PT  - JOURNAL ARTICLE
AU  - Bennett H. Penn
AU  - Zoe Netter
AU  - Jeffrey R. Johnson
AU  - John Von Dollen
AU  - Gwendolyn M. Jang
AU  - Tasha Johnson
AU  - Yamini M. Ohol
AU  - Cyrus Maher
AU  - Samantha L. Bell
AU  - Kristina Geiger
AU  - Xiaotang Du
AU  - Alex Choi
AU  - Trevor Parry
AU  - Mayumi Naramura
AU  - Chen Chen
AU  - Stefanie Jaeger
AU  - Michael Shales
AU  - Dan A. Portnoy
AU  - Ryan Hernandez
AU  - Laurent Coscoy
AU  - Jeffery S. Cox
AU  - Nevan J. Krogan
TI  - An <em>Mtb</em>-Human Protein-Protein Interaction Map Reveals that Bacterial LpqN Antagonizes CBL, a Host Ubiquitin Ligase that Regulates the Balance Between Anti-Viral and Anti-Bacterial Responses
AID  - 10.1101/202598
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 202598
4099  - http://biorxiv.org/content/early/2017/10/17/202598.short
4100  - http://biorxiv.org/content/early/2017/10/17/202598.full
AB  - Although macrophages are armed with potent anti-bacterial 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 a systematic 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 new 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 anti-bacterial and anti-viral immunity. Collectively, these findings illustrate the utility of this Mtb-human PPI map as a resource for developing a deeper understanding of the intricate interactions between Mtb and its host.