Increased bile resistance in Salmonella enterica mutants lacking Prc periplasmic protease

Prc is a periplasmic protease involved in processing of penicillin-binding protein 3 (PBP3). Lack of Prc suppressesbile sensitivity in Dam-, Wec-, PhoP-, DamX-, and SeqA- mutants of Salmonella enterica, and increases bile resistance in thewild type. Changes in the activity of penicillin binding proteins PBP3, PBP4, PBP5/6 and PBP7 are detected in a Prc-background, suggesting that peptidoglycan remodeling might contribute to bile resistance. [Int Microbiol 2013; 16(2):87-92]Keywords: Salmonella; bile; Prc protease; peptidoglycan; penicillin-binding protein

Draft genome sequence of the bacteriocinogenic strain Enterococcus faecalis DBH18, isolated from mallard ducks (Anas platyrhynchos)

Here, we report the draft genome sequence of Enterococcus faecalis DBH18, a bacteriocinogenic lactic acid bacterium (LAB) isolated from mallard ducks (Anas platyrhynchos). The assembly contains 2,836,724 bp, with a G+C content of 37.6%. The genome is predicted to contain 2,654 coding DNA sequences (CDSs) and 50 RNAs

IL-3 or IL-7 Increases ex Vivo Gene Transfer Efficiency in ADA-SCID BM CD34 + Cells while Maintaining in Vivo Lymphoid Potential

To improve maintenance and gene transfer of human lymphoid progenitors for clinical use in gene therapy of adenosine deaminase (ADA)-deficient SCID we investigated several gene transfer protocols using various stem cell-enriched sources. The lymphoid differentiation potential was measured by an in vitro clonal assay for B/NK cells and in the in vivo SCID-hu mouse model. Ex vivo culture with the cytokines TPO, FLT3-ligand, and SCF (T/F/S) plus IL-3 or IL-7 substantially increased the yield of transduced bone marrow (BM) CD34+ cells purified from ADA-SCID patients or healthy donors, compared to T/F/S alone. Moreover, the use of IL-3 or IL-7 significantly improved the maintenance of in vitro B cell progenitors from ADA-SCID BM cells and allowed the efficient transduction of B and NK cell progenitors. Under these optimized conditions transduced CD34+ cells were efficiently engrafted into SCID-hu mice and gave rise to B and T cell progeny, demonstrating the maintenance of in vivo lymphoid reconstitution capacity. The protocol based on the T/F/S + IL-3 combination was included in a gene therapy clinical trial for ADA-SCID, resulting in long-term engraftment of stem/progenitor cells. Remarkably, gene-corrected BM CD34+ cells obtained from one patient 4 and 11 months after gene therapy were capable of repopulating the lymphoid compartment of SCID-hu hosts

Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling

This work was funded by grants PID2020-112971GB-I00/10.13039/501100011033 (F.G-dP.) and PID2019-104070RB-C21 (S.V.) of the Spanish Ministry of Science and Innovation, VR2018-02823 of the Swedish Research Council (F.C.), KAW2012.0184 of the Knut and Alice Wallenberg Foundation (F.C.), and SMK2062 of the Kempe Foundation (F.C.

The MACC-II 2007–2008 reanalysis: atmospheric dust evaluation and characterization over northern Africa and the Middle East

In the present work, atmospheric mineral dust from a MACC-II short reanalysis run for 2 years (2007–2008) has been evaluated over northern Africa and the Middle East using satellite aerosol products (from MISR, MODIS and OMI satellite sensors), ground-based AERONET data, in situ PM10 concentrations from AMMA, and extinction vertical profiles from two ground-based lidars and CALIOP satellite-based lidar. The MACC-II aerosol optical depth (AOD) spatial and temporal (seasonal and interannual) variability shows good agreement with those provided by satellite sensors. The capability of the model to reproduce the AOD, Ångström exponent (AE) and dust optical depth (DOD) from daily to seasonal time-scale is quantified over 26 AERONET stations located in eight geographically distinct regions by using statistical parameters. Overall DOD seasonal variation is fairly well simulated by MACC-II in all regions, although the correlation is significantly higher in dust transport regions than in dust source regions. The ability of MACC-II in reproducing dust vertical profiles has been assessed by comparing seasonal averaged extinction vertical profiles simulated by MACC-II under dust conditions with corresponding extinction profiles obtained with lidar instruments at M'Bour and Santa Cruz de Tenerife, and with CALIOP.This work has been supported by EU-project Monitoring Atmospheric Composition and Climate (MACC-II) under the European Union Seventh Framework Programme, grant agreement number 283576. J. M. Baldasano and S. Basart acknowledge the Severo Ochoa (SEV-2011-00067) program of the Spanish Government and the mobility program from the Catalan Government (BE-DGR 2012)

Shared midgut binding sites for Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac and Cry1Fa proteins from Bacillus thuringiensis in two important corn pests, Ostrinia nubilalis and Spodoptera frugiperda

First generation of insect-protected transgenic corn (Bt-corn) was based on the expression of Cry1Ab or Cry1Fa proteins. Currently, the trend is the combination of two or more genes expressing proteins that bind to different targets. In addition to broadening the spectrum of action, this strategy helps to delay the evolution of resistance in exposed insect populations. One of such examples is the combination of Cry1A.105 with Cry1Fa and Cry2Ab to control O. nubilalis and S. frugiperda. Cry1A.105 is a chimeric protein with domains I and II and the C-terminal half of the protein from Cry1Ac, and domain III almost identical to Cry1Fa. The aim of the present study was to determine whether the chimeric Cry1A.105 has shared binding sites either with Cry1A proteins, with Cry1Fa, or with both, in O. nubilalis and in S. frugiperda. Brush-border membrane vesicles (BBMV) from last instar larval midguts were used in competition binding assays with 125I-labeled Cry1A.105, Cry1Ab, and Cry1Fa, and unlabeled Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac, Cry1Fa, Cry2Ab and Cry2Ae. The results showed that Cry1A.105, Cry1Ab, Cry1Ac and Cry1Fa competed with high affinity for the same binding sites in both insect species. However, Cry2Ab and Cry2Ae did not compete for the binding sites of Cry1 proteins. Therefore, according to our results, the development of cross-resistance among Cry1Ab/Ac, Cry1A.105, and Cry1Fa proteins is possible in these two insect species if the alteration of shared binding sites occurs. Conversely, cross-resistance between these proteins and Cry2A proteins is very unlikely in such case

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology