In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 7 ( 2022-7-11), p. e1010660-
Abstract:
Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which is featured by its ability to replicate in acid vacuoles resembling the lysosomal network. One key virulence determinant of C . burnetii is the Dot/Icm system that transfers more than 150 effector proteins into host cells. These effectors function to construct the lysosome-like compartment permissive for bacterial replication, but the functions of most of these effectors remain elusive. In this study, we used an affinity tag purification mass spectrometry (AP-MS) approach to generate a C . burnetii -human protein-protein interaction (PPI) map involving 53 C . burnetii effectors and 3480 host proteins. This PPI map revealed that the C . burnetii effector CBU0425 (designated CirB) interacts with most subunits of the 20S core proteasome. We found that ectopically expressed CirB inhibits hydrolytic activity of the proteasome. In addition, overexpression of CirB in C . burnetii caused dramatic inhibition of proteasome activity in host cells, while knocking down CirB expression alleviated such inhibitory effects. Moreover, we showed that a region of CirB that spans residues 91–120 binds to the proteasome subunit PSMB5 (beta 5). Finally, PSMB5 knockdown promotes C . burnetii virulence, highlighting the importance of proteasome activity modulation during the course of C . burnetii infection.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010660
DOI:
10.1371/journal.ppat.1010660.g001
DOI:
10.1371/journal.ppat.1010660.g002
DOI:
10.1371/journal.ppat.1010660.g003
DOI:
10.1371/journal.ppat.1010660.g004
DOI:
10.1371/journal.ppat.1010660.g005
DOI:
10.1371/journal.ppat.1010660.g006
DOI:
10.1371/journal.ppat.1010660.g007
DOI:
10.1371/journal.ppat.1010660.g008
DOI:
10.1371/journal.ppat.1010660.g009
DOI:
10.1371/journal.ppat.1010660.s001
DOI:
10.1371/journal.ppat.1010660.s002
DOI:
10.1371/journal.ppat.1010660.s003
DOI:
10.1371/journal.ppat.1010660.s004
DOI:
10.1371/journal.ppat.1010660.s005
DOI:
10.1371/journal.ppat.1010660.s006
DOI:
10.1371/journal.ppat.1010660.s007
DOI:
10.1371/journal.ppat.1010660.s008
DOI:
10.1371/journal.ppat.1010660.s009
DOI:
10.1371/journal.ppat.1010660.s010
DOI:
10.1371/journal.ppat.1010660.s011
DOI:
10.1371/journal.ppat.1010660.s012
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
