mouse model
Experimental TherapeuticsTherapeutic Potential of Coumestan Pks13 Inhibitors for TuberculosisPolyketide synthase 13 (Pks13) is an important enzyme found in Mycobacterium tuberculosis that condenses two fatty acyl chains to produce α-alkyl β-ketoesters, which in turn serve as the precursors for the synthesis of mycolic acids that are essential building blocks for maintaining the cell wall integrity of...
Experimental TherapeuticsActivity of Clofazimine and TBI-166 against Mycobacterium tuberculosis in Different Administration Intervals in Mouse Tuberculosis ModelsClofazimine (CLO) and TBI-166 belong to the riminophenazine class of antimicrobial agent. TBI-166 exhibited promising antituberculosis activity in vitro and in animal models and is currently under phase I clinical development for the treatment of tuberculosis in China.
Antiviral AgentsBroad-Spectrum Antiviral Activity of 3′-Deoxy-3′-Fluoroadenosine against Emerging FlavivirusesEmerging flaviviruses are causative agents of severe and life-threatening diseases, against which no approved therapies are available. Among the nucleoside analogues, which represent a promising group of potentially therapeutic compounds, fluorine-substituted nucleosides are characterized by unique structural and functional properties.
Editor's Pick Mechanisms of ResistanceMutations in fbiD (Rv2983) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosisThe nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior in vitro studies suggest a relatively low barrier to nitroimidazole resistance in Mycobacterium tuberculosis, but clinical evidence is limited to date. We selected pretomanid-resistant...
Antiviral AgentsMonoclonal Antibody Therapy Protects Pharmacologically Immunosuppressed Mice from Lethal Infection with Influenza B VirusHuman influenza A and B viruses are highly contagious and cause similar illnesses and seasonal epidemics. Currently available antiviral drugs have limited efficacy in humans with compromised immune systems; therefore, alternative strategies for protection are needed. Here, we investigated whether monoclonal antibodies (MAbs) targeting hemagglutinin (HA) and/or neuraminidase (NA) proteins would protect immunosuppressed mice from severe...
SusceptibilityAR-12 Exhibits Direct and Host-Targeted Antibacterial Activity toward Mycobacterium abscessusTherapeutic options for Mycobacterium abscessus infections are extremely limited. New or repurposed drugs are needed. The anti-M. abscessus activity of AR-12 (OSU-03012), reported to express broad-spectrum antimicrobial effects, was investigated in vitro and in vivo. Antimicrobial...
Experimental TherapeuticsSynergistic Activity of Clofazimine and Clarithromycin in an Aerosol Mouse Model of Mycobacterium avium InfectionInfections with nontuberculous mycobacteria (NTM) have a poor prognosis in patients with underlying respiratory diseases. Clofazimine (CFZ) showed both experimental and clinical promising results against clinically relevant NTM. However, there are no data on CFZ in combination with the current recommended treatment; therefore, we aimed to study its in vivo activity in an aerosol mouse model of...
Experimental TherapeuticsIdentification of Antibiotics That Diminish Disease in a Murine Model of Enterohemorrhagic Escherichia coli InfectionInfections with enterohemorrhagic Escherichia coli (EHEC) cause disease ranging from mild diarrhea to hemolytic-uremic syndrome (HUS) and are the most common cause of renal failure in children in high-income countries. The severity of the disease derives from the release of Shiga toxins (Stx). The use of antibiotics to treat EHEC infections is generally avoided, as it...
Editor's Pick Experimental TherapeuticsMechanistic Modeling of Mycobacterium tuberculosis Infection in Murine Models for Drug and Vaccine Efficacy StudiesTuberculosis (TB) drug, regimen, and vaccine development rely heavily on preclinical animal experiments, and quantification of bacterial and immune response dynamics is essential for understanding drug and vaccine efficacy. A mechanism-based model was built to describe Mycobacterium tuberculosis H37Rv infection over time in BALB/c and athymic nude mice, which...
Editor's Pick Experimental TherapeuticsRifabutin Is Active against Mycobacterium abscessus in MiceThere is no reliable cure for Mycobacterium abscessus lung disease. Rifampin is not used clinically due to poor in vitro potency. In contrast, we have shown that rifabutin, another approved rifamycin used to treat tuberculosis, is potent in vitro against M. abscessus. Here, we...