A protein-protein interaction map reveals that the Coxiella burnetii effector CirB inhibits host proteasome activity.

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.

Mental Health Differences in Healthcare Workers Exposed to Different Risks During the Coronavirus Disease 2019 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused a significant impact on the physical and mental health of healthcare workers. This study assessed the psychological status of healthcare workers who were exposed to different risk-levels in China and explored the factors that affected their mental health. Methods: Demographic, occupational characteristics, and mental health measurements were collected from 810 workers in 41 hospitals in China, through online questionnaires from February 11 to March 3, 2020. The degree of symptoms for fatigue, anxiety, and insomnia were assessed using the Chinese versions of the Fatigue Severity Scale, 7-item Generalized Anxiety Disorder Scale, and Insomnia Severity Index, respectively. Binary logistic regression analysis was performed to identify factors associated with mental health symptoms. Results: All 810 participants completed the relevant questionnaires without missing data. The prevalence of fatigue, anxiety, and insomnia symptoms was 74.3, 73.7, and 61.7%, respectively. Nurses, women, and workers exposed to high-risk areas were more likely to report mental health problems (P < 0.05). After controlling for confounders, exposure to high-risk areas was independently associated with increased symptoms of fatigue, anxiety, and insomnia (fatigue among high-risk areas: OR, 3.87; 95% CI, 2.26-6.61; P < 0.001; anxiety among high-risk areas: OR, 2.66; 95% CI, 1.58-4.51; P < 0.001; insomnia among high-risk areas: OR, 2.83; 95% CI, 1.68-4.79, P < 0.001). Conclusion: The study demonstrated significant differences in psychological symptoms among healthcare workers exposed to different levels of risk, and those in high-risk areas were more vulnerable to experiencing mental health symptoms. These findings emphasize the importance of giving due attention to healthcare workers, especially women, nurses, and those working in high-risk settings during the COVID-19 pandemic.