Carbon Sources Tune Antibiotic Susceptibility in Pseudomonas aeruginosa via Tricarboxylic Acid Cycle Control.

Metabolically dormant bacteria present a critical challenge to effective antimicrobial therapy because these bacteria are genetically susceptible to antibiotic treatment but phenotypically tolerant. Such tolerance has been attributed to impaired drug uptake, which can be reversed by metabolic stimulation. Here, we evaluate the effects of central carbon metabolite stimulations on aminoglycoside sensitivity in the pathogen Pseudomonas aeruginosa. We identify fumarate as a tobramycin potentiator that activates cellular respiration and generates a proton motive force by stimulating the tricarboxylic acid (TCA) cycle. In contrast, we find that glyoxylate induces phenotypic tolerance by inhibiting cellular respiration with acetyl-coenzyme A diversion through the glyoxylate shunt, despite drug import. Collectively, this work demonstrates that TCA cycle activity is important for both aminoglycoside uptake and downstream lethality and identifies a potential strategy for potentiating aminoglycoside treatment of P. aeruginosa infections

SARS-CoV-2 seroprevalence in healthcare workers of a Swiss tertiary care centre at the end of the first wave: A cross-sectional study

Objective To assess the SARS-CoV-2 transmission in healthcare workers (HCWs) using seroprevalence as a surrogate marker of infection in our tertiary care centre according to exposure. Design Seroprevalence cross-sectional study. Setting Single centre at the end of the first COVID-19 wave in Lausanne, Switzerland. Participants 1874 of 4074 responders randomly selected (46% response rate), stratified by work category among the 13 474 (13.9%) HCWs. Main outcome measures Evaluation of SARS-CoV-2 serostatus paired with a questionnaire of SARS-CoV-2 acquisition risk factors internal and external to the workplace. Results The overall SARS-CoV-2 seroprevalence rate among HCWs was 10.0% (95% CI 8.7% to 11.5%). HCWs with daily patient contact did not experience increased rates of seropositivity relative to those without (10.3% vs 9.6%, respectively, p=0.64). HCWs with direct contact with patients with COVID-19 or working in COVID-19 units did not experience increased seropositivity rates relative to their counterparts (10.4% vs 9.8%, p=0.69 and 10.6% vs 9.9%, p=0.69, respectively). However, specific locations of contact with patients irrespective of COVID-19 status - in patient rooms or reception areas - did correlate with increased rates of seropositivity (11.9% vs 7.5%, p=0.019 and 14.3% vs 9.2%, p=0.025, respectively). In contrast, HCWs with a suspected or proven SARS-CoV-2-infected household contact had significantly higher seropositivity rates than those without such contacts (19.0% vs 8.7%, p<0.001 and 42.1% vs 9.4%, p<0.001, respectively). Finally, consistent use of a mask on public transportation correlated with decreased seroprevalence (5.3% for mask users vs 11.2% for intermittent or no mask use, p=0.030). Conclusions The overall seroprevalence was 10% without significant differences in seroprevalence between HCWs exposed to patients with COVID-19 and HCWs not exposed. This suggests that, once fully in place, protective measures limited SARS-CoV-2 occupational acquisition within the hospital environment. SARS-CoV-2 seroconversion among HCWs was associated primarily with community risk factors, particularly household transmission. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

SARS-CoV-2 seroprevalence in healthcare workers of a Swiss tertiary care centre at the end of the first wave: a cross-sectional study.

To assess the SARS-CoV-2 transmission in healthcare workers (HCWs) using seroprevalence as a surrogate marker of infection in our tertiary care centre according to exposure. Seroprevalence cross-sectional study. Single centre at the end of the first COVID-19 wave in Lausanne, Switzerland. 1874 of 4074 responders randomly selected (46% response rate), stratified by work category among the 13 474 (13.9%) HCWs. Evaluation of SARS-CoV-2 serostatus paired with a questionnaire of SARS-CoV-2 acquisition risk factors internal and external to the workplace. The overall SARS-CoV-2 seroprevalence rate among HCWs was 10.0% (95% CI 8.7% to 11.5%). HCWs with daily patient contact did not experience increased rates of seropositivity relative to those without (10.3% vs 9.6%, respectively, p=0.64). HCWs with direct contact with patients with COVID-19 or working in COVID-19 units did not experience increased seropositivity rates relative to their counterparts (10.4% vs 9.8%, p=0.69 and 10.6% vs 9.9%, p=0.69, respectively). However, specific locations of contact with patients irrespective of COVID-19 status-in patient rooms or reception areas-did correlate with increased rates of seropositivity (11.9% vs 7.5%, p=0.019 and 14.3% vs 9.2%, p=0.025, respectively). In contrast, HCWs with a suspected or proven SARS-CoV-2-infected household contact had significantly higher seropositivity rates than those without such contacts (19.0% vs 8.7%, p<0.001 and 42.1% vs 9.4%, p<0.001, respectively). Finally, consistent use of a mask on public transportation correlated with decreased seroprevalence (5.3% for mask users vs 11.2% for intermittent or no mask use, p=0.030). The overall seroprevalence was 10% without significant differences in seroprevalence between HCWs exposed to patients with COVID-19 and HCWs not exposed. This suggests that, once fully in place, protective measures limited SARS-CoV-2 occupational acquisition within the hospital environment. SARS-CoV-2 seroconversion among HCWs was associated primarily with community risk factors, particularly household transmission