Bacteria make up some of the most important organisms in the world that entire ecosystems depend on. However, harmful species can cause severe illnesses, especially antibiotic-resistant bacteria. In a recent discovery, a team from the Monash Biomedicine Discovery Institute found a way that bacteria evade the body's immune responses.
The new study is published in the journal Nature Microbiology. The scientists hope their findings can help develop new ways to treat bacterial infections, which continue to evolve and mutate to become antibiotic-resistant.
Some of the deadliest antibiotic-resistant bacteria include Staphylococcus aureus, Mycobacterium tuberculosis, Enterobacteriaceaie in gut bacteria, and many others. These harmful bacteria cause a range of infections like staph infections in the skin, organ infections, and various other conditions.
Bacteria typically attach to a host and release toxins that attack cells in the immune system by disabling mitochondria, or a cell's source of power. The harmful organisms can also rapidly multiply to disrupt normal tissue functions or cause immune system functions to become toxic.
Focusing on Cell Mitochondria
When immune cells detect that their mitochondria are no longer working against bacteria infections, it triggers apoptosis or 'cellular suicide.' Dr. Pankaj Deo explained that 'ironically, it is the activation of host cell death factors that deliver the final blow to mitochondria which induces apoptosis, not the bacterial toxins themselves.'
Genetically targeting cell apoptosis factors can reduce inflammation. Dr. Deo's team observed that in mice models, their health outcomes increased when they targeted treating the cell mitochondria instead of focusing on bacteria.
The scientists tested several pathogens, including Escherichia coli, Neisseria gonorrhoeae, and Pseudomonas aeruginosa, which is a multi-drug resistant species commonly found in hospitals. The same methods can be applied to many other bacterial species as well, explained Dr. Deo.
Alongside co-author Dr. Thomas Naderer, they realized that their findings open the way for developing new therapies against antibiotic-resistant bacteria. "There's been a lot of effort trying to block endotoxins that kill immune cells, but this study really shifts the focus onto different toxins that might be more important," said Dr. Naderer.
Their research can help determine the next steps in dealing with bacterial infections. This is especially important since scientists have not been able to develop new antibiotics in the past 30 years.
Their experiments not only show how to fight bacterial infections effectively, but they have also found a way to accelerate the immune response by focusing on inflammation, said Dr. Naderer. 'The other side is that if that response persists and we get constant inflammation - which is usually associated with bacterial infection and which causes a lot of tissue damage - we have a new way to shut down that tissue-damaging inflammation.'
Previously, explained Dr. Deo, scientists thought that bacteria releasing endotoxins would cause immune cells to have an inflammatory response until cells die in a process called pyroptosis. They discovered that pathogenic bacteria release additional toxins called outer membrane vesicles. The toxins attack immune cell mitochondria and disable them, eventually causing apoptosis.
The team will be working on drug treatments that are currently being developed. They also hope to repurpose existing drug treatments such as anti-cancer medication to see if they can fight bacterial infections more effectively.
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