Diseases like tuberculosis, leprosy and various infections are caused due to Mycobacteria. Mycobacteria is a candidate of pathogenic bacteria that harms people with negotiated immune systems. Although, Mycobacteria survive by switching between two different types of metabolism. EPFL scientists have found that a volume control mechanism can control this switching. The mechanism continuously adjusts itself to meet the bacterium’s survival needs.
Lead author Paul Murima (EPFL) said, “It is like a thermostat that controls a home’s heating system in response to temperature fluctuations. If the temperature goes high, a thermostat cools the house down. If it gets too low it heats it up. Similarly, the mechanism that controls how isocitrate is used responds to negative feedback, and so it dampens ‘noise’ to maintain optimal levels.”
Mycobacteria generate energy by metabolizing fats through the biochemical reactions cycle. This cycle also generates a molecule that the bacterium can take away to use anywhere. Thus, it stops the energy-producing cycle. Scientists have discovered that mycobacteria can switch between these two routes through a volume control mechanism. It can also improve their survival.
Once the isocitrate molecule has been produced, it can pass in two directions. 1. Continue the energy production cycle or 2. It was taken away to synthesize other parts of the bacterium. If it goes through the biosynthesis direction exceptionally, it might restore or stop the energy production cycle. Devastating though it sounds, this can excellently treat an infecting mycobacterium.
The key to controlling which route isocitrate will manifest in the enzymes surrounding all these reactions. The enzyme isocitrate dehydrogenase keeps it for the fat metabolism and energy production cycle. Similarly, the enzymes isocitrate lyase and malate synthase switch it away into biosynthetic processes in the bacterium.
Scientists then observed how mycobacteria activate or inactivate the genes of these enzymes. They used the gene deletion technique to remove a particular gene in a bacterial strain and analyze the consequences. Scientists are also able to generate various strains of mycobacteria through this method. They did not use any of the genes that code for the enzymes of interest for this.
Thus, the conclusion is, through the volume control mechanism, the mycobacterium decides where to direct isocitrate.
The mechanism is appropriately adaptable and flexible. It responds instantly to active environments in which the bacterium can find itself. Additionally, it is also unique from that used by gut bacteria. It does not affect a patient’s microbiome. (Microbiome’s increasing evidence shows that it is intimately linked to the healthy function of the immune system.)