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

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)

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

The pseudogap behavior in the stoichiometric FeSe superconductor (Tc~9.4 K)

This paper reports the synthesis and superconducting behaviors of the tetragonal iron-chalcogenide superconductor FeSe. The electrical resistivity and magnetic moment measurements confirmed its superconductivity with a $T_c^{zero}$ and $T_c^{mag}$ at 9.4 K under ambient pressure. EPMA indicated the sample to have a stoichiometric Fe:Se ratio of 1:1 ($\pm$0.02). The Seebeck coefficient which was 12.3 $\mu$V/K at room temperature, changed to a negative value near 200 K, indicating it to be a two carriers material. Above $T_c$, the $\rho(T)$ curve revealed an 'S' shape. Hence $d\rho(T)/dT$, and $d^2\rho(T)/dT^2$ showed pseudogap-like behavior at $T^*$=110 K according to the resistivity curvature mapping (RCM) method for high $T_c$ cuprates. Moreover, the magnetoresistance $\rho_H(T)/\rho_{H=0}$ under a magnetic field and the Seebeck coefficient $S(T)$ revealed revealed pseudogap-like behavior near $T^*$. Interestingly, at the same temperature, 30 K, the sign of $S(T)$ and all signs of $d^2\rho(T)/dT^2$ changed from negative to positive above $T_c$.Comment: 10 pages, 6 figure

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

One-dimensional hexagonal boron nitride conducting channel

Hexagonal boron nitride (hBN) is an insulating two-dimensional (2D) material with a large bandgap. Although known for its interfacing with other 2D materials and structural similarities to graphene, the potential use of hBN in 2D electronics is limited by its insulating nature. Here, we report atomically sharp twin boundaries at AA???/AB stacking boundaries in chemical vapor deposition???synthesized few-layer hBN. We find that the twin boundary is composed of a 6???6??? configuration, showing conducting feature with a zero bandgap. Furthermore, the formation mechanism of the atomically sharp twin boundaries is suggested by an analogy with stacking combinations of AA???/AB based on the observations of extended Klein edges at the layer boundaries of ABstacked hBN. The atomically sharp AA???/AB stacking boundary is promising as an ultimate 1D electron channel embedded in insulating pristine hBN. This study will provide insights into the fabrication of single-hBN electronic devices

Antibiotic resistance mechanisms inform discovery: identification and characterization of a novel amycolatopsis strain producing ristocetin.

Discovering new antibiotics is a major scientific challenge, made increasingly urgent by the continued development of resistance in bacterial pathogens. A fundamental understanding of the mechanisms of bacterial antibiotic resistance will be vital for the future discovery or design of new, more effective antibiotics. We have exploited our intimate knowledge of the molecular mechanism of glycopeptide antibiotic resistance in the harmless bacterium Streptomyces coelicolor to develop a new two-step cell wall bioactivity screen, which efficiently identified a new actinomycete strain containing a previously uncharacterized glycopeptide biosynthetic gene cluster. The screen first identifies natural product extracts capable of triggering a generalized cell wall stress response and then specifically selects for glycopeptide antibacterials by assaying for the induction of glycopeptide resistance genes. In this study, we established a diverse natural product extract library from actinomycete strains isolated from locations with widely varying climates and ecologies, and we screened them using the novel two-step bioassay system. The bioassay ultimately identified a single strain harboring the previously unidentified biosynthetic gene cluster for the glycopeptide ristocetin, providing a proof of principle for the effectiveness of the screen. This is the first report of the ristocetin biosynthetic gene cluster, which is predicted to include some interesting and previously uncharacterized enzymes. By focusing on screening libraries of microbial extracts, this strategy provides the certainty that identified producer strains are competent for growth and biosynthesis of the detected glycopeptide under laboratory conditions.This work was supported by funding from the Royal Society, UK (516002.K5877/ROG), the Medical Research council, UK (G0700141) and St. John’s College, University of CambridgeThis the the author accepted manuscript. The final version is available from ASM at http://aac.asm.org/content/early/2014/07/09/AAC.03349-14.abstract