Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

Proteolysis in dairy lactic acid bacteria has been studied in great detail by genetic, biochemical and ultrastructural methods. From these studies the picture emerges that the proteolytic systems of lactococci and lactobacilli are remarkably similar in their components and mode of action. The proteolytic system consists of an extracellularly located serine-proteinase, transport systems specific for di-tripeptides and oligopeptides (> 3 residues), and a multitude of intracellular peptidases. This review describes the properties and regulation of individual components as well as studies that have led to identification of their cellular localization. Targeted mutational techniques developed in recent years have made it possible to investigate the role of individual and combinations of enzymes in vivo. Based on these results as well as in vitro studies of the enzymes and transporters, a model for the proteolytic pathway is proposed. The main features are: (i) proteinases have a broad specificity and are capable of releasing a large number of different oligopeptides, of which a large fraction falls in the range of 4 to 8 amino acid residues; (ii) oligopeptide transport is the main route for nitrogen entry into the cell; (iii) all peptidases are located intracellularly and concerted action of peptidases is required for complete degradation of accumulated peptides.

Towards the reconstruction of the genome-scale metabolic model of Lactobacillus acidophilus La-14

Lactobacillus acidophilus is a probiotic lactic acid bacterium used in food and dietary supplements for many years. However, despite its importance for industrial development and recognized health-promoting effects, no genome-scale metabolic model has been reported. A GSM model for L. acidophilus La-14 was developed, accounting 494 genes and 783 reactions. A genome annotation was performed to identify the metabolic potential of the bacterium. The biomass composition was determined based on information available in literature and previously published models. The model was validated by comparing in silico simulations with experimental data, regarding the aerobic and anaerobic growth. The reconstruction of the metabolic model has confirmed the fastidious requirements of L. acidophilus for amino acids, fatty acids, and vitamins. This model can be used for a better understanding of the metabolism of this bacterium and identification of industrially desirable compounds.This study was performed under the scope of the project “BIODATA.PT – Portuguese Biological Data Network” (ref. LISBOA-01-0145-FEDER-022231), funded by FCT/MCTES, through national funds of PIDDAC, Fundo Europeu de Desenvolvimento Regional (FEDER), Programa Operacional de Competitividade e Internacionalização (POCI) and Programa Operacional Regional de Lisboa (Lisboa 2020).info:eu-repo/semantics/publishedVersio

Effectiveness of a self-management training for patients with chronic and treatment resistant anxiety or depressive disorders on quality of life, symptoms, and empowerment : results of a randomized controlled trial

Background: Anxiety and depressive disorders are common mental disorders. A substantial part of patients does not achieve symptomatic remission after treatment in specialized services. Current care as usual (CAU) for these patients consists of long-term supportive contacts. Termination of CAU is often not considered to be an option due to persistent symptoms, a low level of functioning, and the absence of further treatment options. A new intervention, ZemCAD, offers a program focused on rehabilitation and self-management, followed by referral back to primary care. Methods: This multicenter randomized controlled trial was carried out in twelve specialized outpatient mental health care services in the Netherlands. Consenting and eligible patients were invited for the MINI interview and the baseline questionnaire. Assessments were done at 6 (T1), 12 (T2) and 18 (T3) months post baseline. We used linear mixed model analysis (LMM) to ascertain the effectiveness of the ZemCAD group relative to the CAU group on quality of life, symptom severity and empowerment. Results: In total 141 patients were included. The results at 18-month follow-up regarding to quality of life and symptom severity, showed no significant differences between the ZemCAD group and the CAU group, except on the 'social relationships'-domain (d = 0.37). With regard to empowerment a significant difference between both groups was observed in the total empowerment score and one empowerment dimension (d = 0.45 and d = 0.39, respectively). After the ZemCAD intervention, more patients went from specialized outpatient mental health services back to a less specialized health care setting with less intensive treatment, such as primary care. Conclusion: The findings in this study suggest that patients with chronic and treatment-resistant anxiety and depression using the ZemCAD intervention improve on empowerment but not on symptom severity or quality of life. Since little is known about the effects of rehabilitation and self-management in patients with chronic and treatment resistant anxiety and depressive disorders, this is a first attempt to provide a proof-of-concept study in this under-researched but important field. Trial registration: Netherlands Trial Register: NTR3335, registered 7 March 2012

Purification and characterization of the mature, membrane-associated cell- envelope proteinase of Lactobacillus helveticus L89

Lactobacillus helveticus L89 possesses a cell-envelope proteinase (Lb- CEP) that is biochemically and genetically related to that of the lactococci (Lc-CEP). The in-situ proteinase is resistant to autoproteolysis and remains associated with the membrane during lysozyme treatment of cells and subsequent mechanical disruption of the treated cells. The proteinase was purified from isolated membranes by a procedure that preserves the complete in-situ proteinase (mature proteinase) assumed to be the N-terminally processed translation product including the membrane anchor: its monomer molecular mass is approximately 180 kDa. The purified enzyme appeared to be more stable towards heat than hitherto known related, but C-terminally truncated cell-envelope proteinases of lactobacilli and lactococci, which were released from the cells by autoproteolysis. On the basis of its specificity towards caseins, towards the α(s1)-casein-(1-23)-fragment and towards two differently charged chromophoric peptides, the proteinase was recognized as an (Lb-)CEP(1/1H) mixed-type variant different from those identified so far among the lactococcal proteinases.M. C. M.-H. wishes to acknowledge financial support by the Direcci6n General de Investigacidn Cientffica y T4cnica (Ministerio de Educación y Ciencia). Her stay at NIZO as a visiting scientist was under the terms of research projects ALI 91-0387 (granted by the Comisidn Interministerial de la Ciencia y Tecnologia) and ECLAIR (AGRE-CT91-0064) (DTEE).Peer Reviewe