Photoinactivation of dormant Mycobacterium smegmatis due to its endogenous porphyrins.

Autor: Shleeva MO; A.N. Bach Institute of Biochemistry, Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia. margoshleeva@gmail.com., Savitsky AP; A.N. Bach Institute of Biochemistry, Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia., Nikitushkin VD; A.N. Bach Institute of Biochemistry, Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia., Solovyev ID; A.N. Bach Institute of Biochemistry, Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia., Kazachkina NI; A.N. Bach Institute of Biochemistry, Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia., Perevarov VV; A.N. Bach Institute of Biochemistry, Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia., Kaprelyants AS; A.N. Bach Institute of Biochemistry, Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia.
Jazyk: angličtina
Zdroj: Applied microbiology and biotechnology [Appl Microbiol Biotechnol] 2019 Dec; Vol. 103 (23-24), pp. 9687-9695. Date of Electronic Publication: 2019 Nov 12.
DOI: 10.1007/s00253-019-10197-3
Abstrakt: Mycobacterium tuberculosis is able to transition into a dormant state, causing a latent state of tuberculosis. Dormant mycobacteria acquire phenotypic resistance to all known antibacterial drugs; they are also able to maintain vitality in the host for decades and become active, causing the active form of the disease. In order to cure latent tuberculosis, new approaches should be developed. Earlier, we discovered accumulation in significant concentrations of porphyrins in dormant Mycobacterium smegmatis, which is a close, fast-growing relative of the causative agent of tuberculosis. In this study, we explore a new possibility to kill dormant mycobacteria by photodynamic inactivation (PDI) using accumulated porphyrins as endogenous photosensitisers. The dormant M. smegmatis were obtained under gradual acidification in Sauton's medium, for 14 days. Cells were exposed to light with different wavelengths emitted by three Spectra X light-emitting diodes (395/25, 470/24, 575/25 nm) and one separated 634-nm LED for 15 min. An increase in the concentration of coproporphyrin in M. smegmatis after 6 days of growth correlated with the beginning of a decrease in metabolic activity and formation of ovoid dormant forms. Dormant bacteria were sensitive to PDI and killed after 15-30 min of illumination, in contrast to active cells. The greatest inactivation of dormant mycobacteria occurred at 395 and 575 nm, which coincides with the main maximum of the absorption spectrum of extracted porphyrins. We, for the first time, demonstrate a successful application of PDI for inactivation of dormant mycobacteria, due to significant accumulation of endogenous photosensitisers-porphyrins.
Databáze: MEDLINE
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