Role of the Outer Membrane and Porins in Susceptibility of β -Lactamase-Producing Enterobacteriaceae to Ceftazidime-Avibactam

International audienceThis study examined the activity of the novel antimicrobial combination ceftazidime-avibactam against Enterobacteriaceae exhibiting different outer membrane permeability profiles, specifically with or without porins and with or without expression of the main efflux pump (AcrAB-TolC). The addition of the outer membrane permeabilizer polymyxin B nonapeptide increased the antibacterial activities of avibactam alone, ceftazidime alone, and ceftazidime-avibactam against the characterized clinical isolates of Escherichia coli, Enterobacter aerogenes, and Klebsiella pneumoniae. This enhancement of activities was mainly due to increased passive penetration of compounds since inhibition of efflux by the addition of phenylalanine-arginine-naphthylam-ide affected the MICs minimally. OmpF (OmpK35) or OmpC (OmpK36) pores were not the major route by which avibactam crossed the outer membranes of E. coli and K. pneumoniae. In contrast, Omp35 and Omp36 allowed diffusion of avibactam across the outer membrane of E. aerogenes, although other diffusion channels for avibactam were also present in that species. It was clear that outer membrane permeability and outer membrane pore-forming proteins play a key role in the activity of ceftazi-dime-avibactam. Nevertheless, the MICs of ceftazidime-avibactam (with 4 mg/liter avibactam) against the ceftazidime-resistant clinical isolates of the three species of Enterobacteriaceae studied were <8 mg/liter, regardless of outer membrane permeability changes resulting from an absence of defined porin proteins or upregulation of efflux

Cytosolic and Secreted Peptidoglycan-Degrading Enzymes in Drosophila Respectively Control Local and Systemic Immune Responses to Microbiota

International audienc

Crystal structure and biochemical characterization of the transmembrane PAP2 type phosphatidylglycerol phosphate phosphatase from Bacillus subtilis.

Type 2 phosphatidic acid phosphatases (PAP2s) can be either soluble or integral membrane enzymes. In bacteria, integral membrane PAP2s play major roles in the metabolisms of glycerophospholipids, undecaprenyl-phosphate (C55-P) lipid carrier and lipopolysaccharides. By in vivo functional experiments and biochemical characterization we show that the membrane PAP2 coded by the Bacillus subtilis yodM gene is the principal phosphatidylglycerol phosphate (PGP) phosphatase of B. subtilis. We also confirm that this enzyme, renamed bsPgpB, has a weaker activity on C55-PP. Moreover, we solved the crystal structure of bsPgpB at 2.25 A resolution, with tungstate (a phosphate analog) in the active site. The structure reveals two lipid chains in the active site vicinity, allowing for PGP substrate modeling and molecular dynamic simulation. Site-directed mutagenesis confirmed the residues important for substrate specificity, providing a basis for predicting the lipids preferentially dephosphorylated by membrane PAP2s

Les Parisiennes : des femmes dans la ville (Moyen Âge - XVIIIe siècle)

Géographes et sociologues s’accordent pour penser que la ville du XXe siècle a été faite par et pour les hommes. Si les études de genre permettent d’interroger les pratiques et les politiques de la ville aujourd’hui, que peut nous apprendre l’histoire sur la place, l’activité et les représentations des femmes dans les centres urbains ? En faisant converger différents regards (histoire sociale, économique, religieuse et culturelle, histoire du droit et des institutions, études littéraires), les analyses de ce volume contribuent à rendre visibles la présence et les actions des femmes, des plus humbles aux plus célèbres, et les mettent en perspective avec leurs représentations. Paris, en tant que centre urbain majeur et creuset privilégié des modèles sociaux et culturels français, apparaît comme un lieu à la fois exemplaire et singulier pour construire ce savoir. En parcourant les rues de la capitale, en entrant dans ses couvents comme dans ses prisons, en visitant ses salons et ses théâtres, ses lieux de promenade aussi bien que ses lieux de commerce, lectrices et lecteurs verront se dessiner des rapports de genre parfois inattendus, que subissent ou qu’exploitent les Parisiennes