Aldrich Lab Researches Mycobacterium Abscessus
March 13, 2023
Research continues in collaboration with researchers at Harvard Medical School
Mycobacterium abscessus is an opportunistic pathogen that causes severe lung infections, particularly in patients with underlying lung disorders such as cystic fibrosis or chronic pulmonary disease and is intrinsically resistant to most antibiotics. The high pH in the airway lumen environment serves as a natural barrier, inhibiting the growth of many inhaled pathogens, yet M. abscessus primarily colonizes this environment.
Eric Rubin and colleagues at Harvard Medical School in collaboration with Courtney Aldrich at the University of Minnesota report in Nature Microbiology a realistic air–liquid interface culture system for M. abscessus infection and identify genes essential for growth in this unique environment using TnSeq. Genes involved in biotin biosynthesis were the most upregulated and biotin was subsequently shown to be required to support fatty acid remodeling and envelope fluidity of the bacterium in the alkaline lung environment. A small-molecule inhibitor of biotin biosynthesis developed by Qiang Liu in the Aldrich lab was found to be active in the lung infection model providing hope for a new treatment of one of the most difficult-to-treat bacterial pathogens.
Sullivan, M. R.; McGowen, K.; Liu, Q.; Akusobi, C.; Young, D. C.; Mayfield, J. A.; Raman, S.; Wolf, I. D.; Moody, D. B.; Aldrich, C. C.; Muir, A.; Rubin, E. J., Biotin-dependent cell envelope remodelling is required for Mycobacterium abscessus survival in lung infection. Nat Microbiol 2023,8 (3), 481-497.