Researchers from the Monash Biomedicine Discovery Institute have discovered a method used by bacteria to develop antibiotic resistance and evade immune responses. The research may point to new ways to treat antibiotic-resistant bacterial infections.
In the study, the researchers found that bacteria release toxins that disarm the mitochondria of immune cells. These immune cells then sense their mitochondria are no longer able to work during infection, something that then triggers apoptosis, also known as cell death.
Ironically, first author of the study, Dr. Pankaj Deo, says that, contrary to popular belief, it is the activation of factors within the host's cell that leads to its death as opposed to the bacterial toxins themselves. To test this theory, however, the researchers then decided to target these apoptotic factors in immune cells in mouse models to see whether they could stop the process in its tracks.
In doing so, they were able to reduce inflammation in mice, which in turn went on to improve their health outcomes. Although they focused on just three bacterial pathogens (including the deadly Pseudomonas aeruginosa, found in hospitals and is known to be resistant to multiple antibiotics), the researchers say that their findings could also be applied to other species of bacteria.
"What scientists have thought before is that when endotoxins (part of the cell wall of Gram-negative bacteria) are released by bacteria, they induce an inflammatory type of programmed cell death called pyroptosis in immune cells." says Dr. Deo.
"We've found that the pathogenic bacteria use a similar mechanism to release additional toxins. They kill immune cells by releasing small surface structures called outer membrane vesicles—packages of toxins that target mitochondria. The mitochondria are disarmed, become dysfunctional then die according to apoptosis or cellular suicide."
The researchers now aim to investigate the potential of existing drugs that target the apoptotic response to see if they can be repurposed for bacterial infections.