Therapeutics and Prevention
Research Article | Therapeutics and PreventionThe Biofilm Inhibitor Carolacton Enters Gram-Negative Cells: Studies Using a TolC-Deficient Strain of Escherichia coliThe emergence of pathogens resistant against most or all of the antibiotics currently used in human therapy is a global threat, and therefore the search for antimicrobials with novel targets and modes of action is of utmost importance. The myxobacterial secondary metabolite carolacton had previously been shown to inhibit biofilm formation and growth of streptococci. Here, we investigated if carolacton could act against Gram-negative...
Research Article | Therapeutics and PreventionThe Potential Therapeutic Agent Mepacrine Protects Caco-2 Cells against Clostridium perfringens Enterotoxin ActionClostridium perfringens enterotoxin (CPE) causes the gastrointestinal (GI) symptoms of a common bacterial food poisoning and several nonfoodborne human GI diseases. A previous study showed that, via an undetermined mechanism, the presence of mepacrine blocks CPE-induced electrophysiologic activity in artificial membranes. The current study now demonstrates that...
Research Article | Therapeutics and PreventionGenetic Validation of Leishmania donovani Lysyl-tRNA Synthetase Shows that It Is Indispensable for Parasite Growth and InfectivityAminoacyl-tRNA synthetases are housekeeping enzymes essential for protein translation, providing charged tRNAs for the proper construction of peptide chains. These enzymes provide raw materials for protein translation and also ensure fidelity of translation. L. donovani is a protozoan parasite that causes visceral leishmaniasis. It is a continuously proliferating parasite that depends heavily on efficient protein translation....
Research Article | Therapeutics and PreventionAn Aptamer-Based Biosensor for the Azole Class of Antifungal DrugsWe have developed the first aptamer directed toward the azole class of antifungal drugs and a functional biosensor for these drugs. This aptamer has a unique secondary structure that allows it to bind to highly hydrophobic drugs. The aptamer works as a capture component of a graphene field effect transistor device. These devices can provide a quick and easy assay for determining drug concentrations. These will be useful for therapeutic...
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...