Photoinactivation of Mycobacterium tuberculosis and Mycobacterium smegmatis by Near-Infrared Radiation Using a Trehalose-Conjugated Heptamethine Cyanine

• Published in: International journal of molecular sciences 2024-08, Vol.25 (15), p.8505
• Main Authors: Kozobkova, Nataliya V, Samtsov, Michael P, Lugovski, Anatol P, Bel'ko, Nikita V, Tarasov, Dmitri S, Kaprelyants, Arseny S, Savitsky, Alexander P, Shleeva, Margarita O
• Format: Article
• Language: English
• Subjects: antibacterial photodynamic inactivation; Antibiotics; Antitubercular agents; Bacteria; Bacterial infections; BCG; BCG vaccines; Carbocyanines - chemistry; Carbocyanines - pharmacology; Chemotherapy; Detergents; Disease; dormant mycobacteria; Drug resistance; Drug resistance in microorganisms; Dyes; Infections; Infrared Rays; Light; Methylene blue; mycobacteria; Mycobacterium smegmatis - drug effects; Mycobacterium smegmatis - radiation effects; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - radiation effects; Pathogens; Photochemotherapy - methods; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Radiation; Skin; trehalose; Trehalose - chemistry; Trehalose - pharmacology; tricarbocyanine dye; Tuberculosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25158505

The spread of multidrug-resistant mycobacterium strains requires the development of new approaches to combat diseases caused by these pathogens. For that, photodynamic inactivation (PDI) is a promising approach. In this study, a tricarbocyanine (TCC) is used for the first time as a near-infrared (740 nm) activatable PDI photosensitizer to kill mycobacteria with deep light penetration. For better targeting, a novel tricarbocyanine dye functionalized with two trehalose units (TCC2Tre) is developed. The photodynamic effect of the conjugates against mycobacteria, including , is evaluated. Under irradiation, TCC2Tre causes more effective killing of mycobacteria compared to the photosensitizer without trehalose conjugation, with 99.99% dead vegetative cells of and . In addition, effective photoinactivation of dormant forms of is observed after incubation with TCC2Tre. Mycobacteria treated with TCC2Tre are more sensitive to 740 nm light than the Gram-positive and the Gram-negative . For the first time, this study demonstrates the proof of principle of in vitro PDI of mycobacteria including the fast-growing and the slow-growing using near-infrared activatable photosensitizers conjugated with trehalose. These findings are useful for the development of new efficient alternatives to antibiotic therapy.