January 17, 2020—Ludwig Oxford adjunct Pedro Moura Alves demonstrates that drugs used to treat TB interact with the Aryl hydrocarbon receptor to worsen treatment outcomes.
Antibiotic resistance is an increasingly prevalent and serious global health problem, particularly in tuberculosis (TB), which is the leading cause of mortality by a single infectious agent (World Health Organisation). Scientists are therefore trying to come up with alternative strategies for treatment of multi-drug resistant bacteria, including targeting factors that regulate the body’s defences. One potential target is the Aryl hydrocarbon receptor (AhR), which is known to sense molecules produced by the bacterium that causes TB in humans, Mycobacterium tuberculosis (Moura Alves et al Nature 2014). In this publication in Cell Host and Microbe, Pedro Moura Alves and Stefan Kaufmann (Max Planck Institute for Infection Biology, Berlin) show that common drugs used to treat TB interact with AhR, causing an impairment of the body’s defences as well as reduced drug availability. They demonstrate that inhibiting AhR in combination with a TB drug, rifampicin, increases the efficacy of therapy in zebrafish model of mycobacterial infection. This research suggests that targeting AhR in conjunction with standard TB drugs would be an effective new strategy for treating TB.