The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division

• Published in: International journal of antimicrobial agents 2024-10, Vol.64 (4), p.107278, Article 107278
• Main Authors: Degiacomi, Giulia, Chiarelli, Laurent R., Riabova, Olga, Loré, Nicola Ivan, Muñoz-Muñoz, Lara, Recchia, Deborah, Stelitano, Giovanni, Postiglione, Umberto, Saliu, Fabio, Griego, Anna, Scoffone, Viola Camilla, Kazakova, Elena, Scarpa, Edoardo, Ezquerra-Aznárez, José Manuel, Stamilla, Alessandro, Buroni, Silvia, Tortoli, Enrico, Rizzello, Loris, Sassera, Davide, Ramón-García, Santiago, Cirillo, Daniela Maria, Makarov, Vadim, Pasca, Maria Rosalia
• Format: Article
• Language: English
• Subjects: Cell division; FtsZ; Mycobacterium abscessus; Non-tuberculous mycobacterium
• ISSN: 0924-8579; 1872-7913; 1872-7913
• DOI: 10.1016/j.ijantimicag.2024.107278

•VOMG is a drug-like molecule active against Mycobacterium abscessus.•VOMG also has broad-spectrum activity against other microbial pathogens.•VOMG has a new mode of action inhibiting cell division, particularly FtsZ activity.•VOMG is active against M. abscessus in vitro, in vivo and against biofilm.•VOMG is a water-soluble anti-M. abscessus compound with good ADME/Tox properties. 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. A multi-disciplinary approach including microbiological, chemical, biochemical and transcriptomics procedures was used to validate VOMG as a promising anti-M. abscessus drug candidate. 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. VOMG is a new drug-like molecule active against M. abscessus, inhibiting cell division with broad-spectrum activity against other microbial pathogens. [Display omitted]