Autophagy Shown to Have Key Role in Controlling Infection

According to researchers at the Francis Crick Institute, autophagy, the body’s process of removing old and damaged cell parts, is also an essential part of tackling infections that take hold within our cells. They believe that if this natural process can be harnessed with new treatments, it could present an alternative to, or improve use of antibiotics, especially where bacteria have become resistant to existing drugs.

In their study, published in Nature Microbiology, the team studied genes key to bacteria’s ability to evade autophagy. First, they engineered macrophages from induced pluripotent stem cells. They then used genome-editing tools to manipulate the macrophages ability to perform autophagy. When genes key to autophagy were removed and the cells were infected with Mycobacterium tuberculosis, the bacterial infection took hold, replicating more within the engineered cells and causing mass host cell death.

These results are evidence for a strong role of autophagy in controlling intracellular infections like tuberculosis. If this pathway can be boosted or strengthened, it could be a new avenue for tackling antibiotic resistance, by making existing antibiotic drugs more effective or presenting an alternative to drugs in cases where bacteria have evolved resistance.

The team is now planning to screen for drug compounds that could be used to boost autophagy in a targeted way. “Boosting the autophagy pathway isn’t as simple as it might seem,” explains senior author Max Gutierrez. “This is because all parts of the body use autophagy as a way to recycle old and damaged cells. In order to safely increase autophagy in the location of infections, we need to target the pathway in macrophages alone.”