During the course of infection, Mycobacterium tuberculosis (Mtb) is exposed to diverse redox stresses that trigger metabolic and physiological changes. How these stressors are sensed and relayed to the Mtb transcriptional apparatus remains unclear. Here, we provide evidence that WhiB6 differentially regulates the ESX-1 and DosR regulons through its Fe-S cluster. When challenged with NO, WhiB6 continually activates expression of the DosR regulons but regulates ESX-1 expression through initial activation followed by gradual inhibition. Comparative transcriptomic analysis of the holo- and reduced apo-WhiB6 complemented strains confirms these results and also reveals that WhiB6 controls aerobic and anaerobic metabolism, cell division, and virulence. Using the Mycobacterium marinum zebrafish infection model, we find that holo- and apo-WhiB6 modulate levels of mycobacterial infection, granuloma formation, and dissemination. These findings provide fresh insight into the role of WhiB6 in mycobacterial infection, dissemination, and disease development.

Numerous previous studies have investigated the mental health status of medical staff in China and explored its associated determinate factors; however, scope and methods associated with these have introduced uncertainty regarding the results. The aim of this study was to perform a comprehensive examination of the mental health status of Chinese medical staff and its relative risk factors based on a cross-sectional survey.We conducted a broad area, cross-sectional, questionnaire-based survey of Chinese medical workers. Participants were randomly selected from 27 hospitals in the Heilongjiang province. The questionnaire that was distributed consisted of 5 parts: the demographic characteristics of the participant; questions related to the relative risk factors of psychological health; the posttraumatic stress disorder (PTSD) Checklist-Civilian Version (PCL-C); the Self-rating Depression Scale (SDS); and the Self-rating Anxiety Scale (SAS). The last 3 components were used to evaluate the mental health status of the target population. Logistic and linear regression were used to analyze the determinate factors of the mental health status of Chinese medical staff.Of the 1679 questionnaires distributed, 1557 medical workers responded (response rate: 92.73%; male: 24.1%; female 75.9%). The results of mental health status self-assessments indicated that 32.3% of participants were considered to have some degree of PTSD (based on the PCL-C). The SDS index was 0.67 and the mean score from SAS was 55.26; a result higher than found in the general population. Multivariate logistic regression analysis revealed that being female, dissatisfaction or average satisfaction with income, and good or very good self-perceived psychological endurance when faced with an emergency were associated with a reduction of PTSD symptoms. A frequency of verbal abuse incidents greater than 4 was associated with an increase in PTSD symptoms.The mental health status of Chinese medical staff is poor. While the determinate factors based on different measurement standards were not completely consistent, the overlapping major risk factors identified that influenced psychological health were the amount of education, the perceived level of respect, and psychological endurance.

Mycobacterium tuberculosis adopts various strategies to cope with oxidative stress during infection. Transcriptional regulators, including σ factors, make important contributions to this stress response, but how these proteins cooperate with each other is largely unknown. In this study, the role of RbpA and its cooperation with σ factors in response to oxidative stress are investigated. Knock down expression of rbpA in Mycobacterium smegmatis attenuated bacterial survival in the presence of H2 O2 . Additionally, transcription of the rbpA gene was induced by H2 O2 in a σ(E) -dependent manner. After induction, RbpA interacts with the principal sigma factor, σ(A) , to control the transcription of furA-katG operon, which encodes an H2 O2 scavenging enzyme. Moreover, this regulation is responsible for the role of σ(E) in oxidative response because bacterial survival was attenuated and transcription of the furA-katG operon was down-regulated with H2 O2 treatment in sigE deletion mutant (ΔsigE), and over-expression of RbpA in ΔsigE strain restored all of these phenotypes. Taken together, our study first illustrated a mechanism for σ(E) in response to oxidative stress through regulation of rbpA transcription. This study was also the first to demonstrate that RbpA is required for the full response to oxidative stress by cooperating with the principal σ(A) .

Gene transcription catalysed by RNA polymerase is regulated by transcriptional regulators, which play central roles in the control of gene transcription in both eukaryotes and prokaryotes. In regulating gene transcription, many regulators form dimers that bind to DNA with repeated motifs. However, some regulators function as monomers, but their mechanisms of gene expression control are largely uncharacterized. Here we systematically characterized monomeric versus dimeric regulators in the tuberculosis causative agent Mycobacterium tuberculosis. Of the .160 transcriptional regulators annotated in M. tuberculosis, 154 transcriptional regulators were tested, 22 % probably act as monomers and most are annotated as hypothetical regulators. Notably, all members of the WhiB-like protein family are classified as monomers. To further investigate mechanisms of monomeric regulators, we analysed the actions of these WhiB proteins and found that the majority interact with the principal sigma factor s A , which is also a monomeric protein within the RNA polymerase holoenzyme. Taken together, our study for the first time globally classified monomeric regulators in M. tuberculosis and suggested a mechanism for monomeric regulators in controlling gene transcription through interacting with monomeric sigma factors.