1. The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division.
- Author
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Degiacomi G, Chiarelli LR, Riabova O, Loré NI, Muñoz-Muñoz L, Recchia D, Stelitano G, Postiglione U, Saliu F, Griego A, Scoffone VC, Kazakova E, Scarpa E, Ezquerra-Aznárez JM, Stamilla A, Buroni S, Tortoli E, Rizzello L, Sassera D, Ramón-García S, Cirillo DM, Makarov V, and Pasca MR
- Subjects
- Cell Division drug effects, Animals, Bacterial Proteins genetics, Humans, Cytoskeletal Proteins genetics, Cytoskeletal Proteins metabolism, Pyridines pharmacology, Mice, Mycobacterium abscessus drug effects, Anti-Bacterial Agents pharmacology, Microbial Sensitivity Tests, Mycobacterium Infections, Nontuberculous drug therapy, Mycobacterium Infections, Nontuberculous microbiology, Biofilms drug effects
- Abstract
Aims: The incidence of lung infections is increasing worldwide in individuals suffering from cystic fibrosis and chronic obstructive pulmonary disease. Mycobacterium abscessus is associated with chronic lung deterioration in these populations. The intrinsic resistance of M. abscessus to most conventional antibiotics jeopardizes treatment success rates. To date, no single drug has been developed targeting M. abscessus specifically. The objective of this study was to characterize VOMG, a pyrithione-core drug-like small molecule, as a new compound active against M. abscessus and other pathogens., Methods: A multi-disciplinary approach including microbiological, chemical, biochemical and transcriptomics procedures was used to validate VOMG as a promising anti-M. abscessus drug candidate., Results: To the authors' knowledge, this is the first study to report the in-vitro and in-vivo bactericidal activity of VOMG against M. abscessus and other pathogens. Besides being active against M. abscessus biofilm, the compound showed a favourable pharmacological (ADME-Tox) profile. Frequency of resistance studies were unable to isolate resistant mutants. VOMG inhibits cell division, particularly the FtsZ enzyme., Conclusions: VOMG is a new drug-like molecule active against M. abscessus, inhibiting cell division with broad-spectrum activity against other microbial pathogens., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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