In vitro and in vivo screening for novel essential cell-envelope proteins in Pseudomonas aeruginosa

The Gram-negative bacterium Pseudomonas aeruginosa represents a prototype of multi-drug resistant opportunistic pathogens for which novel therapeutic options are urgently required. In order to identify new candidates as potential drug targets, we combined large-scale transposon mutagenesis data analysis and bioinformatics predictions to retrieve a set of putative essential genes which are conserved in P. aeruginosa and predicted to encode cell envelope or secreted proteins. By generating unmarked deletion or conditional mutants, we confirmed the in vitro essentiality of two periplasmic proteins, LptH and LolA, responsible for lipopolysaccharide and lipoproteins transport to the outer membrane respectively, and confirmed that they are important for cell envelope stability. LptH was also found to be essential for P. aeruginosa ability to cause infection in different animal models. Conversely, LolA-depleted cells appeared only partially impaired in pathogenicity, indicating that this protein likely plays a less relevant role during bacterial infection. Finally, we ruled out any involvement of the other six proteins under investigation in P. aeruginosa growth, cell envelope stability and virulence. Besides proposing LptH as a very promising drug target in P. aeruginosa, this study confirms the importance of in vitro and in vivo validation of potential essential genes identified through random transposon mutagenesis

The very forward CASTOR calorimeter of the CMS experiment

International audienceThe physics motivation, detector design, triggers, calibration, alignment, simulation, and overall performance of the very forward CASTOR calorimeter of the CMS experiment are reviewed. The CASTOR Cherenkov sampling calorimeter is located very close to the LHC beam line, at a radial distance of about 1 cm from the beam pipe, and at 14.4 m from the CMS interaction point, covering the pseudorapidity range of $-$6.6 $\lt\eta\lt$ $-$5.2. It was designed to withstand high ambient radiation and strong magnetic fields. The performance of the detector in measurements of forward energy density, jets, and processes characterized by rapidity gaps, is reviewed using data collected in proton and nuclear collisions at the LHC

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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