Research Reveals How Some Bacteria Counteract Defense Mechanisms of Human Cells

British scientists have identified a way in which Salmonella, the bacteria that cause typhoid fever and gastroenteritis, inactivate immune defenses in human cells.

This image shows Salmonella bacteria, green, invading a human red blood cell (Kieran McGourty et al / Imperial College London)

One way in which human cells fight off infections is by engulfing the smaller bacterial cells and then attacking them with toxic enzymes contained in small packets called lysosomes. Lysosomes constantly need to be replenished with fresh enzymes that are generated from a factory within human cells. These enzymes are carried from the factory along a dedicated transport pathway. After dropping off new enzymes at lysosomes, the transport carriers are sent back to the factory to pick up new enzymes.

A study, published in the journal Science, shows that Salmonella protects itself from this attack by depleting the supply of toxic enzymes. The researchers found that after Salmonella bacteria have been engulfed by the cell, but before they are killed, Salmonella injects a protein that prevents the cell from recycling the transport carriers between the factory and the lysosome.

This means that Salmonella effectively cuts off the supply line of the enzymes that would otherwise kill it. As a result, the enzymes get re-routed out of the cell and the lysosomes lose their potency. Salmonella is then able to exploit the disarmed lysosomes by feeding off the nutrients they contain.

“This seems to be a very effective way for these harmful bacteria to interfere with our cell’s defense mechanisms, and then exploit the defective lysosomes to their own benefit,” explained Prof David Holden of the Imperial College London’s Department of Medicine and MRC Center for Molecular Bacteriology and Infection, senior author of the study.

“Our challenge now is to understand in greater detail how the injected Salmonella protein works at the molecular level, and to exploit our findings to develop more effective vaccines. This is especially important since many Salmonella strains are now resistant to antibiotics,” Prof Holden concluded.

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Bibliographic information: Kieran McGourty et al. Salmonella Inhibits Retrograde Trafficking of Mannose-6-Phosphate Receptors and Lysosome Function. Science, vol. 338, no. 6109, pp. 963-967; doi: 10.1126/science.1227037