Mycobacterium
Mechanisms of Action: Physiological EffectsLack of Specificity of Phenotypic Screens for Inhibitors of the Mycobacterium tuberculosis FAS-II SystemPhenotypic screening of inhibitors of the essential Mycobacterium tuberculosis FAS-II dehydratase HadAB led to the identification of GSK3011724A, a compound previously reported to inhibit the condensation step of FAS-II. Whole-cell-based and cell-free assays confirmed the lack of activity of GSK3011724A against the dehydratase despite evidence of cross-resistance...
Mechanisms of Action: Physiological EffectsThe Unique C-Terminal Extension of Mycobacterial F-ATP Synthase Subunit α Is the Major Contributor to Its Latent ATP Hydrolysis ActivityMycobacterial F1Fo-ATP synthases (α3:β3:γ:δ:ε:a:b:b′:c9) are incapable of ATP-driven proton translocation due to their latent ATPase activity. This prevents wasting of ATP and altering of the proton motive force, whose dissipation is lethal to mycobacteria. We demonstrate that the mycobacterial C-terminal extension of nucleotide-binding subunit α...
Mechanisms of Action: Physiological EffectsAdduct Formation of Delamanid with NAD in MycobacteriaDelamanid (DLM), a nitro-dihydroimidazooxazole derivative currently approved for pulmonary multidrug-resistant tuberculosis (TB) therapy, is a prodrug activated by mycobacterial 7,8-didemethyl-8-hydroxy 5-deazaflavin electron transfer coenzyme (F420)-dependent nitroreductase (Ddn). Despite inhibiting the biosynthesis of a subclass of mycolic acids, the active DLM metabolite remained unknown. Comparative liquid chromatography-...
Editor's Pick Challenging Clinical Case in Antimicrobial ResistanceSuccessful Systemic and Topical Treatment of Mycobacterium abscessus OtomastoiditisMycobacterium abscessus is an extensively drug-resistant opportunistic pathogen that can cause chronic otomastoiditis. There are no evidence-based treatment regimens for this severe infection. We treated four children with M. abscessus otomastoiditis with a structured regimen of topical imipenem and...
Mechanisms of Action: Physiological EffectsWatching DNA Replication Inhibitors in Action: Exploiting Time-Lapse Microfluidic Microscopy as a Tool for Target-Drug Interaction Studies in MycobacteriumSpreading resistance to antibiotics and the emergence of multidrug-resistant strains have become frequent in many bacterial species, including mycobacteria, which are the causative agents of severe diseases and which have profound impacts on global health.
Biologic Response ModifiersMycobacterium abscessus Cells Have Altered Antibiotic Tolerance and Surface Glycolipids in Artificial Cystic Fibrosis Sputum MediumMycobacterium abscessus is a biofilm-forming, multidrug-resistant nontuberculous mycobacterial (NTM) pathogen increasingly found in cystic fibrosis patients. Antibiotic treatment for these infections is often unsuccessful, partly due to M. abscessus’s high intrinsic antibiotic resistance.
...
Chemistry; BiosynthesisIndole-2-Carboxamides Are Active against Mycobacterium abscessus in a Mouse Model of Acute InfectionNontuberculous mycobacteria (NTM) pathogens particularly infect patients with structural lung disorders. We previously reported novel indole-2-carboxamides (ICs) that are active against a wide panel of NTM pathogens.
- Mechanisms of ResistanceImidazopyridine Compounds Inhibit Mycobacterial Growth by Depleting ATP Levels