Draft Genome Sequence of Amycolatopsis lurida NRRL 2430, Producer of the Glycopeptide Family Antibiotic Ristocetin.

We report here the first draft genome sequence for Amycolatopsis lurida NRRL 2430, the producer of the glycopeptide antibiotic ristocetin. The 9-Mbp genome is predicted to harbor 8,143 genes, including those belonging to the ristocetin biosynthesis cluster and 31 additional predicted secondary metabolite gene clusters.This work was supported by the grants from the Royal Society (516002.K5877/ROG) and the Medical Research Council (G0700141).This paper was originally published in Genome Announcements (Kwun MJ, Hong H-J, Genome Announcements 2014, 2(5):e01050-14. doi:10.1128/genomeA.01050-14)

The activity of glycopeptide antibiotics against resistant bacteria correlates with their ability to induce the resistance system.

Glycopeptide antibiotics containing a hydrophobic substituent display the best activity against vancomycin-resistant enterococci, and they have been assumed to be poor inducers of the resistance system. Using a panel of 26 glycopeptide derivatives and the model resistance system in Streptomyces coelicolor, we confirmed this hypothesis at the level of transcription. Identification of the structural glycopeptide features associated with inducing the expression of resistance genes has important implications in the search for more effective antibiotic structures.This work was supported by the Royal Society (516002.K5877/ROG) and the Medical Research Council (G0700141).This is the accepted manuscript version. The final version is available from ASM at http://aac.asm.org/content/early/2014/07/30/AAC.03668-14.abstract

Genome Sequence of Streptomyces toyocaensis NRRL 15009, Producer of the Glycopeptide Antibiotic A47934.

Here we report the draft genome sequence of Streptomyces toyocaensis strain NRRL 15009 which is the producer of the glycopeptide antibiotic A47934. The genome sequence is predicted to harbor a total of 26 secondary metabolite biosynthetic gene clusters including the A47934 cluster.This work was supported by grants from the Royal Society (516002.K5877/ ROG) and the Medical Research Council (G0700141).This is the final published version, also available from ASM at http://genomea.asm.org/content/2/4/e00749-14

Postnatal β-catenin deletion from Dmp1-expressing osteocytes/osteoblasts reduces structural adaptation to loading, but not periosteal load-induced bone formation

Mechanical signal transduction in bone tissue begins with load-induced activation of several cellular pathways in the osteocyte population. A key pathway that participates in mechanotransduction is Wnt/Lrp5 signaling. A putative downstream mediator of activated Lrp5 is the nucleocytoplasmic shuttling protein β-catenin (βcat), which migrates to the nucleus where it functions as a transcriptional co-activator. We investigated whether osteocytic βcat participates in Wnt/Lrp5-mediated mechanotransduction by conducting ulnar loading experiments in mice with or without chemically induced βcat deletion in osteocytes. Mice harboring βcat floxed loss-of-function alleles (βcat(f/f)) were bred to the inducible osteocyte Cre transgenic (10)(kb)Dmp1-CreERt2. Adult male mice were induced to recombine the βcat alleles using tamoxifen, and intermittent ulnar loading sessions were applied over the following week. Although adult-onset deletion of βcat from Dmp1-expressing cells reduced skeletal mass, the bone tissue was responsive to mechanical stimulation as indicated by increased relative periosteal bone formation rates in recombined mice. However, load-induced improvements in cross sectional geometric properties were compromised in recombined mice. The collective results indicate that the osteoanabolic response to loading can occur on the periosteal surface when β-cat levels are significantly reduced in Dmp1-expressing cells, suggesting that either (i) only low levels of β-cat are required for mechanically induced bone formation on the periosteal surface, or (ii) other additional downstream mediators of Lrp5 might participate in transducing load-induced Wnt signaling

Explaining Physicians’ Acceptance and Resistance to the NHI Pharmacloud: A Theoretical Model and Empirical Test

The PharmaCloud allows physicians to streamline many of their healthcare processes and ensure patient safety in a more efficient and cost-effective manner. Despite its great potential, however, there are gaps in our understanding of how physicians evaluate change in relation to the PharmaCloud and why they decide to resist it. Thus, this study develops an integrated model to explain physicians’ intention to use the PharmaCloud and their intention to resist it. A field survey was conducted in Taiwan to collect data from physicians. Structural equation modeling (SEM) using the partial least squares (PLS) method was employed to test the research model. The results show that physicians’ resistance to the use of the PharmaCloud is the result of regret avoidance, inertia, perceived value, transition costs, and perceived threat. Information quality, system quality, and service quality are shown to have positive and direct effects on physicians’ intention to use the PharmaCloud. Our study illustrates the importance of incorporating user resistance in technology acceptance studies in general and health technology usage studies in particular, providing grounds for a model of resistance that can serve as the starting point for future research in this relatively unexplored yet potentially fertile area of research

In Vivo Characterization of the Activation and Interaction of the VanR-VanS Two-Component Regulatory System Controlling Glycopeptide Antibiotic Resistance in Two Related Streptomyces Species.

This is the author accepted manuscript. The final version is available from the American Society for Microbiology via http://dx.doi.org/10.1128/AAC.01367-15The VanR-VanS two-component system is responsible for inducing resistance to glycopeptide antibiotics in various bacteria. We have performed a comparative study of the VanR-VanS systems from two streptomyces strains, Streptomyces coelicolor and Streptomyces toyocaensis, to characterize how the two proteins cooperate to signal the presence of antibiotics and to define the functional nature of each protein in each strain background. The results indicate that the glycopeptide antibiotic inducer specificity is determined solely by the differences between the amino acid sequences of the VanR-VanS two-component systems present in each strain rather than by any inherent differences in general cell properties, including cell wall structure and biosynthesis. VanR of S. coelicolor (VanRsc) functioned with either sensor kinase partner, while VanR of S. toyocaensis (VanRst) functioned only with its cognate partner, S. toyocaensis VanS (VanSst). In contrast to VanRsc, which is known to be capable of phosphorylation by acetylphosphate, VanRst could not be activated in vivo independently of a VanS sensor kinase. A series of amino acid sequence modifications changing residues in the N-terminal receiver (REC) domain of VanRst to the corresponding residues present in VanRsc failed to create a protein capable of being activated by VanS of S. coelicolor (VanSsc), which suggests that interaction of the response regulator with its cognate sensor kinase may require a region more extended than the REC domain. A T69S amino acid substitution in the REC domain of VanRst produced a strain exhibiting weak constitutive resistance, indicating that this particular amino acid may play a key role for VanS-independent phosphorylation in the response regulator protein.This work was supported by funding from the Medical Research Council, UK (G0700141) and the Royal Society, UK (516002.K5877/ROG). the American Society for Microbiology

Hypersensitive Reaction to Praziquantel in a Clonorchiasis Patient

Praziquantel is the drug of choice for clonorchiasis. Since clonorchiasis is endemic in most river basins, praziquantel has been widely used for 30 years in Korea. A 54-year-old Korean woman suffered from hypersensitive reactions, such as nausea, dyspnea, rash, and urticaria after taking the first dose of praziquantel to treat clonorchiasis. She ingested one dose again and the same symptoms appeared, and she was treated at a clinic with anti-histamines. She tried one more dose with anti-histamines but found the same symptoms. Later, she was found to pass eggs of Clonorchis sinensis and medicated with flubendazole. The hypersensitive reaction to praziquantel is rare but occurs. This is the 5th case report in the world