Metabolism of bacteria
Our body fights pathogens with an arsenal of methods. For example, a diseased cell restricts its magnesium supply to keep intruders at bay. Here is a special "pump" in important cells, as researchers from the University of Basel have now shown.
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Basel / Switzerland – When pathogens invade the body, it immediately triggers the immune system to fight the bacteria. To avoid patrolling cells patrolling, some bacteria nest in host cells. But the host has developed strategies to control the germs hidden inside the cell.
Such as prof. Dirk Bumann and his team at the University of Basel Biozentrum have now discovered that magnesium is key to the growth of bacteria in the cell. Magnesium deficiency means stress for bacteria. Pathogens stop growing and multiplying. To create this magnesium deficiency, the host cell uses a special pump: the transport protein NRAMP1.
The magnesium pump stops pathogens
"It has long been known that NRAMP1 is associated with resistance to infection. But how and why they have never been clear," says Bumann. Therefore, in their study, researchers examined salmonella, which causes, among other things, gastrointestinal influenza and typhoid fever. They nest in small inclusions in the phagocytes of the immune system.
Whether and how quickly salmonella multiplies in inclusive and eventually spreads depends greatly on the functionality of the NRAMP1 transporter. "We were surprised by the fact that this transport protein removes magnesium ions from cellular inclusions and keeps Salmonella so calm. This is a completely new, unexpected mechanism," commented the study leader.
Magnesium as Achilles' heel
Magnesium is a key component of many metabolic enzymes, so when it is lacking, bacteria slow down metabolism and slow down their growth. "Magnesium is an Achilles heel for intracellular pathogens. The less they thirst, the more thirsty it is. The bacteria are on standby and in turn activate all magnesium imaging systems. Still, they fail enough," explains Bumann's colleague and first author Oliver Cunrath. "However, if the pump is defective in the host cells, Salmonella has enough magnesium to grow rapidly."
The transporter affects the host resistance
The functionality of NRAMP1 is reflected in susceptibility to infection. Animals and humans with low NRAMP1 levels are more sensitive to various intracellular agents. If this transmission is completely missing, the infection is fatal even for a very small number of pathogens.
It is not an option to deny pathogens through a diet low in magnesium because humans also depend on magnesium, which fulfills many important metabolic functions. But you could also disrupt the magnesium balance of bacteria with new drugs and slow down pathogens even more. This would give the patient a decisive advantage in defeating the infection.
Original issues: Olivier Cunrath and Dirk Bumann: SLC11A1 Host Resistance Factor Limits Salmonella Growth Due to Magnesium Deprivation, Science, November 22, 2019, vol. 366, no. 6468, p. 995-999; Doi: 10.1126 / science.aax7898
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