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DDC: 570 × Type: article × Publisher: Amsterdam [u.a.] : Elsevier Science × WGL Institute: IPHT ×

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    Tuning the corona-core ratio of polyplex micelles for selective oligonucleotide delivery to hepatocytes or hepatic immune cells
    (Amsterdam [u.a.] : Elsevier Science, 2023) Foo, WanLing; Cseresnyés, Zoltán; Rössel, Carsten; Teng, Yingfeng; Ramoji, Anuradha; Chi, Mingzhe; Hauswald, Walter; Huschke, Sophie; Hoeppener, Stephanie; Popp, Jürgen; Schacher, Felix H.; Sierka, Marek; Figge, Marc Thilo; Press, Adrian T.; Bauer, Michael
    Targeted delivery of oligonucleotides or small molecular drugs to hepatocytes, the liver's parenchymal cells, is challenging without targeting moiety due to the highly efficient mononuclear phagocyte system (MPS) of the liver. The MPS comprises Kupffer cells and specialized sinusoidal endothelial cells, efficiently clearing nanocarriers regardless of their size and surface properties. Physiologically, this non-parenchymal shield protects hepatocytes; however, these local barriers must be overcome for drug delivery. Nanocarrier structural properties strongly influence tissue penetration, in vivo pharmacokinetics, and biodistribution profile. Here we demonstrate the in vivo biodistribution of polyplex micelles formed by polyion complexation of short interfering (si)RNA with modified poly(ethylene glycol)-block-poly(allyl glycidyl ether) (PEG-b-PAGE) diblock copolymer that carries amino moieties in the side chain. The ratio between PEG corona and siRNA complexed PAGE core of polyplex micelles was chemically varied by altering the degree of polymerization of PAGE. Applying Raman-spectroscopy and dynamic in silico modeling on the polyplex micelles, we determined the corona-core ratio (CCR) and visualized the possible micellar structure with varying CCR. The results for this model system reveal that polyplex micelles with higher CCR, i.e., better PEG coverage, exclusively accumulate and thus allow passive cell-type-specific targeting towards hepatocytes, overcoming the macrophage-rich reticuloendothelial barrier of the liver.
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    Diversity of methicillin-resistant coagulase-negative Staphylococcus spp. and methicillin-resistant Mammaliicoccus spp. isolated from ruminants and New World camelids
    (Amsterdam [u.a.] : Elsevier Science, 2021) Schauer, B.; Szostak, M.P.; Ehricht, R.; Monecke, S.; Feßler, A.T.; Schwarz, S.; Spergser, J.; Krametter-Frötscher, R.; Loncaric, I.
    Information about livestock carrying methicillin-resistant coagulase-negative staphylococci and mammaliicocci (MRCoNS/MRM) is scarce. The study was designed to gain knowledge of the prevalence, the phenotypic and genotypic antimicrobial resistance and the genetic diversity of MRCoNS/MRM originating from ruminants and New World camelids. In addition, a multi-locus sequence typing scheme for the characterization of Mammaliicoccus (formerly Staphylococcus) sciuri was developed. The study was conducted from April 2014 to January 2017 at the University Clinic for Ruminants and the Institute of Microbiology at the University of Veterinary Medicine Vienna. Seven hundred twenty-three nasal swabs originating from ruminants and New World camelids with and without clinical signs were examined. After isolation, MRCoNS/MRM were identified by MALDI-TOF, rpoB sequencing and typed by DNA microarray-based analysis and PCR. Antimicrobial susceptibility testing was conducted by agar disk diffusion. From all 723 nasal swabs, 189 MRCoNS/MRM were obtained. Members of the Mammaliicoccus (M.) sciuri group were predominant (M. sciuri (n = 130), followed by M. lentus (n = 43), M. fleurettii (n = 11)). In total, 158 out of 189 isolates showed phenotypically a multi-resistance profile. A seven-loci multi-locus sequence typing scheme for M. sciuri was developed. The scheme includes the analysis of internal segments of the house-keeping genes ack, aroE, ftsZ, glpK, gmk, pta1 and tpiA. In total, 28 different sequence types (STs) were identified among 92 selected M. sciuri isolates. ST1 was the most prevalent ST (n = 35), followed by ST 2 (n = 15), ST3 and ST5 (each n = 5), ST4 (n = 3), ST6, ST7, ST8, ST9, ST10 and ST11 (each n = 2).
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    A novel multidrug-resistant PVL-negative CC1-MRSA-IV clone emerging in Ireland and Germany likely originated in South-Eastern Europe
    (Amsterdam [u.a.] : Elsevier Science, 2019) Earls, Megan R.; Shore, Anna C.; Brennan, Gráinne I.; Simbeck, Alexandra; Schneider-Brachert, Wulf; Vremerǎ, Teodora; Dorneanu, Olivia S.; Slickers, Peter; Ehricht, Ralf; Monecke, Stefan; Coleman, David C.
    This study investigated the recent emergence of multidrug-resistant Panton-Valentine leukocidin (PVL)-negative CC1-MRSA-IV in Ireland and Germany. Ten CC1-MSSA and 139 CC1-MRSA isolates recovered in Ireland between 2004 and 2017 were investigated. These were compared to 21 German CC1-MRSA, 10 Romanian CC1-MSSA, five Romanian CC1-MRSA and two UAE CC1-MRSA, which were selected from an extensive global database, based on similar DNA microarray profiles to the Irish isolates. All isolates subsequently underwent whole-genome sequencing, core-genome single nucleotide polymorphism (cgSNP) analysis and enhanced SCCmec subtyping. Two PVL-negative clades (A and B1) were identified among four main clades. Clade A included 20 German isolates, 119 Irish isolates, and all Romanian MRSA and MSSA isolates, the latter of which differed from clade A MRSA by 47–130 cgSNPs. Eighty-six Irish clade A isolates formed a tight subclade (A1) exhibiting 0–49 pairwise cgSNPs, 80 of which harboured a 46 kb conjugative plasmid carrying both ileS2, encoding high-level mupirocin resistance, and qacA, encoding chlorhexidine resistance. The resistance genes aadE, aphA3 and sat were detected in all clade A MRSA and the majority (8/10) of clade A MSSA isolates. None of the clade A isolates harboured any enterotoxin genes other than seh, which is universally present in CC1. Clade B1 included the remaining German isolate, 17 Irish isolates and the two UAE isolates, all of which corresponded to the Western Australia MRSA-1 (WA MRSA-1) clone based on genotypic characteristics. MRSA within clades A and B1 differed by 188 cgSNPs and clade-specific SCCmec characteristics were identified, indicating independent acquisition of the SCCmec element. This study demonstrated the existence of a European PVL-negative CC1-MRSA-IV clone that is distinctly different from the well-defined PVL-negative CC1-MRSA-IV clone, WA MRSA-1. Furthermore, cgSNP analysis revealed that this newly defined clone may have originated in South-Eastern Europe, before spreading to both Ireland and Germany. © 2019 The Authors