizations and deaths, particularly during pandemics. The complexity of the impaired host immune response during 2° bacterial infection has been widely studied. Both type I IFN and neutrophil dysfunction through decreased chemokine production have been implicated as mechanisms underlying...