Structural architecture of TolQ-TolR inner membrane protein complex from opportunistic pathogen Acinetobacter baumannii.

Gram-negative bacteria harness the proton motive force (PMF) within their inner membrane (IM) to uphold the integrity of their cell envelope, an indispensable aspect for both division and survival. The IM TolQ-TolR complex is the essential part of the Tol-Pal system, serving as a conduit for PMF energy transfer to the outer membrane. Here we present cryo-EM reconstructions of Acinetobacter baumannii TolQ in apo and TolR- bound forms at atomic resolution. The apo TolQ configuration manifests as a symmetric pentameric pore, featuring a trans-membrane funnel leading towards a cytoplasmic chamber. In contrast, the TolQ-TolR complex assumes a proton non-permeable stance, characterized by the TolQ pentamer's flexure to accommodate the TolR dimer, where two protomers undergo a translation-based relationship. Our structure-guided analysis and simulations support the rotor-stator mechanism of action, wherein the rotation of the TolQ pentamer harmonizes with the TolR protomers' interplay. These findings broaden our mechanistic comprehension of molecular stator units empowering critical functions within the Gram-negative bacterial cell envelope. Teaser: Apo TolQ and TolQ-TolR structures depict structural rearrangements required for cell envelope organization in bacterial cell division.

Long-term health outcomes of Q-fever fatigue syndrome patients.

This study determined long-term health outcomes (≥10 years) of Q-fever fatigue syndrome (QFS). Long-term complaints, health-related quality of life (HRQL), health status, energy level, fatigue, post-exertional malaise, anxiety, and depression were assessed. Outcomes and determinants were studied for the total sample and compared among age subgroups: young (<40years), middle-aged (≥40-<65years), and older (≥65years) patients. 368 QFS patients were included. Participants reported a median number of 12.0 long-term complaints. Their HRQL (median EQ-5D-5L index: 0.63) and health status (median EQ-VAS: 50.0) were low, their level of fatigue was high, and many experienced post-exertional malaise complaints (98.9%). Young and middle-aged patients reported worse health outcomes compared with older patients, with both groups reporting a significantly worse health status, higher fatigue levels and anxiety, and more post-exertional malaise complaints and middle-aged patients having a lower HRQL and a higher depression risk. Multivariate regression analyses confirmed that older age is associated with better outcomes, except for the number of health complaints. QFS has thus a considerable impact on patients' health more than 10 years after infection. Young and middle-aged patients experience more long-term health consequences compared with older patients. Tailored health care is recommended to provide optimalcare for each QFS patient.

The prolonged impact of COVID-19 on symptoms, health-related quality of life, fatigue and mental well-being: a cross-sectional study.

Background: A subset of patients experience persisting symptoms after an acute COVID-19 infection, referred to as "post COVID-19 condition". This cross-sectional study aimed to compare symptoms, health-related quality of life (HRQoL), fatigue, mental well-being, and determinants of diminished HRQoL, between patients with post COVID-19 condition categorized by time since acute infection. Methods: We performed an online survey and analyzed responses of 10,194 adult respondents with a confirmed or suspected COVID-19 infection, who experienced persisting symptoms ≥3 months after the initial infection. The most debilitating symptoms and health outcomes were studied separately for respondents 3-6, 7-9, 10-12, 13-18, 19-24, and >24 months after acute infection. Results: At each time period, fatigue, sensory-processing problems, and concentration problems were the most debilitating symptoms reported by respondents, although the proportion of respondents who reported these symptoms differed significantly between time periods. Respondents 3-6 months post-acute infection had the lowest HRQoL (median EQ-5D utility score: 0.59), the highest fatigue level (median score: 110.0) and the highest proportion with a likely depressive disorder (32.4%), whereas respondents 13-18 months post-infection had the highest HRQoL (0.65), the lowest fatigue level (106.0), and the second lowest proportion with a likely depressive disorder (25.0%) (p = 0.000-0.007). Compared to those 13-18 and 19-24 months post-infection, respondents >24 months post-infection had a slightly lower HRQoL (0.60), lower fatigue level (108.0), and lower proportion with a likely depressive disorder (29.2%), although only the differences in HRQoL were statistically significant (p = 0.001-0.010). Younger age, female gender, lower level of education, not having paid work before COVID-19, comorbidity, and not being vaccinated, seemed to be associated with lower HRQoL. Conclusion: Regardless of time since infection, respondents considered fatigue, sensory processing problems and concentration problems the most debilitating symptoms. They experienced a low HRQoL and severe fatigue, even more than two years after acute COVID-19 infection. Respondents 3-6 months post-infection had the worst health outcomes, whereas respondents 13-18 months post-infection had the best outcomes, indicating that, at least for a subgroup of patients, health status may improve over time.