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9,198 result(s) for "Schmidt, B."
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Persistence against benzalkonium chloride promotes rapid evolution of tolerance during periodic disinfection
Biocides used as disinfectants are important to prevent the transmission of pathogens, especially during the current antibiotic resistance crisis. This crisis is exacerbated by phenotypically tolerant persister subpopulations that can survive transient antibiotic treatment and facilitate resistance evolution. Here, we show that E. coli displays persistence against a widely used disinfectant, benzalkonium chloride (BAC). Periodic, persister-mediated failure of disinfection rapidly selects for BAC tolerance, which is associated with reduced cell surface charge and mutations in the lpxM locus, encoding an enzyme for lipid A biosynthesis. Moreover, the fitness cost incurred by BAC tolerance turns into a fitness benefit in the presence of antibiotics, suggesting a selective advantage of BAC-tolerant mutants in antibiotic environments. Our findings highlight the links between persistence to disinfectants and resistance evolution to antimicrobials. Phenotypically tolerant, persister bacterial subpopulations can survive transient antibiotic treatment and facilitate resistance evolution. Here, Nordholt et al. show that E. coli can display persistence against a widely used disinfectant and this is associated with alterations in the cell surface and with antibiotic tolerance.
GUNC: detection of chimerism and contamination in prokaryotic genomes
Genomes are critical units in microbiology, yet ascertaining quality in prokaryotic genome assemblies remains a formidable challenge. We present GUNC (the Genome UNClutterer), a tool that accurately detects and quantifies genome chimerism based on the lineage homogeneity of individual contigs using a genome’s full complement of genes. GUNC complements existing approaches by targeting previously underdetected types of contamination: we conservatively estimate that 5.7% of genomes in GenBank, 5.2% in RefSeq, and 15–30% of pre-filtered “high-quality” metagenome-assembled genomes in recent studies are undetected chimeras. GUNC provides a fast and robust tool to substantially improve prokaryotic genome quality.
Linking high harmonics from gases and solids
When intense light interacts with an atomic gas, recollision between an ionizing electron and its parent ion creates high-order harmonics of the fundamental laser frequency. This sub-cycle effect generates coherent soft X-rays and attosecond pulses, and provides a means to image molecular orbitals. Recently, high harmonics have been generated from bulk crystals, but what mechanism dominates the emission remains uncertain. To resolve this issue, we adapt measurement methods from gas-phase research to solid zinc oxide driven by mid-infrared laser fields of 0.25 volts per ångström. We find that when we alter the generation process with a second-harmonic beam, the modified harmonic spectrum bears the signature of a generalized recollision between an electron and its associated hole. In addition, we find that solid-state high harmonics are perturbed by fields so weak that they are present in conventional electronic circuits, thus opening a route to integrate electronics with attosecond and high-harmonic technology. Future experiments will permit the band structure of a solid to be tomographically reconstructed. © 2015 Macmillan Publishers Limited. All rights reserved.
Active formation of ‘chaos terrain’ over shallow subsurface water on Europa
The great lakes of Europa The Galileo spacecraft revealed a number of 'chaos' regions on Jupiter's moon Europa, where the surface terrain appears to have been disrupted from below. In many places, the surface contains sharp-edged blocks or rafts of ice that have at some point been flipped or rotated. Some characteristics of these regions have been hard to explain, such as the fact that the archetypal Conamara Chaos stands above its surroundings and contains matrix domes. Schmidt et al . apply lessons learned from analogous processes within Earth's subglacial volcanoes and ice shelves to an analysis of archival data that suggests chaos terrain forms above liquid water 'lenses' that are perched only 3 kilometres deep within the ice shell. The data suggest that ice–water interactions and freeze-out give rise to the varied morphology of chaos terrains, implying that more water is involved than has been previously appreciated — for instance, the sunken topography of Thera Macula, a large chaos area, may indicate that Europa is actively resurfacing over a lens comparable in volume to North America's Great Lakes. Europa, the innermost icy satellite of Jupiter, has a tortured young surface 1 , 2 , 3 , 4 and sustains a liquid water ocean 1 , 2 , 3 , 4 , 5 , 6 below an ice shell of highly debated thickness 1 , 2 , 3 , 4 , 5 , 7 , 8 , 9 , 10 . Quasi-circular areas of ice disruption called chaos terrains are unique to Europa, and both their formation and the ice-shell thickness depend on Europa's thermal state 1 , 2 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 . No model so far has been able to explain why features such as Conamara Chaos stand above surrounding terrain and contain matrix domes 10 , 18 . Melt-through of a thin (few-kilometre) shell 3 , 7 , 8 is thermodynamically improbable and cannot raise the ice 10 , 18 . The buoyancy of material rising as either plumes of warm, pure ice called diapirs 1 , 9 , 10 , 11 , 12 , 13 , 14 , 15 or convective cells 16 , 17 in a thick (>10 kilometres) shell is insufficient to produce the observed chaos heights, and no single plume can create matrix domes 10 , 18 . Here we report an analysis of archival data from Europa, guided by processes observed within Earth's subglacial volcanoes and ice shelves. The data suggest that chaos terrains form above liquid water lenses perched within the ice shell as shallow as 3 kilometres. Our results suggest that ice–water interactions and freeze-out give rise to the diverse morphologies and topography of chaos terrains. The sunken topography of Thera Macula indicates that Europa is actively resurfacing over a lens comparable in volume to the Great Lakes in North America.
Microbial abundance, activity and population genomic profiling with mOTUs2
Metagenomic sequencing has greatly improved our ability to profile the composition of environmental and host-associated microbial communities. However, the dependency of most methods on reference genomes, which are currently unavailable for a substantial fraction of microbial species, introduces estimation biases. We present an updated and functionally extended tool based on universal (i.e., reference-independent), phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) enabling the profiling of >7700 microbial species. As more than 30% of them could not previously be quantified at this taxonomic resolution, relative abundance estimates based on mOTUs are more accurate compared to other methods. As a new feature, we show that mOTUs, which are based on essential housekeeping genes, are demonstrably well-suited for quantification of basal transcriptional activity of community members. Furthermore, single nucleotide variation profiles estimated using mOTUs reflect those from whole genomes, which allows for comparing microbial strain populations (e.g., across different human body sites). Metagenomic analysis based on universal phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) is a useful strategy, especially for microbial species without reference genomes. Here, the authors develop mOTUs2, an updated and functionally extended profiling tool for microbial abundance, activity and population profiling.
Drivers and determinants of strain dynamics following fecal microbiota transplantation
Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor–recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice. Understanding the factors underlying colonization of donor microbes in recipients of fecal microbiota transplantation is a necessary first step to aid development of directed approaches that aim to couple colonization to clinical outcomes.
Probing molecular chirality on a sub-femtosecond timescale
Chiral molecules that are non-superimposable mirror images of each other, known as enantiomers, have identical chemical and physical properties unless they interact with another chiral entity, such as chiral light. Chiroptical effects arising from such interactions are used to detect enantiomers in mixtures and to induce enantioselective synthesis and catalysis. Chiroptical effects often arise from the interplay between light-induced electric- and magnetic-dipole transitions in a molecule and evolve on ultrafast electronic timescales. Here we use high-harmonic generation from a randomly oriented gas of molecules subjected to an intense laser field, to probe chiral interactions on these sub-femtosecond timescales. We show that a slight disparity in the laser-driven electron dynamics in the two enantiomers is recorded and amplified by several orders of magnitude in the harmonic spectra. Our work shows that chiroptical detection can go beyond detecting chiral structure to resolving and controlling chiral dynamics on electronic timescales.
Prevalence of serum IgG antibodies against SARS-CoV-2 among clinic staff
The SARS-CoV-2 pandemic threatens health care providers and society. For planning of treatment capacities, it is of major importance to obtain reliable information on infection and fatality rates of the novel coronavirus. A German community study, the so-called Heinsberg study, found a 5-fold higher infection rate (and thus a remarkably lower fatality rate) than the officially reported cases suggest. We were interested to examine the SARS-CoV-2-IgG antibody status among clinic staff of a large neurological center in Northern Germany. Blood samples and questionnaires (demographic data, medical history) were collected pseudonymously. In total, 406 out of 525 (77.3%) of our employees participated in the study. The infection rate among the staff was as high as 2.7%. Including drop-outs (missing questionnaire but test result available), the infection rate was even higher (2.9%). Only 36% of the positively tested employees did suffer from flu-like symptoms in 2020. None of the nurses-having closest and longest contact to patients-were found to be positive. Despite the fact that the infection rate among clinic staff may not be directly compared to the situation in the surrounding county (due to different testing procedures), one might hypothesize that the infection rate could be more than 30-fold higher than the number of officially reported cases for the county of Hameln-Pyrmont. The high rate of IgG-positive, asymptomatic healthcare workers might help to overcome fears in daily work.
Differential Selection for Survival and for Growth in Adaptive Laboratory Evolution Experiments With Benzalkonium Chloride
Biocides are used to control microorganisms across different applications, but emerging resistance may pose risks for those applications. Resistance to biocides has commonly been studied using adaptive laboratory evolution (ALE) experiments with growth at subinhibitory concentrations linked to serial subculturing. It has been shown recently that Escherichia coli adapts to repeated lethal stress imposed by the biocide benzalkonium chloride (BAC) by increased survival (i.e., tolerance) and not by evolving the ability to grow at increased concentrations (i.e., resistance). Here, we investigate the contributions of evolution for tolerance as opposed to resistance for the outcome of ALE experiments with E. coli exposed to BAC. We find that BAC concentrations close to the half maximal effective concentration (EC50, 4.36 μg mL−1) show initial killing (~40%) before the population resumes growth. This indicates that cells face a two‐fold selection pressure: for increased survival and for increased growth. To disentangle the effects of both selection pressures, we conducted two ALE experiments: (i) one with initial killing and continued stress close to the EC50 during growth and (ii) another with initial killing and no stress during growth. Phenotypic characterization of adapted populations showed that growth at higher BAC concentrations was only selected for when BAC was present during growth. Whole genome sequencing revealed distinct differences in mutated genes across treatments. Treatments selecting for survival‐only led to mutations in genes for metabolic regulation (cyaA) and cellular structure (flagella fliJ), while treatments selecting for growth and survival led to mutations in genes related to stress response (hslO and tufA). Our results demonstrate that serial subculture ALE experiments with an antimicrobial at subinhibitory concentrations can select for increased growth and survival. This finding has implications for the design of ALE experiments to assess resistance risks of antimicrobials in different scenarios such as disinfection, preservation, and environmental pollution.
Road Traffic Noise and Incident Myocardial Infarction: A Prospective Cohort Study
Both road traffic noise and ambient air pollution have been associated with risk for ischemic heart disease, but only few inconsistent studies include both exposures. In a population-based cohort of 57 053 people aged 50 to 64 years at enrolment in 1993-1997, we identified 1600 cases of first-ever MI between enrolment and 2006. The mean follow-up time was 9.8 years. Exposure to road traffic noise and air pollution from 1988 to 2006 was estimated for all cohort members from residential address history. Associations between exposure to road traffic noise and incident MI were analysed in a Cox regression model with adjustment for air pollution (NO(x)) and other potential confounders: age, sex, education, lifestyle confounders, railway and airport noise. We found that residential exposure to road traffic noise (L(den)) was significantly associated with MI, with an incidence rate ratio IRR of 1.12 per 10 dB for both of the two exposure windows: yearly exposure at the time of diagnosis (95% confidence interval (CI): 1.02-1.22) and 5-years time-weighted mean (95% CI: 1.02-1.23) preceding the diagnosis. Visualizing of the results using restricted cubic splines showed a linear dose-response relationship. Exposure to long-term residential road traffic noise was associated with a higher risk for MI, in a dose-dependent manner.