Methylation of Coproporphyrin as a Protective Mechanism in Mycobacteria under Adverse Conditions

IF 0.7 Q4 CHEMISTRY, MULTIDISCIPLINARY Moscow University Chemistry Bulletin Pub Date : 2024-06-04 DOI:10.3103/s0027131424700068

D. I. Bagaeva, G. R. Demina, M. O. Agaphonov, A. P. Savitsky, A. S. Kaprelyants, M. O. Shleeva

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Abstract

The transition of active Mycolicibacterium smegmatis cells to a dormant state under acidification conditions is accompanied by the intracellular accumulation of tetramethyl ester of coproporphyrin (TMC). At the same time, the dormant forms of mycobacteria develop resistance to a number of damaging factors. The addition of 5-aminolevulinic acid (ALA), a precursor of porphyrin synthesis, into the bacterial culture medium leads to the accumulation of TMC in actively growing cells, which simulates the situation with dormant mycobacteria. Upon threefold increasing the concentration of TMC, the bacteria become sevenfold more resistant to the action of 40 mM hydrogen peroxide and 90-fold more resistant to heating up to 80°C. At the same time, in M. smegmatis cells with an increased concentration of TMC, the activity of dichlorophenolindophenol reductase that is a marker of respiratory chain activity decreases by 18%. The detected inhibition of activity can lead to a decrease in side oxidative reactions in the cell. Therefore, the accumulation of methylated coproporphyrin is possibly one of the mechanisms for the development of mycobacterium resistance at dormancy.

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卟啉的甲基化是分枝杆菌在不利条件下的一种保护机制

摘要在酸化条件下，活跃的烟曲霉菌（Mycolicibacterium smegmatis）细胞向休眠状态的转变伴随着共卟啉四甲酯（TMC）在细胞内的积累。同时，处于休眠状态的分枝杆菌会对一些破坏性因子产生抗性。在细菌培养基中加入卟啉合成的前体--5-氨基乙酰丙酸（ALA），会导致生长活跃的细胞中 TMC 的积累，这模拟了休眠分枝杆菌的情况。将 TMC 的浓度提高三倍后，细菌对 40 毫摩尔过氧化氢的抗性提高了七倍，对加热至 80°C 的抗性提高了 90 倍。同时，在 TMC 浓度增加的 M. smegmatis 细胞中，作为呼吸链活性标志的二氯苯酚靛酚还原酶的活性降低了 18%。检测到的活性抑制可导致细胞内的副氧化反应减少。因此，甲基化共卟啉的积累可能是分枝杆菌在休眠期产生抗药性的机制之一。

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来源期刊

Moscow University Chemistry Bulletin CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

1.30

自引率

14.30%

发文量

期刊介绍： Moscow University Chemistry Bulletin is a journal that publishes review articles, original research articles, and short communications on various areas of basic and applied research in chemistry, including medical chemistry and pharmacology.