Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrins

Mycobacterium tuberculosis ( Mtb ) is able to transition into a dormant state, causing the latent state of tuberculosis. Dormant mycobacteria acquire resistance to all known antibacterial drugs and can survive in the human body for decades before becoming active. In the dormant forms of M. tuberculo...

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Published in:Scientific reports 2024-01, Vol.14 (1), p.846-846, Article 846
Main Authors: Shleeva, Margarita O., Linge, Irina A., Gligonov, Ivan A., Vostroknutova, Galina N., Shashin, Denis M., Tsedilin, Andrey M., Apt, Alexander S., Kaprelyants, Arseny S., Savitsky, Alexander P.
Format: Article
Language:English
Subjects:
631/326/421
631/45/56
631/57/2267
631/92/56
692/699/255/1856
Accumulation
Aminolevulinic acid
Aminolevulinic Acid - pharmacology
Humanities and Social Sciences
Humans
Macrophages
multidisciplinary
Multidrug resistance
Mycobacterium tuberculosis
Photosensitivity
Porphyrins
Science
Science (multidisciplinary)
Tetrapyrroles
Transcription activation
Transcriptomes
Tuberculosis
Zinc
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Summary:Mycobacterium tuberculosis ( Mtb ) is able to transition into a dormant state, causing the latent state of tuberculosis. Dormant mycobacteria acquire resistance to all known antibacterial drugs and can survive in the human body for decades before becoming active. In the dormant forms of M. tuberculosis, the synthesis of porphyrins and its Zn-complexes significantly increased when 5-aminolevulinic acid (ALA) was added to the growth medium. Transcriptome analysis revealed an activation of 8 genes involved in the metabolism of tetrapyrroles during the Mtb transition into a dormant state, which may lead to the observed accumulation of free porphyrins. Dormant Mtb viability was reduced by more than 99.99% under illumination for 30 min (300 J/cm 2 ) with 565 nm light that correspond for Zn–porphyrin and coproporphyrin absorptions. We did not observe any PDI effect in vitro using active bacteria grown without ALA. However, after accumulation of active cells in lung macrophages and their persistence within macrophages for several days in the presence of ALA, a significant sensitivity of active Mtb cells (ca. 99.99%) to light exposure was developed. These findings create a perspective for the treatment of latent and multidrug-resistant tuberculosis by the eradication of the pathogen in order to prevent recurrence of this disease.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-51227-z