A previously unknown method used by bacteria to evade immune responses has been discovered by the scientists at Monash Biomedicine Discovery Institute (BDI).
Bacterial infections, which are becoming increasingly resistant to antibiotics could be prevented with the help of this new study published in Nature Microbiology.
To understand the process by which bacteria release toxins that disarm the ‘power-house’ mitochondria in immune cells, Dr. Pankaj Deo and his colleagues in Dr. Thomas Naderer’s laboratory took a different approach.
The study shows that immune cells with dysfunctional mitochondria during infection triggers apoptosis. Dr. Pankaj said that it is the activation of host cell death factors that deliver the final blow to mitochondria which induces apoptosis, not the bacterial toxins themselves.
The researchers were able to reduce inflammation in mice by genetically targeting apoptotic factors, which improved health outcomes.
They used multidrug-resistant bacteria like the deadly Pseudomonas aeruginosa, uropathogenic Escherichia coli, and Neisseria gonorrhoeae, which are found prevalent in hospitals. But the results would apply to other bacterial species also.
New therapeutic possibilities could be opened up by targeting mitochondria to understand the new ways some bacterial infections evade the immune response, said Dr. Naderer, who led the research.
Scientists had been
trying to block endotoxins that kill immune cells for a long time, but this study shifts the focus to some other toxins that are more important.The scientists show in this research that they can accelerate the immune response to bacterial infections and that they have a way to shut down the tissue-damaging inflammation if the response persists, leading to constant inflammation and a lot of tissue damage.
It was previously believed that endotoxins released by bacteria induce an inflammatory type of programmed cell death called pyroptosis in immune cells. The new study proves that a similar mechanism is used by pathogenic bacteria to release additional toxins. Small surface structures called outer membrane vesicles released by those bacteria, packaging toxins that target mitochondria, kill immune cells. The mitochondria die by apoptosis or cellular suicide after becoming disarmed and dysfunctional. This is how the bacteria evade immune responses.
Scientists will now focus on investigating or repurposing the drugs already in use, perhaps as anti-cancer drugs, to test if they can clear bacterial infections.
