10.7272/Q6JQ0Z6J
Budzik, Jonathan M
0000-0001-8025-7911
University of California, San Francisco
Swaney, Danielle L
0000-0001-6119-6084
University of California, San Francisco
Jimenez-Morales, David
University of California, San Francisco
Johnson, Jeffrey R
University of California, San Francisco
Garelis, Nicholas E
University of California, Berkeley
Repasy, Teresa
University of California, Berkeley
Roberts, Allison W
0000-0001-6681-4144
University of California, Berkeley
Popov, Lauren M
University of California, Berkeley
Parry, Trevor J
University of California, Berkeley
Pratt, Dexter
University of California, San Diego
Ideker, Trey
University of California, San Diego
Krogan, Nevan J
University of California, San Francisco
Cox, Jeffery S
0000-0002-5061-6618
University of California, Berkeley
Dynamic post-translational modification profiling of M.
tuberculosis-infected primary macrophages
Dryad
dataset
2020
Mycobacterium tuberculosis
Macrophages
National Institute of Allergy and Infectious Diseases
https://ror.org/043z4tv69
U19 AI106754
National Institute of Allergy and Infectious Diseases
https://ror.org/043z4tv69
R01 AI120694
National Institute of Allergy and Infectious Diseases
https://ror.org/043z4tv69
1K08AI146267
National Institute of Allergy and Infectious Diseases
https://ror.org/043z4tv69
DP1 AI124619
National Institute of Allergy and Infectious Diseases
https://ror.org/043z4tv69
P01 AI063302
Cystic Fibrosis Foundation
https://ror.org/00ax59295
Harry Shwachman Award
National Institute of General Medical Sciences
https://ror.org/04q48ey07
P50 GM082250
2020-01-30T00:00:00Z
2020-01-30T00:00:00Z
en
https://doi.org/10.7554/elife.51461
157012175 bytes
3
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
Macrophages are highly plastic cells with critical roles in immunity,
cancer, and tissue homeostasis, but how these distinct cellular fates are
triggered by environmental cues is poorly understood. To uncover how
primary murine macrophages respond to bacterial pathogens, we globally
assessed changes in post-translational modifications of proteins during
infection with Mycobacterium tuberculosis, a notorious intracellular
pathogen. We identified hundreds of dynamically regulated phosphorylation
and ubiquitylation sites, indicating that dramatic remodeling of multiple
host pathways, both expected and unexpected, occurred during infection.
Most of these cellular changes were not captured by mRNA profiling, and
included activation of ubiquitin-mediated autophagy, an evolutionarily
ancient cellular antimicrobial system. This analysis also revealed that a
particular autophagy receptor, TAX1BP1, mediates clearance of
ubiquitylated Mtb and targets bacteria to LC3-positive phagophores. These
studies provide a new resource for understanding how macrophages shape
their proteome to meet the challenge of infection.
Immunofluorescence microscopy images were obtained with the Opera Phenix
(Perkin Elmer) at 63X magnification. Immunoblot images were obtained with
a Li-Cor Odyssey instrument.
Please see the manuscript file for details about staining protocols.