Salmonella, other bacteria use ‘hack’ to turn immune system against our body: ‘It’s kind of ingenious’

Not even super heroes could have the ability to outwit bacteria. According to researchers at the University of California – Davis Health, some bacteria, such as salmonella, have developed a mechanism that lets them evade destruction entirely by the immune system.

Andreas Bäumler, vice-chair of research and professor in the Department of Medical Microbiology and Immunology at UC Davis School of Medicine, explains the adaptive mechanism within host cells. “The Salmonella outmaneuvers host defenses by using one of our best weapons and turning it against us. It is kind of ingenious,” he says in a university release.

Macrophages are a part of the human immune system responsible for cleaning up disease-causing bacteria and cellular debris. The macrophages directly kill bacteria by engulfing them, or targets them for destruction by other immune cells. The dead host cell then tricks other, still-living macrophages into becoming the new hosts for the pathogens.

Macrophages only live about 30 days, however, so intracellular bacteria like Salmonella must periodically find new host cells. They need to do so without being detected and destroyed by the immune system.

Bacteria Use Virulence Factors

Bacteria have learned to survive when encased in a membrane-enclosed vacuole within the macrophage. The enclosed bacteria avoid detection by other immune cells, such as bacteria-killing neutrophils. 

The researchers found that the bacteria which have infected a macrophage use weapons — virulence factors — to create holes in the membranes of both the vacuole and the macrophage. The factors trigger the cells’ death, and open channels for spread of the infection. The bacteria also activate the complement aspect of the immune system, generating a “find-me” signal to attract neutrophils. 

When a neutrophil arrives to clean up the dead macrophage with the Salmonella inside, it engulfs both the dead macrophage and the pathogen  in a process called efferocytosis. The dead macrophage shields the Salmonella from the antimicrobial properties of the neutrophil, allowing the bacteria to survive. 

Salmonella is just one type of intracellular bacteria that can cause disease in people. Some other pathogens that live inside cells include Brucella abortus, Listeria monocytogenesChlamydia trachomatisCoxiella burnetii and Mycobacterium tuberculosis.

The researchers demonstrated that Brucella uses the same mechanism as Salmonella to evade the host immune system, suggesting that this virulence strategy may be shared by other bacterial pathogens that can live within host cells.

Beware of Antibiotic Resistance

Some of these bacterial infections may resolve on their own, but they often require treatment with antibiotics. In the coming decades, antibiotic resistance is expected to increase significantly, meaning that the antibiotics available may no longer be effective against intracellular bacteria.

“Multi-drug resistance is on the rise, and by 2050, multi-drug resistant bacteria are projected to be the number one cause of death. This is why we need to understand these diseases – to find a vulnerability in their mechanisms of action. Once you understand the mechanism, you may be able to develop a new target treatment,” says Bäumler.

The study is published in the journal Cell Host & Microbe.


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