RT Journal Article
SR Electronic
T1 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
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 202598
DO 10.1101/202598
A1 Bennett H. Penn
A1 Zoe Netter
A1 Jeffrey R. Johnson
A1 John Von Dollen
A1 Gwendolyn M. Jang
A1 Tasha Johnson
A1 Yamini M. Ohol
A1 Cyrus Maher
A1 Samantha L. Bell
A1 Kristina Geiger
A1 Xiaotang Du
A1 Alex Choi
A1 Trevor Parry
A1 Mayumi Naramura
A1 Chen Chen
A1 Stefanie Jaeger
A1 Michael Shales
A1 Dan A. Portnoy
A1 Ryan Hernandez
A1 Laurent Coscoy
A1 Jeffery S. Cox
A1 Nevan J. Krogan
YR 2017
UL http://biorxiv.org/content/early/2017/10/17/202598.abstract
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.