Department of Biology and Biotechnology 'Lazzaro Spallanzani', University of Pavia, Pavia, Italy.
Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia.
Int J Antimicrob Agents. 2024 Oct;64(4):107278. doi: 10.1016/j.ijantimicag.2024.107278. Epub 2024 Jul 26.
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.
在患有囊性纤维化和慢性阻塞性肺疾病的人群中，肺部感染的发病率在全球范围内正在上升。脓肿分枝杆菌与这些人群的慢性肺部恶化有关。脓肿分枝杆菌对大多数常规抗生素的固有耐药性危及了治疗成功率。迄今为止，尚无专门针对脓肿分枝杆菌的单一药物被开发出来。本研究的目的是将 VOMG 鉴定为一种针对脓肿分枝杆菌和其他病原体的新型活性吡啶酮核心类药物。
采用包括微生物学、化学、生物化学和转录组学程序在内的多学科方法来验证 VOMG 作为有前途的抗脓肿分枝杆菌药物候选物的作用。
据作者所知，这是第一项报道 VOMG 对脓肿分枝杆菌和其他病原体具有体外和体内杀菌活性的研究。该化合物不仅对脓肿分枝杆菌生物膜具有活性，而且还具有良好的药理学（ADME-Tox）特性。耐药性研究的频率未能分离出耐药突变体。VOMG 抑制细胞分裂，特别是 FtsZ 酶。
VOMG 是一种针对脓肿分枝杆菌的新型类药分子，通过抑制细胞分裂对其他微生物病原体具有广谱活性。
