The main pigment of the dormant<i>Mycobacterium smegmatis</i>is porphyrin

Nikitushkin, Vadim D.; Shleeva, Margarita O.; Zinin, Alexander I.; Трутнева, К. А.; Ostrovsky, D. N.; Kaprelyants, Arseny S.

doi:10.1093/femsle/fnw206

Cited by 29 publications

(29 citation statements)

References 17 publications

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“…Similarly, the finding of enzymes responsible for porphyrin synthesis (“unique”; Supplementary Table S2 ) in dormant cells is in line with the previously found substantial accumulation of copro- and uroporphyrins in dormant Msm cells ( Nikitushkin et al, 2016 ). Observations indicate that the antioxidant activities of porphyrins act to protect bacteria ( Patel and Day, 1999 ), animal tissues ( Antonova et al, 2010 ), and animal mitochondria ( Castello et al, 2008 ) against reactive oxygen species and toxic nucleophiles ( Fuhrhop, 1974 ).…”

Section: Discussionsupporting

confidence: 88%

Protein Composition of Mycobacterium smegmatis Differs Significantly Between Active Cells and Dormant Cells With Ovoid Morphology

et al. 2018

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Mycobacteria are able to form dormant cells, which survive for a long time without multiplication. The molecular mechanisms behind prolonged survival of dormant cells are not fully described. In particular, little information is known on biochemical processes which might take place in cells under dormancy. To gain insight into this problem, Mycobacterium smegmatis cells in deep dormant state were obtained after gradual acidification of the growth medium in prolonged stationary phase followed by 1 month of storage at room temperature. Such cells were characterized by low metabolic activity, including respiration, resistance to antibiotics, and altered morphology. The protein composition of cytoplasm and membrane fractions obtained from active and dormant cells were compared by 2D electrophoresis. Almost half of the proteins found in the proteome of dormant cells were absent in that of active cells. This result differs significantly from published results obtained in other studies employing different models of mycobacterium dormancy. This discrepancy could be explained by a deeper dormancy developed in the present model. A feature of a “dormant proteome” is high representation of enzymes involved in glycolysis and defense systems that inactivate or detoxify reactive oxygen and nitrogen species, aldehydes, and oxidized lipids. Dormant mycobacteria are enriched by degradative enzymes, which could eliminate damaged molecules, or the products of such degradation could be reutilized by the cell during prolonged storage. We suggest that some enzymes in dormant cells are inactive, having been used upon transition to the dormant state, or proteins stored in dormant cells for further cell reactivation. At the same time, some proteins could be functional and play roles in maintenance of cell metabolism, albeit at a very slow rate. This study provides a clue as to which biochemical processes could be active under dormancy to ensure long-term viability of dormant mycobacteria.

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Section: Discussionsupporting

confidence: 88%

Protein Composition of Mycobacterium smegmatis Differs Significantly Between Active Cells and Dormant Cells With Ovoid Morphology

et al. 2018

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“…Only one attempt to apply PDI in the treatment of dormant mycobacteria has been performed; dormant M. smegmatis formed in vitro after gradual acidification of the growth medium (Kudykina et al 2011 ) are characterised by a high intracellular concentration of porphyrins. These porphyrins were represented by a mixture of uroporphyrin III and coproporphyrin III and their methyl esters, with cytoplasmic and membrane localisation (Nikitushkin et al 2016 ). These dormant forms were sensitive to illumination with 395-, 475- and 575-nm light, which decreased the CFU by approximately 3 log10 (Shleeva et al 2019 ).…”

Section: Endogenous Photosensitisers For Antimycobacterial Pdimentioning

confidence: 99%

Photoinactivation of mycobacteria to combat infection diseases: current state and perspectives

Shleeva

Savitsky

Kaprelyants

2021

Appl Microbiol Biotechnol

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The spread of multi-drug-resistant bacterial strains causing serious infectious diseases dictates the development of new approaches to combat these diseases. In addition to drug resistance, the important causative agent of tuberculosis (Mycobacterium tuberculosis (Mtb)) is able to persist asymptomatically in individuals for many years, causing latent forms of tuberculosis. In such a dormant state, Mtb cells are also resistant to known antibiotics. In this regard, photodynamic inactivation (PDI) could be an effective alternative to antibiotics as its action is based on the generation of active forms of oxygen independently on the presence of specific antibiotic targets, thereby inactivating both drug-resistant and dormant bacteria. In this review, we summarise examples of the application of PDI for the elimination of representatives of the genus Mycobacteria, both in vitro and in vivo. According to published results, including photosensitisers in the PDI regime results in a significantly higher lethal effect. Such experiments were mainly performed using chemically synthesised photosensitisers, which need to be transported to the areas of bacterial infections, limiting PDI usage by surface (skin) diseases. In this regard, endogenous photosensitisers (mainly porphyrins) could be used to solve the problem of transportation. In vitro experiments demonstrate the effective application of PDI for mycobacteria, including Mtb, using endogenous porphyrins; the intracellular contents of these substances can be elevated by administration of 5-aminolevulenic acid, a precursor of porphyrin synthesis. Photodynamic inactivation can also be used for dormant mycobacteria, which are characterised by high levels of endogenous porphyrins. Thus, PDI can effectively eliminate drug-resistant mycobacteria. The exploitation of modern light-transmitting techniques opens new possibilities to use PDI in clinical settings. Key points•The potential effects of photodynamic inactivation of mycobacteria are critically reviewed.•Approaches to photoinactivation of mycobacteria using exogenous and endogenous photosensitisers are described.•Prospects for the use of photodynamic inactivation in the treatment of tuberculosis are discussed.

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“…It can be assumed that the effect of complete elimination of dormant, "non-culturable" bacteria can be accomplished by factors which produce indirect, harmful effects on bacteria (Kaprelyants et al, 2018). In this regard, we employed a previously discovered phenomenon of the accumulation of free and methylated porphyrins in dormant mycobacteria (Nikitushkin et al, 2016). This finding made it possible to induce the PDI of mycobacteria (Shleeva et al, 2019b(Shleeva et al, , 2020.…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, application of physical factors seems to be promising in order to destroy metabolically passive dormant bacterial forms. Recently we found that significant concentrations of the intermediates participating in protoporphyrin biosynthesis were present in dormant forms of M. smegmatis (Nikitushkin et al, 2016), a fast-growing bacterium which is genetically close to M. tuberculosis, These findings suggested that dormant bacteria may be killed by photodynamic inactivation (PDI) when fluorescent porphyrins serve as intracellular photosensitizers. Studies have also demonstrated the photoinactivation of dormant mycobacterial forms in vitro in the rapidly growing, tuberculosis-related pathogenic strain, M. smegmatis (Shleeva et al, 2019b(Shleeva et al, , 2020.…”

Section: Introductionmentioning

confidence: 99%

Corynebacterium jeikeium Dormant Cell Formation and Photodynamic Inactivation

2020

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Pathogenic non-spore forming bacteria enter a dormant state under stressful conditions, which likely allows them to acquire resistance to various antibiotics. This work revealed the efficient formation of dormant “non-culturable” (NC) Corynebacterium jeikeium cells in stationary phase upon gradual acidification of the growth medium. Such cells were unable to form colonies and existed in a prolonged stationary phase. At an early stage of dormancy (approximately 14 days post-inoculation), dormant cells are able for resuscitation in liquid medium. However, those stored for long time in dormant state needed addition of supernatant taking from active C. jeikeium cultures for successful resuscitation. NC cells possessed low RNA synthesis and significant tolerance to antibiotics (rifampicin and vancomycin). They also accumulated free porphyrins, and 5-aminolevulinic acid addition enhanced free porphyrin accumulation which makes them potentially sensitive to photodynamic inactivation (PDI). PDI of dormant bacteria was accomplished by exposing cells to a 565 nm wavelength of light using a SOLIS-4C light-emitting diode for 60 min. This revealed that increased porphyrin concentrations were correlated with elevated PDI sensitivity. Results shown here demonstrate the potential utility of employing PDI to minimize levels of dormant, persistent corynebacteria and the C. jeikeium dormancy model developed here may be useful for finding new drugs and techniques for combatting persistent corynebacteria.

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The main pigment of the dormantMycobacterium smegmatisis porphyrin

Cited by 29 publications

References 17 publications

Protein Composition of Mycobacterium smegmatis Differs Significantly Between Active Cells and Dormant Cells With Ovoid Morphology

Protein Composition of Mycobacterium smegmatis Differs Significantly Between Active Cells and Dormant Cells With Ovoid Morphology

Photoinactivation of mycobacteria to combat infection diseases: current state and perspectives

Corynebacterium jeikeium Dormant Cell Formation and Photodynamic Inactivation

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