Daptomycin Resistant Staphylococcus aureus Clinical Strain With Novel Non-synonymous Mutations in the mprF and vraS Genes:A New Insight Into Daptomycin Resistance

Objectives: Daptomycin (DAP) resistance in Staphylococcus aureus is uncommon but there are increasing reports of the emergence of resistance during DAP therapy. Most clinical DAP-resistant S. aureus isolates investigated carried mutations in the mprF gene. The aim of this study was to identify mutations between a clinical pair of methicillin-susceptible S. aureus (MSSA) isolates (DAP-susceptible and DAP-resistant). Additionally, the activity of genes previously associated with DAP resistance was assessed. Materials and Methods: Two MSSA isolates from patient with left-sided endocarditis were analyzed by whole genome sequencing (WGS) and reverse transcription-quantitative real-time PCR (RT-qPCR). The first isolate, DAP-susceptible, was obtained before initiation of treatment and the second isolate, DAP-resistant, was recovered after 4 weeks of DAP therapy. Results: Comparison of complete genomes of DAP-susceptible and its DAP-resistant variant identified two non-synonymous and one synonymous mutations. The non-synonymous mutations consisted of a S829L substitution in mprF and a T331I substitution in vraS. The RT-qPCR experiments revealed an increased expression of vraS, dltA, mprF, and sceD genes in DAP-resistant variant. Strikingly, the expression of dltA and mprF genes was significantly downregulated by DAP. Conclusion: The mprF and vraS genes were previously associated with DAP resistance, however, none of the mutations described in this study had been previously identified and linked to DAP resistance. Moreover, we provide a new insight into the DAP action on S. aureus, in which the expression of key genes in DAP resistance is decreased by the antibiotic

Kinematically complete experimental study of Compton scattering at helium atoms near the ionization threshold

Compton scattering is one of the fundamental interaction processes of light with matter. Already upon its discovery [1] it was described as a billiard-type collision of a photon kicking a quasi-free electron. With decreasing photon energy, the maximum possible momentum transfer becomes so small that the corresponding energy falls below the binding energy of the electron. Then ionization by Compton scattering becomes an intriguing quantum phenomenon. Here we report a kinematically complete experiment on Compton scattering at helium atoms below that threshold. We determine the momentum correlations of the electron, the recoiling ion, and the scattered photon in a coincidence experiment finding that electrons are not only emitted in the direction of the momentum transfer, but that there is a second peak of ejection to the backward direction. This finding links Compton scattering to processes as ionization by ultrashort optical pulses [2], electron impact ionization [3,4], ion impact ionization [5,6], and neutron scattering [7] where similar momentum patterns occur.Comment: 7 pages, 4 figure

Comparison of circulating tumor cells and AR-V7 as clinical biomarker in metastatic castration-resistant prostate cancer patients

Abstract Biomarker in metastatic castration resistant prostate cancer (mCRPC) treatment are rare. We aimed to compare the clinical value of circulating tumor cells (CTCs) and androgen receptor splice variant 7 (AR-V7) as biomarker in mCRPC patients undergoing androgen receptor-targeted agent (ARTA) treatment. Overall cohort (65 patients) was stratified regarding either CTC or AR-V7 status followed by further sub-stratification of the respective other marker. Subsequently, prostate specific antigen (PSA) response, progression free survival (PFS) and overall survival (OS)) of subgroups was compared. CTCs and AR-V7 were detected in 54 (83%) and 33 (61%) patients, respectively. All AR-V7 + were CTC +. We detected PSA response in all subgroups. For PFS and OS, biomarker stratification revealed differences between all subgroups. Interestingly, no significant differences of AR-V7 transcript copy numbers were detected between responding and non-responding patients. Additionally, multivariable analysis revealed no independent prognostic value of AR-V7 positivity. Both biomarkers show clinical value in prognosticating clinical outcome. Nonetheless, AR-V7 stratification underestimates the heterogenous subgroup of CTC − and CTC + patient, the latter requiring more intense clinical surveillance. Additionally, AR-V7 level does not correlate with clinical response. Thus, the value of AR-V7 as a clinical biomarker must be considered skeptically

Geographic Distribution of Staphylococcus aureus Causing Invasive Infections in Europe: A Molecular-Epidemiological Analysis

Hajo Grundmann and colleagues describe the development of a new interactive mapping tool for analyzing the spatial distribution of invasive Staphylococcus aureus clones

Integrated chromosomal and plasmid sequence analyses reveal diverse modes of carbapenemase gene spread among Klebsiella pneumoniae.

Molecular and genomic surveillance systems for bacterial pathogens currently rely on tracking clonally evolving lineages. By contrast, plasmids are usually excluded or analyzed with low-resolution techniques, despite being the primary vectors of antibiotic resistance genes across many key pathogens. Here, we used a combination of long- and short-read sequence data of Klebsiella pneumoniae isolates (n = 1,717) from a European survey to perform an integrated, continent-wide study of chromosomal and plasmid diversity. This revealed three contrasting modes of dissemination used by carbapenemase genes, which confer resistance to last-line carbapenems. First, blaOXA-48-like genes have spread primarily via the single epidemic pOXA-48-like plasmid, which emerged recently in clinical settings and spread rapidly to numerous lineages. Second, blaVIM and blaNDM genes have spread via transient associations of many diverse plasmids with numerous lineages. Third, blaKPC genes have transmitted predominantly by stable association with one successful clonal lineage (ST258/512) yet have been mobilized among diverse plasmids within this lineage. We show that these plasmids, which include pKpQIL-like and IncX3 plasmids, have a long association (and are coevolving) with the lineage, although frequent recombination and rearrangement events between them have led to a complex array of mosaic plasmids carrying blaKPC Taken altogether, these results reveal the diverse trajectories of antibiotic resistance genes in clinical settings, summarized as using one plasmid/multiple lineages, multiple plasmids/multiple lineages, and multiple plasmids/one lineage. Our study provides a framework for the much needed incorporation of plasmid data into genomic surveillance systems, an essential step toward a more comprehensive understanding of resistance spread

The dynamic changes of dominant clones of Staphylococcus aureus causing bloodstream infections in the European region : Results of a second structured survey

Staphylococcus aureus is one of the most important human pathogens and meticillin-resistant S. aureus (MRSA) presents a major cause of healthcare- and community-acquired infections. This study investigated the spatial and temporal changes of S. aureus causing bacteraemia in Europe over a five-year interval and explored the possibility of integrating pathogen-based typing data with epidemiological and clinical information at a European level. Between January 2011 and July 2011, 350 laboratories serving 453 hospitals in 25 countries collected 3,753 isolates (meticillin-sensitive S. aureus (MSSA) and MRSA) from patients with S. aureus bloodstream infections. All isolates were sent to the national staphylococcal reference laboratories and characterised by quality-controlled spa typing. Data were uploaded to an interactive web-based mapping tool. A wide geographical distribution of spa types was found, with some prevalent in all European countries. MSSA was more diverse than MRSA. MRSA differed considerably between countries with major international clones expanding or receding when compared to a 2006 survey. We provide evidence that a network approach of decentralised typing and visualisation of aggregated data using an interactive mapping tool can provide important information on the dynamics of S. aureus populations such as early signalling of emerging strains, cross-border spread and importation by travel.Peer reviewe

Escherichia coli and Staphylococcus aureus: bad news and good news from the European Antimicrobial Resistance Surveillance Network (EARS-Net), formerly EARSS), 2002 to 2009

Based on data collected by the European Antimicrobial Resistance Surveillance Network (EARS-Net) and the former EARSS, the present study describes the trends in antimicrobial susceptibility patterns and occurrence of invasive infections caused by Escherichia coli and Staphylococcus aureus in the period from 2002 to 2009. Antimicrobial susceptibility results from 198 laboratories in 22 European countries reporting continuously on these two microorganisms during the entire study period were included in the analysis. The number of bloodstream infections caused by E. coli increased remarkably by 71% during the study period, while bloodstream infections caused by S. aureus increased by 34%. At the same time, an alarming increase of antimicrobial resistance in E. coli was observed, whereas for S. aureus the proportion of meticillin resistant isolates decreased. The observed trend suggests an increasing burden of disease caused by E. coli. The reduction in the proportion of meticillin-resistant S. aureus and the lesser increase in S. aureus infections, compared with E. coli, may reflect the success of infection control measures at hospital level in several European countries.</p

High Power Electric Propulsion: MARS plus EUROPA – Already Beyond 2025!

It’s mid-term realization plus global strategic investments: the results of the European Russian DEMOCRITOS project (Horizon 2020) related to the MW class INPPS (International Nuclear Power and Propulsion System) flagship will be described. INPPS flagship includes high power electric thrusters cluster, supplied electric power by the nuclear reactor (successfully tested in Russia) and a solar power ring. Two INPPS versions were studied – the wide and arrow wing versions. Both versions have a futuristic design with standardized interfaces for several flagship subsystems. Especially the high payload mass of INPPS allows the transport of – for example – up to 12 t to JUPITER moon EUROPA and about 18 t to MARS – as a function of specific impulse of electric thrusters. INPPS flagship not only allows scientific, but especially commercial and communication payloads as well. This means industrial-scale production of space flight systems for robotic and human space exploration. International cooperation related to INPPS realization are necessary within an International High Power Space Transportation program to realize the DEMOCRITOS core, ground and space components until 2025. DEMOCRITOS project included partners from Europe, Russia and a Brazilian guest observer and received several inputs from NASA Cleveland and JAXA Tokyo

Mobile Asteroid Surface Scout (MASCOT) - Design, Development and Delivery of a Small Asteroid Lander Aboard Hayabusa2

MASCOT is a small asteroid lander launched on December 3rd, 2014, aboard the Japanese HAYABUSA2 asteroid sample-return mission towards the 980 m diameter C-type near-Earth asteroid (162173) 1999 JU3. MASCOT carries four full-scale asteroid science instruments and an uprighting and relocation device within a shoebox-sized 10 kg spacecraft; a complete lander comparable in mass and volume to a medium-sized science instrument on interplanetary missions. Asteroid surface science will be obtained by: MicrOmega, a hyperspectral near- to mid-infrared soil microscope provided by IAS; MASCAM, a wide-angle Si CMOS camera with multicolour LED illumination unit; MARA, a multichannel thermal infrared surface radiometer; the magnetometer, MASMAG, provided by the Technical University of Braunschweig. Further information on the conditions at or near the lander‘s surfaces is generated as a byproduct of attitude sensors and other system sensors. MASCOT uses a highly integrated, ultra-lightweight truss-frame structure made from a CFRP-foam sandwich. It has three internal mechanisms: a preload release mechanism, to release the structural preload applied for launch across the separation mechanism interface; a separation mechanism, to realize the ejection of MASCOT from the semi-recessed stowed position within HAYABUSA2; and the mobility mechanism, for uprighting and hopping. MASCOT uses semi-passive thermal control with Multi-Layer Insulation, two heatpipes and a radiator for heat rejection during operational phases, and heaters for thermal control of the battery and the main electronics during cruise. MASCOT is powered by a primary battery during its on-asteroid operational phase, but supplied by HAYABUSA2 during cruise for check-out and calibration operations as well as thermal control. All housekeeping and scientific data is transmitted to Earth via a relay link with the HAYABUSA2 main-spacecraft, also during cruise operations. The link uses redundant omnidirectional UHF-Band transceivers and patch antennae on the lander. The MASCOT On-Board Computer is a redundant system providing data storage, instrument interfacing, command and data handling, as well as autonomous surface operation functions. Knowledge of the lander’s attitude on the asteroid is key to the success of its uprighting and hopping function. The attitude is determined by a threefold set of sensors: optical distance sensors, photo electric cells and thermal sensors. A range of experimental sensors is also carried. MASCOT was build by the German Aerospace Center, DLR, with contributions from the French space agency, CNES. The system design, science instruments, and operational concept of MASCOT will be presented, with sidenotes on the development of the mission and its integration with HAYABUSA2