Department of Molecular and Cell Biology, Division of Biochemistry, Biophysics and Structural Biology, University of California, Berkeley, Berkeley, United States
Caleb Cassidy-Amstutz
Department of Molecular and Cell Biology, Division of Biochemistry, Biophysics and Structural Biology, University of California, Berkeley, Berkeley, United States
Matthew Knight
Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, United States
Rahul Singh
Department of Microbiology and Immunology, The University of British Columbia, Vancouver, Canada
Lindsay D Eltis
Department of Microbiology and Immunology, The University of British Columbia, Vancouver, Canada
Department of Molecular and Cell Biology, Division of Biochemistry, Biophysics and Structural Biology, University of California, Berkeley, Berkeley, United States
Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, United States; School of Public Health, Division of Infectious Diseases and Vaccinology, University of California, Berkeley, Berkeley, United States
Encapsulin nanocompartments are an emerging class of prokaryotic protein-based organelle consisting of an encapsulin protein shell that encloses a protein cargo. Genes encoding nanocompartments are widespread in bacteria and archaea, and recent works have characterized the biochemical function of several cargo enzymes. However, the importance of these organelles to host physiology is poorly understood. Here, we report that the human pathogen Mycobacterium tuberculosis (Mtb) produces a nanocompartment that contains the dye-decolorizing peroxidase DyP. We show that this nanocompartment is important for the ability of Mtb to resist oxidative stress in low pH environments, including during infection of host cells and upon treatment with a clinically relevant antibiotic. Our findings are the first to implicate a nanocompartment in bacterial pathogenesis and reveal a new mechanism that Mtb uses to combat oxidative stress.
