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

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.