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Mol Cell. 2018 Aug 16;71(4):637-648.e5. doi: 10.1016/j.molcel.2018.07.010.

An Mtb-Human Protein-Protein Interaction Map Identifies a Switch between Host Antiviral and Antibacterial Responses.

Author information

1
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
2
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94148, USA; Gladstone Institutes, San Francisco, CA 94158, USA.
3
Department of Microbiology and Immunology, Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, CA 94158, USA.
4
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA.
5
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska, Omaha, NE 68182, USA.
6
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; School of Public Health, University of California, Berkeley, Berkeley, CA 94720, USA.
7
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Microbiology and Immunology, Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: jeff.cox@berkeley.edu.
8
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94148, USA; Gladstone Institutes, San Francisco, CA 94158, USA. Electronic address: nevan.krogan@ucsf.edu.

Abstract

Although macrophages are armed with potent antibacterial functions, Mycobacterium tuberculosis (Mtb) replicates inside these innate immune cells. Determinants of macrophage intrinsic bacterial control, and the Mtb strategies to overcome them, are poorly understood. To further study these processes, we used an affinity tag purification mass spectrometry (AP-MS) approach to identify 187 Mtb-human protein-protein interactions (PPIs) involving 34 secreted Mtb proteins. This interaction map revealed two factors involved in Mtb pathogenesis-the secreted Mtb protein, LpqN, and its binding partner, the human ubiquitin ligase CBL. We discovered that an lpqN Mtb mutant is attenuated in macrophages, but growth is restored when CBL is removed. Conversely, Cbl-/- macrophages are resistant to viral infection, indicating that CBL regulates cell-intrinsic polarization between antibacterial and antiviral immunity. Collectively, these findings illustrate the utility of this Mtb-human PPI map for developing a deeper understanding of the intricate interactions between Mtb and its host.

KEYWORDS:

Cbl; LpqN; host-pathogen interaction; macrophage; mycobacterium; protein-protein interaction; tuberculosis; ubiquitin

PMID:
30118682
PMCID:
PMC6329589
[Available on 2019-08-16]
DOI:
10.1016/j.molcel.2018.07.010
[Indexed for MEDLINE]

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