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The protein composition of an Outer Membrane Vesicle (OMV) preparation that constitutes the active pharmaceutical ingredient of VA-MENGOC-BC®, an effective vaccine against Neisseria meningitidis serogroups B, and C is presented. This preparation has a high lipid content and five abundant membrane proteins (FetA, PorA, PorB, RmpM, and Opc), constituting approximately 70% of the total protein mass. The protein composition was determined by combining the use of the Hexapeptide Ligand Library and an orthogonal tandem fractionation of tryptic peptides by reverse-phase chromatography at alkaline and acid pH. This approach equalizes the concentration of tryptic peptides derived from low- and high-abundance proteins as well as considerably simplifying the number of peptides analyzed by LC-MS/MS, enhancing the possibility of identifying low-abundance species. Fifty-one percent of the proteins originally annotated as membrane proteins in the genome of the MC58 strain were identified. One hundred and sixty-eight low-abundance cytosolic proteins presumably occluded within OMV were also identified. Four (NadA, NUbp, GNA2091, and fHbp), out of the five antigens constituting the Bexsero® vaccine, were detected in this OMV preparation. In particular, fHbp is also the active principle of the Trumenba® vaccine developed by Pfizer. The HpuA and HpuB gene products (not annotated in the MC58 genome) were identified in the CU385 strain, a clinical isolate that is used to produce this OMV. Considering the proteins identified here and previous work done by our group, the protein catalogue of this OMV preparation was extended to 266 different protein species.

Aim: To study the association of ABCB1 and CYP2C19 polymorphisms and the clopidogrel response in Spanish peripheral artery disease patients following percutaneous transluminal angioplasty (PTA) and to perform a meta-analysis., Materials & Methods: 72 patients were recruited and 122 patients included in the meta-analysis. We evaluated the effect of ABCB1 3435 C>T, CYP2C19*2 and CYP2C19*3 and primary end point (restenosis/occlusion of the treated lesions) during 12 months after PTA., Results: CYP2C19*2 and/or ABCB1 TT patients were associated with primary end point (OR: 5.00; 95% CI: 1.75-14.27). The meta-analysis confirmed the association of CYP2C19*2 and new atherothrombotic ischemic events (OR: 5.40; 95% CI: 2.30-12.70)., Conclusion: The CYP2C19 and ABCB1 polymorphisms could be genetic markers of cardiovascular events in peripheral artery disease patients following PTA treated with clopidogrel.

Cytotoxic proteins and prodigiosin obtained from Serratia marcescens strains are known to induce tumor cell death, nevertheless its combination has not been studied. In this paper we evaluate the combined effects of these molecules in a panel of tumor cell lines. The results showed a marked inhibitory effect on the growth of tumor cell lines derived from tumors (i.e., melanoma) which are highly resistant to conventional anticancer drugs, while normal cells were less sensitive than tumor cells. TUNEL (TdT-mediated dUTP nick end labeling) and electrophoresis of HEp-2 cell DNA treated with MG2327 preparation [containing the P50 protein belonging to the serralysins and prodigiosin, from S. marcescens CMIB4202] showed a pattern of DNA fragments typically associated with apoptosis. Interestingly, prodigiosin enhanced by 1.6-fold the cytotoxic effect of P50 when acting in combination on HEp-2 cells. The broad cytotoxic activity of the combination on tumor cells as well as its selectivity open new frontiers in cancer therapy.