Spermine enhances the activity of anti-tuberculosis drugs

Microbiol Spectr. 2024 Jan 11;12(1):e0356823. doi: 10.1128/spectrum.03568-23. Epub 2023 Dec 14.

Abstract

This is the first study that attempted to demonstrate the mechanisms of reactive oxygen species (ROS) generation by spermine (Spm) in Mycobacterium tuberculosis (M.tb). Furthermore, this is the first study to demonstrate that it is able to enhance the activity of currently available and World Health Organization (WHO)-approved tuberculosis (TB) drugs. Spermine can easily be obtained since it is already found in our diet. Moreover, as opposed to conventional antibiotics, it is less toxic to humans since it is found in millimolar concentrations in the body. Finally, with the difficulty of curing TB with conventional antibiotics, this study suggests that less toxic molecules, such as Spm, could in a long-term perspective be incorporated in a TB regimen to boost the treatment.

Keywords: Mycobacterium tuberculosis (M.tb); bedaquiline (BDQ); cumene hydroperoxide (CuOOH); isoniazid (INH); para-aminosalicylic acid (PAS); reactive oxygen species (ROS); rifampicin (RIF); spermine (Spm); tuberculosis (TB).

MeSH terms

  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Humans
  • Isoniazid
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis*
  • Rifampin / therapeutic use
  • Spermine / pharmacology
  • Spermine / therapeutic use
  • Tuberculosis* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / microbiology

Substances

  • Antitubercular Agents
  • Spermine
  • Isoniazid
  • Rifampin