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Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches.

Wheat germin is a homopentameric 125 kD glycoprotein mainly localized in the cell wall of monocots, and is a specific marker of the onset of growth in germinating seeds. The major objective of this study was to examine the expression and oxalate oxidase activity of two wheat germin isoforms: gf-2.8 and gf-3.8 in transgenic tobacco plants. The transgenic tobacco plants were created with different constructs: 1) one entire excision of gf-2.8 germin promoter and two partially deleted promoter sequences were used to generate 3 independent GUS constructs; 2) the whole gf-2.8 gene construct and the fusion with CaMV 35S promoter; 3) one entire excision of gf-3.8 germin gene and one partially deleted gf-3.8 promoter sequences were used to generate 2 independent GUS constructs; 4) the whole gf-3.8 gene and the fusion with CaMV 35S promoter. Hormonal treatment (auxin and gibberellin), salt treatment, heavy metals (Mn, Fe, Co, Ni, Cu, Zn, Cd, Hg, As) and Al induced high GUS activity in tobacco transformed with entire and one partially deleted of the gf-2.8 gene. The immunoblotting confirmed induction of gf-2.8 gene and its product expressed oxalate oxidase activity in tobacco transformed with the entire gf-2.8 construct. Neither nicotinic acid, salicylic acid, heat shock, cold nor UV-C have enhanced significant GUS activity and germin gf-2.8 synhesis and activity.

[Abstract] One of the most compelling approaches in the discovery of novel antimicrobials is screening of natural sources. In our publication we report on the activity of a compound 8hydroxyserrulat-14-en-19-oic acid (EN4), a diterpene isolated from the Australian plant Eremophila neglecta. We evaluate its applicability for treatment of implant-associated infections. A comprehensive analysis of the mechanism of action of EN4 against Staphylococci revealed its membranolytic properties and a general inhibition of macromolecular biosynthesis, which was confirmed in a macromolecular biosynthesis assay and suggested a multitarget activity. The method used to investigate an influence of EN4 on the synthesis of peptidoglycan, RNA, DNA and proteins is based on precipitation of macromolecules with trichloroacetic acid. These macromolecules are synthesised from respective [ 3 H]-labelled precursors. The incorporated radioactivity with and without an antimicrobial is measured and it reflects the mode of action of the tested compound. Antibiotics with known mechanisms of action are used as controls.

Treatment options are limited for implant-associated infections (IAI) that are mainly caused by biofilm-forming staphylococci. We report here on the activity of the serrulatane compound 8-hydroxyserrulat-14-en-19-oic acid (EN4), a diterpene isolated from the Australian plant Eremophila neglecta . EN4 elicited antimicrobial activity toward various Gram-positive bacteria but not to Gram-negative bacteria. It showed a similar bactericidal effect against logarithmic-phase, stationary-phase, and adherent Staphylococcus epidermidis , as well as against methicillin-susceptible and methicillin-resistant S. aureus with MICs of 25 to 50 μg/ml and MBCs of 50 to 100 μg/ml. The bactericidal activity of EN4 was similar against S. epidermidis and its Δ ica mutant, which is unable to produce polysaccharide intercellular adhesin-mediated biofilm. In time-kill studies, EN4 exhibited a rapid and concentration-dependent killing of staphylococci, reducing bacterial counts by >3 log 10 CFU/ml within 5 min at concentrations of >50 μg/ml. Investigation of the mode of action of EN4 revealed membranolytic properties and a general inhibition of macromolecular biosynthesis, suggesting a multitarget activity. In vitro -tested cytotoxicity on eukaryotic cells was time and concentration dependent in the range of the MBCs. EN4 was then tested in a mouse tissue cage model, where it showed neither bactericidal nor cytotoxic effects, indicating an inhibition of its activity. Inhibition assays revealed that this was caused by interactions with albumin. Overall, these findings suggest that, upon structural changes, EN4 might be a promising pharmacophore for the development of new antimicrobials to treat IAI.

Thin polymer films that prevent the adhesion of bacteria are of interest as coatings for the development of infection-resistant biomaterials. This study investigates the influence of grafting density and film thickness on the adhesion of Staphylococcus epidermidis to poly(poly(ethylene glycol) methacrylate) (PPEGMA) and poly(2-hydroxyethyl methacrylate) (PHEMA) brushes prepared via surface-initiated atom transfer radical polymerization (SI-ATRP). These brushes are compared with poly(ethylene glycol) (PEG) brushes, which are obtained by grafting PEG onto an epoxide-modified substrate. Except for very low grafting densities (rho = 1%), crystal violet staining experiments show that the PHEMA and PPEGMA brushes are equally effective as the PEG-modified surfaces in preventing S. epidermis adhesion and do not reveal any significant variations as a function of film thickness or grafting density. These results indicate that brushes generated by SI-ATRP are an attractive alternative to grafted-onto PEG films for the preparation of surface coatings that resist bacterial adhesion.