July 29, 2021

Human cells use detergent-like protein to kill bacteria


An antimicrobial protein produced by normal body cells destroys the fat-like components of the bacterial cell wall, just as washing-active substances do with fat stains.

The ingredients contained in detergents have an antimicrobial effect in addition to their fat-dissolving ones: they penetrate the lipid layer of cell membranes and can thus kill viruses and bacteria. Now, American doctors have discovered that bacteria that have invaded human cells trigger the production of a protein that works in a similar way against the pathogens.

Supported by other antibacterial factors, the apolipoprotein APOL3 destroys the double membrane of the cell wall of salmonella and other gram-negative bacteria, the researchers report in the journal “Science”. A better understanding of this form of so-called cell-autonomous immune defense, which functions independently of immune cells, could help to develop new therapies against infections.

“In this case, humans produce their own antibiotic in the form of a protein that acts like a detergent,” says John MacMicking of Yale University in New Haven. When pathogens enter our body, they trigger alarm signals that activate the immune system.

On the other hand, one of the messenger substances, interferon gamma, also switches on numerous genes of normal body cells, whereby these cells set their own defense mechanisms in motion. While skin and mucosal cells release antimicrobial peptides to attack pathogens outside the cells, it requires other defenses when bacteria have already penetrated the cell interior.

Using human cell cultures, MacMicking and his colleagues investigated which genes are activated by interferon gamma. One of the approximately 19,000 identified genes caused the production of the apolipoprotein APOL3 in cells of different tissues. As with a detergent, the molecular structure of this protein showed a water-soluble and a fat-soluble section.

With the fat-soluble molecular part, the protein can penetrate into the fat-like lipid layer of biological membranes, which causes the decay of the membrane structure. With the help of special techniques of live microscopy, the researchers were also able to make this directly visible when they infected cells with Salmonella (Salmonella enterica serovar Typhimurium).

After damage to the outer bacterial membrane by other factors, APOL3 broke down the inner membrane into small pieces. However, the cell must protect its own membranes: The cholesterol content typical only for human membranes and certain bacterial membrane components ensure that the attack is only directed against the bacteria. APOL3 was only effective against those gram-negative bacteria that enter the cytoplasm of body cells during the course of infection.

“The results confirm the view that every cell in the body can be a part of the immune system,” says Carl Nathan of Weill Cornell Medical College, commenting on the research. The dissolution of the cell membrane is – in addition to the perforation of the membrane, starvation and poisoning – one of the few methods to kill pathogens. Further research could enable new therapies that support the body’s natural immune response to infections. This would be all the more important as more and more pathogens have become resistant to the available antibiotics.