The emergence and increasing prevalence of multidrug-resistant bacterial pathogens emphasizes the need for new and innovative antimicrobial strategies. Lytic phages, which kill their host following amplification and release of progeny phage into the environment, may offer an alternative strategy for combating bacterial infections. In this study, however, we describe the use of a nonlytic phage to specifically target and deliver DNA encoding bactericidal proteins to bacteria. To test the concept of using phage as a lethal-agent delivery vehicle, we used the M13 phagemid system and the addiction toxins Gef and ChpBK. Phage delivery of lethal-agent phagemids reduced target bacterial numbers by several orders of magnitude in vitro and in a bacteremic mouse model of infection. Given the powerful genetic engineering tools available and the present knowledge in phage biology, this technology may have potential use in antimicrobial therapies and DNA vaccine development.

We discuss a parameter-free and computationally efficient ab initio simulation approach for moderately and strongly correlated materials, the multitier self-consistent GW +EDMFT method. This scheme treats different degrees of freedom, such as high-energy and low-energy bands, or local and nonlocal interactions, within appropriate levels of approximation, and provides a fully self-consistent description of correlation and screening effects in the solid. The ab initio input is provided by a one-shot G 0 W 0 calculation, while the strong-correlation effects originating from narrow bands near the Fermi level are captured by a combined GW plus extended dynamical mean-field (EDMFT) treatment. We present the formalism and technical details of our implementation and discuss some general properties of the effective EDMFT impurity action. In particular, we show that the retarded impurity interactions can have non-causal features, while the physical observables, such as the screened interactions of the lattice system, remain causal. As a first application, we present ab initio simulation results for SrMoO3, which demonstrate the existence of prominent plasmon satellites in the spectral function not obtainable within LDA+DMFT, and provide further support for our recent re-interpretation of the satellite features in the related cubic perovskite SrVO3. We then turn to stretched sodium as a model system to explore the performance of the multitier self-consistent GW +EDMFT method in situations with different degrees of correlation. While the results for the physical lattice spacing a0 show that the scheme is not very accurate for electron-gas like systems, because nonlocal corrections beyond GW are important, it does provide physically correct results in the intermediate correlation regime, and a Mott transition around a lattice spacing of 1.5a0. Remarkably, even though the Wannier functions in the stretched compound are less localized, and hence the bare interaction parameters are reduced, the self-consistently computed impurity interactions show the physically expected trend of an increasing interaction strength with increasing lattice spacing.

Topologically nontrivial two-dimensional materials hold great promise for next-generation optoelectronic applications. However, measuring the Hall or spin-Hall response is often a challenge and practically limited to the ground state. An experimental technique for tracing the topological character in a differential fashion would provide useful insights. In this work, we show that circular dichroism angle-resolved photoelectron spectroscopy (ARPES) provides a powerful tool which can resolve the topological and quantum-geometrical character in momentum space. In particular, we investigate how to map out the signatures of the local Berry curvature by exploiting its intimate connection to the orbital angular momentum. A spin-resolved detection of the photoelectrons allows to extend the approach to spin-Chern insulators. Our predictions are corroborated by state-of-the art ab initio simulations employing time-dependent density functional theory, complemented with model calculations. The present proposal can be extended to address topological properties in materials out of equilibrium in a time-resolved fashion.

The nares represent an important bacterial reservoir for endogenous infections. This study aimed to assess the prevalence of nasal colonization by different important pathogens, the associated antimicrobial susceptibility and risk factors. We performed a prospective cohort study among 1878 nonhospitalized volunteers recruited from the general population in Germany. Participants provided nasal swabs at three time points (each separated by 4–6 months). Staphylococcus aureus, Enterobacteriaceae and important nonfermenters were cultured and subjected to susceptibility testing. Factors potentially influencing bacterial colonization patterns were assessed. The overall prevalence of S. aureus, Enterobacteriaceae and nonfermenters was 41.0, 33.4 and 3.7%, respectively. Thirteen participants (0.7%) were colonized with methicillin-resistant S. aureus. Enterobacteriaceae were mostly (>99%) susceptible against ciprofloxacin and carbapenems (100%). Extended-spectrum β-lactamase–producing isolates were not detected among Klebsiella oxytoca, Klebsiella pneumoniae and Escherichia coli. Several lifestyle- and health-related factors (e.g. household size, travel, livestock density of the residential area or occupational livestock contact, atopic dermatitis, antidepressant or anti-infective drugs) were associated with colonization by different microorganisms. This study unexpectedly demonstrated high nasal colonization rates with Enterobacteriaceae in the German general population, but rates of antibiotic resistance were low. Methicillin-resistant S. aureus carriage was rare but highly associated with occupational livestock contact.

We investigated the hypothesis that salivary gland inoculation stimulates formation of ectopic germinal centers (GCs), transforming the gland into a mucosal inductive site. Intraglandular infection of mice with murine cytomegalovirus (MCMV; control: UV-inactivated MCMV) induces salivary gland ectopic follicles comprising cognate interactions between CD4(+) and B220(+) lymphocytes, IgM(+) and isotype-switched IgG(+) and IgA(+) B cells, antigen presenting cells, and follicular dendritic cells. B cells coexpressed the GC markers GCT (57%) and GL7 (52%), and bound the lectin peanut agglutinin. Lymphoid follicles were characterized by a 2- to 3-fold increase in mRNA for CXCL13 (lymphoid neogenesis), syndecan-1 (plasma cells), Blimp-1 (plasma cell development/differentiation), and a 2- to 6-fold increase for activation-induced cytidine deaminase, PAX5, and the nonexcised rearranged DNA of an IgA class-switch event, supporting somatic hypermutation and class-switch recombination within the salivary follicles. Intraglandular inoculation also provided protection against a systemic MCMV challenge, as evidenced by decreased viral titers (10(5) plaque-forming units to undetectable), and restoration of normal salivary flow rates from a 6-fold decrease. Therefore, these features suggest that the salivary gland participates in oral mucosal immunity via generation of ectopic GCs, which function as ectopic mucosal inductive sites.