Tioconazole exerts anti-TB activity by destroying cell integrity

Area of Science:

• Microbiology
• Drug Discovery
• Infectious Diseases

Background:

• Drug-resistant tuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infection necessitate novel anti-TB agents.
• Conventional TB treatments are lengthy, toxic, and increasingly ineffective against resistant strains.

Purpose of the Study:

• To investigate the anti-tubercular activity and antibacterial mechanisms of tioconazole.
• To evaluate tioconazole as a potential novel therapeutic agent against Mycobacterium tuberculosis (Mtb).

Main Methods:

• Determined minimum inhibitory concentrations (MICs) of tioconazole against Mtb H37Ra and H37Rv.
• Assessed tioconazole's activity using Mtb H37Ra CYP121 conditional mutant and in the presence of pristinamycin.
• Examined morphological changes and intracellular ATP levels in Mtb cells treated with tioconazole.

Main Results:

• Tioconazole demonstrated significant antibacterial activity with MICs of 4 µg/mL (Mtb H37Ra) and 1 µg/mL (Mtb H37Rv).
• MIC against Mtb H37Ra decreased to 2 µg/mL when using cholesterol or palmitic acid as a solo carbon source.
• Tioconazole treatment induced cell surface invaginations/bulges and reduced intracellular ATP levels by ~50%, indicating disruption of cell integrity and lipid metabolism.

Conclusions:

• Tioconazole exhibits potent anti-tubercular activity against Mtb.
• The drug appears to exert its effects by compromising the cell wall and membrane integrity, likely through lipid metabolism inhibition.
• Tioconazole presents a promising candidate for developing new anti-TB drugs.