Pseudomonas aeruginosa N-3-Oxo-Dodecanoyl-Homoserine Lactone Impacts Mitochondrial Networks Morphology, Energetics, and Proteome in Host Cells.

Mitochondria play crucial roles in cellular metabolism, signaling, longevity, and immune defense. Recent evidences have revealed that the host microbiota, including bacterial pathogens, impact mitochondrial behaviors and activities in the host. The pathogenicity of Pseudomonas aeruginosa requires quorum sensing (QS) cell-cell communication allowing the bacteria to sense population density and collectively control biofilm development, virulence traits, adaptation and interactions with the host. QS molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C12-HSL), can also modulate the behavior of host cells, e.g., epithelial barrier properties and innate immune responses. Here, in two types of cells, fibroblasts and intestinal epithelial cells, we investigated whether and how P. aeruginosa 3O-C12-HSL impacts the morphology of mitochondrial networks and their energetic characteristics, using high-resolution transmission electron microscopy, fluorescence live-cell imaging, assay for mitochondrial bioenergetics, and quantitative mass spectrometry for mitoproteomics and bioinformatics. We found that 3O-C12-HSL induced fragmentation of mitochondria, disruption of cristae and inner membrane ultrastructure, altered major characteristics of respiration and energetics, and decreased mitochondrial membrane potential, and that there are distinct cell-type specific details of these effects. Moreover, this was mechanistically accompanied by differential expression of both common and cell-type specific arrays of components in the mitochondrial proteome involved in their structural organization, electron transport chain complexes and response to stress. We suggest that this effect of 3O-C12-HSL on mitochondria may represent one of the events in the interaction between P. aeruginosa and host mitochondria and may have an impact on the pathogens strategy to hijack host cell activities to support their own survival and spreading.

People with gambling disorder and risky alcohol habits benefit more from motivational interviewing than from cognitive behavioral group therapy.

Background. Effective psychological treatment, including cognitive behavioral therapy and motivational interviewing (MI), is available for people with problematic gambling behaviors. To advance the development of treatment for gambling disorder, it is critical to further investigate how comorbidity impacts different types of treatments. The purpose of this study was to investigate whether screening for risky alcohol habits can provide guidance on whether people with gambling disorder should be recommended cognitive behavioral group therapy (CBGT) or MI. Methods. The present study is a secondary analysis of a previous randomized controlled trial that compared the effects of CBGT, MI and a waitlist control group in the treatment of disordered gambling. Assessment and treatment was conducted at an outpatient dependency clinic in Stockholm, Sweden, where 53 trial participants with gambling disorder began treatment. A modified version of the National Opinion Research Centre DSM-IV Screen for gambling problems was used to assess gambling disorder. The Alcohol Use Disorders Identification Test (AUDIT) was used to screen for risky alcohol habits. Results. The interaction between treatment and alcohol habits was significant and suggests that patients with gambling disorder and risky alcohol habits were better helped by MI, while those without risky alcohol habits were better helped by CBGT. Conclusions. The results support a screening procedure including the AUDIT prior to starting treatment for gambling disorder because the result of the screening can provide guidance in the choice of treatment. Patients with gambling disorder and risky alcohol habits are likely to be best helped if they are referred to MI, while those without risky alcohol habits are likely to be best helped if they are referred to CBGT.

Motivational interviewing versus cognitive behavioral group therapy in the treatment of problem and pathological gambling: a randomized controlled trial.

Pathological gambling is a widespread problem with major implications for society and the individual. There are effective treatments, but little is known about the relative effectiveness of different treatments. The aim of this study was to test the effectiveness of motivational interviewing, cognitive behavioral group therapy, and a no-treatment control (wait-list) in the treatment of pathological gambling. This was done in a randomized controlled trial at an outpatient dependency clinic at Karolinska Institute (Stockholm, Sweden). A total of 150 primarily self-recruited patients with current gambling problems or pathological gambling according to an NORC DSM-IV screen for gambling problems were randomized to four individual sessions of motivational interviewing (MI), eight sessions of cognitive behavioral group therapy (CBGT), or a no-treatment wait-list control. Gambling-related measures derived from timeline follow-back as well as general levels of anxiety and depression were administered at baseline, termination, and 6 and 12 months posttermination. Treatment showed superiority in some areas over the no-treatment control in the short term, including the primary outcome measure. No differences were found between MI and CBGT at any point in time. Instead, both MI and CBGT produced significant within-group decreases on most outcome measures up to the 12-month follow-up. Both forms of intervention are promising treatments, but there is room for improvement in terms of both outcome and compliance.