Therapeutics and Prevention
Editor's Pick Research Article | Therapeutics and PreventionStructural Characterization of Acidic M17 Leucine Aminopeptidases from the TriTryps and Evaluation of Their Role in Nutrient Starvation in Trypanosoma bruceiLeucine aminopeptidases (LAPs) catalyze the hydrolysis of the N-terminal amino acid of peptides and are considered potential drug targets. They are involved in multiple functions ranging from host cell invasion and provision of essential amino acids to site-specific homologous recombination and transcription regulation. In kinetoplastid parasites, there are at least three distinct LAPs. The availability of the crystal structures...
Research Article | Therapeutics and PreventionAdaptive Mistranslation Accelerates the Evolution of Fluconazole Resistance and Induces Major Genomic and Gene Expression Alterations in Candida albicansInfectious diseases caused by drug-resistant fungi are an increasing threat to public health because of the high mortality rates and high costs associated with treatment. Thus, understanding of the molecular mechanisms of drug resistance is of crucial interest for the medical community. Here we investigated the role of regulated protein mistranslation, a characteristic mechanism used by...
Research Article | Therapeutics and PreventionnBioChip, a Lab-on-a-Chip Platform of Mono- and Polymicrobial Biofilms for High-Throughput Downstream ApplicationsWith an estimated 80% of infections being associated with a biofilm mode of growth and the ensuing recalcitrance of these biofilms with respect to conventional antibiotic treatment leading to high mortality rates, there is a dire and unmet need for the development of novel approaches to prevent, treat, and control these infections. Both bacteria and fungi are capable of forming biofilms that are inherently fragile and often...
Research Article | Therapeutics and PreventionImplementation of Isavuconazole in a Fluorescence-Based High-Performance Liquid Chromatography Kit Allowing Simultaneous Detection of All Four Currently Licensed Mold-Active TriazolesIsavuconazole is a new broad-spectrum triazole agent recently approved for the treatment of both invasive aspergillosis and mucormycosis. Currently, there is no consensus regarding the potential need for TDM of isavuconazole, and no therapeutic window has been defined. However, at the ECIL-6 meeting in 2015, it was advised that TDM is indicated in a number of different settings. In this study, we describe a rapid and validated isocratic...
Research Article | Therapeutics and PreventionDiscovery of a Novel Antifungal Agent in the Pathogen BoxCryptococcus neoformans and Candida albicans are two major human fungal pathogens and together account for over 1.4 million infections annually, with very high mortality rates. These fungi often infect immunocompromised individuals, such as HIV/AIDS patients. In an effort to identify novel drugs...
Observation | Therapeutics and PreventionA Novel Staphylococcus Podophage Encodes a Unique Lysin with Unusual Modular DesignThe spread of antibiotic resistance among bacterial pathogens is inciting a global public health crisis. Drug-resistant Staphylococcus species, especially S. aureus and S. epidermidis, have emerged in both hospital and community settings, underscoring the urgent need for new strategies to...
Research Article | Therapeutics and PreventionFluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia PathogensRising resistance rates for macrolides, fluoroquinolones, and β-lactams in the most common pathogens associated with community-acquired bacterial pneumonia (CABP) are of concern, especially for cases of moderate to severe infections in vulnerable populations such as the very young and the elderly. New antibiotics that are active against multidrug-resistant Streptococcus pneumoniae and Staphylococcus aureus are needed...
Research Article | Therapeutics and PreventionTgPRELID, a Mitochondrial Protein Linked to Multidrug Resistance in the Parasite Toxoplasma gondiiWe report the discovery of TgPRELID, a previously uncharacterized mitochondrial protein linked to multidrug resistance in the parasite Toxoplasma gondii. Drug resistance remains a major problem in the battle against parasitic infection, and understanding how TgPRELID mutations augment resistance to multiple, distinct compounds will reveal needed insights into the...
Research Article | Therapeutics and PreventionA Novel Protective Vaccine Antigen from the Core Escherichia coli GenomeE. coli is a multifaceted pathogen of major significance to global human health and an important contributor to increasing antibiotic resistance. Given the paucity of therapies still effective against multidrug-resistant pathogenic E. coli strains, novel treatment and prevention strategies are...
Research Article | Therapeutics and PreventionDe Novo Pyrimidine Biosynthesis Connects Cell Integrity to Amphotericin B Susceptibility in Cryptococcus neoformansSynergy between AmB and nucleotide biosynthetic pathways has been documented, but the mechanism of this interaction has not been delineated. Results from this study suggest a correlation between uridine nucleotide biosynthesis and cell integrity likely mediated through the pool of nucleotide-sugar conjugates, which are precursor molecules for both capsule and cell wall of C...