For their own self-preservation, infected bacteria often try their best to stay out of the immune system in our bodies – and scientists have found a surprising and previously undiscovered way to do this.
What happens is that the bacteria release toxins to disarm the mitochondria in immune cells, those small organelles that act as the engine compartment of cells. Once the immune cells feel that their mitochondria are inactive, they trigger apoptosis as programmed cells die.
The findings could give us new ways to tackle infected bacteria, especially those that are resistant to growing antibiotics – although so far, experiments have only been performed on mice in the laboratory.
“Ironically, it is the activation of dead host cell factors that deliver the definitive battle to mitochondria that induce apoptosis, not the bacterial toxins themselves,” says molecular biologist Pankaj Deo of the Monash Biomedicine Discovery Institute (MBDI). in Australia.
In other words, the bacterial toxins do not directly kill immune cells, but rather set in motion a chain of events that cause the body’s emergency responders to kill themselves. Our immune cells use mitochondria as infection sensors.
This was the case in tests on mice described in this study: by focusing on genetic controls for rodent apoptosis, the scientists were able to reduce inflammation in the animals and reduce the risk of infection.
The bacterial pathogens Neisseria gonorrhoeae, uropathogenic Escherichia coli, en Pseudomonas aeruginosa were the tests – all of which are often found in hospitals and may develop resistance to drugs – but the team says the findings would also apply to other types of bacteria.
“We have shown in this paper that we can accelerate the immune response,” says molecular biologist Thomas Naderer of MBDI.
“The other side is that if that response persists and we get constant inflammation – which is normally associated with bacterial infection and which causes a lot of tissue damage – we have a new way to stop this tissue-damaging inflammation. “
Previously, attention was focused on bacterial toxins that caused another type of automatic cell death, called pyroptosis. Here, the researchers found other mitochondria-directed toxins that are entangled in structures called outer membrane vesicles.
Now that we know more about how the mitochondria are targeted, scientists might be able to stop it. Further trials will be needed on humans to work out exactly what is happening at the microorganism level, but it is possible that existing drugs may be re-examined and new drugs may be developed to combat infection.
With pathogens getting worse and smarter when it comes to evading the drugs we send to defeat them – such as defending the body’s own defenses – any new innovations in treatment would make a significant difference can make.
“A lot of effort has been put into blocking endotoxins that kill immune cells, but this study really shifted the focus to various toxins that may be more important,” says Naderer. “It gives us some good leads that we can see as a next step.”
The study was published in Natural microbiology.
.
