A Trinity research team has uncovered a new method of increasing the effectiveness of an antimicrobial drug used in the fight against tuberculosis.
Published this week in the prestigious International Journal of Molecular Sciences, researchers led by Prof Joseph Keane and Dr James Phelan of the Trinity School of Medicine demonstrated that by treating macrophages – a type of white blood cell that engulf and destroy pathogens – with an iron chelator, desferrioxamine (DFX), the effectiveness of an important anti-tuberculosis drug can be improved.
Dr Phelan has shown in past research that DFX can support the lungs’ immune response against tuberculosis by supporting a key stage of cellular respiration known as glycolysis. Now, the team has demonstrated the iron-chelating agent’s ability to improve the immune response of individual cells.
After adding DFX to macrophages infected with tuberculosis and treating the cells with bedaquiline, which is used for multi-drug resistant forms of tuberculosis, the researchers observed an increase in the ability of the white blood cells to fight the infection, observing lower rates of infection in cells treated with DFX on top of bedaquiline than in the cells treated only with the traditional tuberculosis drug.
This research has important implications for the treatment of tuberculosis nationally and internationally. While it has not received the same level of attention as the coronavirus, in 2020 tuberculosis caused the deaths of 1.8 million people (compared to 2.68 million from the coronavirus).
Even more worrying, the underlying bacteria which causes tuberculosis continues to mutate and become resistant to the antibacterial medications we use to treat it.
In Ireland, the first case of a Bedaquiline-resistant (the drug used for multi-resistant infections studied in this research) tuberculosis case was reported last year. Additionally, the drug regimen required for fighting resistant strains can lead to unbearable side effects, which result in a low rate of people who follow through with their prescribed doses.
This increases the risk of new drug-resistant strains because an unfinished dose allows for certain bacteria with better survival genes to survive and replicate.
Thus, treatments like this which focus on improving the immune response instead of killing the pathogen are needed in order to stay ahead of the bacteria’s mutations.
In a press statement, Phelan noted that “the use of iron binders could help pave the way for the development of new host-directed-therapies,” adding that they have the potential to “drastically improve the treatment and clinical care for patients”.
