Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrins
Abstract 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. tu...
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| Format: | Article |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-51227-z |
| _version_ | 1827327491532914688 |
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| author | Margarita O. Shleeva Irina A. Linge Ivan A. Gligonov Galina N. Vostroknutova Denis M. Shashin Andrey M. Tsedilin Alexander S. Apt Arseny S. Kaprelyants Alexander P. Savitsky |
| author_facet | Margarita O. Shleeva Irina A. Linge Ivan A. Gligonov Galina N. Vostroknutova Denis M. Shashin Andrey M. Tsedilin Alexander S. Apt Arseny S. Kaprelyants Alexander P. Savitsky |
| author_sort | Margarita O. Shleeva |
| collection | DOAJ |
| description | Abstract 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/cm2) 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. |
| first_indexed | 2024-03-07T15:02:01Z |
| format | Article |
| id | doaj.art-0e905edfdb7b4f9784a8b789e6ede5a3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:02:01Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0e905edfdb7b4f9784a8b789e6ede5a32024-03-05T19:05:19ZengNature PortfolioScientific Reports2045-23222024-01-0114111710.1038/s41598-024-51227-zAcquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrinsMargarita O. Shleeva0Irina A. Linge1Ivan A. Gligonov2Galina N. Vostroknutova3Denis M. Shashin4Andrey M. Tsedilin5Alexander S. Apt6Arseny S. Kaprelyants7Alexander P. Savitsky8A.N. Bach Institute of Biochemistry, Federal Research Centre ‘Fundamentals of Biotechnology’ of the Russian Academy of SciencesLaboratory for Immunogenetics, Central Tuberculosis Research InstituteA.N. Bach Institute of Biochemistry, Federal Research Centre ‘Fundamentals of Biotechnology’ of the Russian Academy of SciencesA.N. Bach Institute of Biochemistry, Federal Research Centre ‘Fundamentals of Biotechnology’ of the Russian Academy of SciencesA.N. Bach Institute of Biochemistry, Federal Research Centre ‘Fundamentals of Biotechnology’ of the Russian Academy of SciencesA.N. Bach Institute of Biochemistry, Federal Research Centre ‘Fundamentals of Biotechnology’ of the Russian Academy of SciencesLaboratory for Immunogenetics, Central Tuberculosis Research InstituteA.N. Bach Institute of Biochemistry, Federal Research Centre ‘Fundamentals of Biotechnology’ of the Russian Academy of SciencesA.N. Bach Institute of Biochemistry, Federal Research Centre ‘Fundamentals of Biotechnology’ of the Russian Academy of SciencesAbstract 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/cm2) 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.https://doi.org/10.1038/s41598-024-51227-z |
| spellingShingle | Margarita O. Shleeva Irina A. Linge Ivan A. Gligonov Galina N. Vostroknutova Denis M. Shashin Andrey M. Tsedilin Alexander S. Apt Arseny S. Kaprelyants Alexander P. Savitsky Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrins Scientific Reports |
| title | Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrins |
| title_full | Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrins |
| title_fullStr | Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrins |
| title_full_unstemmed | Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrins |
| title_short | Acquiring of photosensitivity by Mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous Zn–porphyrins |
| title_sort | acquiring of photosensitivity by mycobacterium tuberculosis in vitro and inside infected macrophages is associated with accumulation of endogenous zn porphyrins |
| url | https://doi.org/10.1038/s41598-024-51227-z |
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