New discoveries by Cambridge scientists about a molecular waste-disposal process that ‘eats’ bacteria are influencing the clinical management of cystic fibrosis, and could be the basis of innovative new treatments to fight off bacteria. Broken pieces of internal structures, damaged organelles and harmful clumps of proteins are all examples of the molecular detritus that builds up continuously in our cells. Fortunately, we are equipped with an intracellular process called autophagy (literally ‘self-eating’) that gathers up the debris, wraps it in a double membrane and delivers it to an intracellular sac called the lysosome. Here, the material is ingested, digested and recycled, ready to be used again.
Image credit: University of Edinburgh, Wellcome Images, Wellcome Library, London
Recent work has suggested that autophagy may also be important in killing intracellular bacteria that are able to escape the normal processes that control infection within cells. Autophagy appears to be critical in controlling infections of Mycobacterium tuberculosis (MTB) and related species called non-tuberculous mycobacteria (NTM), which are able to block degradation by lysosomes and thereby replicate within cells.
Researchers working at the University’s Cambridge Institute for Medical Research (CIMR) and Papworth Hospital have noticed that patients with chronic lung diseases such as cystic fibrosis (CF) are becoming increasingly infected with a highly pathogenic, multi-drug-resistant (MDR) NTM called Mycobacterium abscessus. Their research, published recently in the Journal of Clinical Investigation, suggests that M. abscessus infection may be linked to long-term use of azithromycin, an antibiotic with anti-inflammatory properties. They propose that azithromycin blocks autophagy in a type of white blood cell called the macrophage, effectively tipping the balance in favour of the Mycobacterium surviving in the cell.