Among-population variation in drought responses is consistent across life stages but not between native and non-native ranges.

Understanding how widespread species adapt to variation in abiotic conditions across their ranges is fundamental to ecology. Insight may come from studying how among-population variation (APV) in the common garden corresponds with the environmental conditions of source populations. However, there are no such studies comparing native vs non-native populations across multiple life stages. We examined APV in the performance and functional traits of 59 Conyza canadensis populations, in response to drought, across large aridity gradients in the native (North America) and non-native (Eurasia) ranges in three experiments. Our treatment (dry vs wet) was applied at the recruitment, juvenile, and adult life stages. We found contrasting patterns of APV in drought responses between the two ranges. In the native range, plant performance was less reduced by drought in populations from xeric than mesic habitats, but such relationship was not apparent for non-native populations. These range-specific patterns were consistent across the life stages. The weak adaptive responses of non-native populations indicate that they can become highly abundant even without complete local adaptation to abiotic environments and suggest that long-established invaders may still be evolving to the abiotic environment. These findings may explain lag times in invasions and raise concern about future expansions.

Multidrug-resistant isolates from Ukrainian patients in a German health facility: a genomic surveillance study focusing on antimicrobial resistance and bacterial relatedness.

PURPOSE: Antimicrobial resistance is a pressing issue in Ukraine, with healthcare-associated infections caused by multidrug-resistant organisms being a major concern. A recent prospective multicenter study revealed a staggering rate of 48.4% antimicrobial resistance to carbapenems among Enterobacterales causing a healthcare-associated infection. We conducted a systematic survey to investigate the incidence rate and incidence density of carbapenemase-producing Gram-negative bacteria (CPGN) among refugees and war-wounded Ukrainians in connection with the German health system. METHODS: From the onset of the war until November 2022, seven Ukrainian patients were admitted to our hospital. Upon admission, screening samples and samples from the focus of suspected infection were taken from all seven patients. The incidence rate and the incidence density of CPGN were calculated as a result of the microbiological findings. We sequenced all CPGN using Illumina technology. RESULTS: The incidence rate of CPGN at our hospital was 0.06 for 2021 and 0.18 for 2022. All seven Ukrainian patients were infected or colonized with at least one CPGN, including K. pneumoniae (14/25), P. aeruginosa (6/25), A. baumannii (1/25), Providencia stutartii (1/25), C. freundii (1/25), and E. coli (2/25). Genomic surveillance revealed that (i) most frequently detected carbapenemases among all sequenced isolates were blaNDM (17/25) and blaOXA-48 (6/25), (ii) most commonly observed plasmid replicons among the K. pneumoniae isolates recovered from Ukrainian patients were Col(pHAD28) (12/14), IncHI1B(pNDM-MAR) (9/14), IncFIB(pNDM-Mar) (12/14), and (iii) clonal relation between the pathogens of the Ukrainian isolates, but not for the isolates from our hospital surveillance system. CONCLUSION: The rising prevalence of community-acquired colonization and infection with CPGN is having a direct effect on the infection prevention measures, such as higher number of isolations, reprocessing of patient rooms, additional microbiological testing and overall organization within hospitals.

Isolation of Hafnia paralvei co-harbouring blaNDM-1 and blaVIM-1 in a woman who underwent allogeneic hematopoietic stem cell transplantation.

Metallo-ß-lactamases (MBL) are a threat to public health, since they dramatically limit the use of ß-lactams. We report the isolation of a multidrug-resistant Hafnia paralvei strain from urine and a rectal swab of a female patient after allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome. Antimicrobial susceptibility testing yielded resistance to trimethoprim/sulfamethoxazole, colistin, fosfomycin and all ß-lactams, except cefiderocol. Whole genome sequencing revealed the presence of plasmid-encoded NDM-1 and VIM-1 carbapenemases. This finding highlights the importance of epidemiological surveillance and new therapeutic options for MBL.

Temporarily switching from oral to intravenous selexipag in patients with pulmonary arterial hypertension: safety, tolerability, and pharmacokinetic results from an open-label, phase III study.

BACKGROUND: The oral IP receptor agonist selexipag is approved for the long-term treatment of pulmonary arterial hypertension (PAH). Treatment interruptions should be avoided due to the progressive nature of the disease. An intravenous (IV) formulation of selexipag was developed to provide a treatment option for short-term interruptions to oral selexipag. In this prospective, multicenter, open-label study, the safety, tolerability, and pharmacokinetics of temporarily switching between oral and IV selexipag were investigated (NCT03187678, ClinicalTrials.gov). METHODS: PAH patients receiving stable oral selexipag doses were enrolled. Following three consecutive IV selexipag infusions patients resumed oral selexipag. Corresponding IV and oral doses were selected to achieve comparable exposure to the active metabolite of selexipag. Safety outcomes were monitored throughout, and pharmacokinetic samples were obtained after oral and IV administration. RESULTS: All 20 patients completed the study. Fifteen patients had adverse events (AEs), most were mild, and none resulted in discontinuation. Headache was the most common AE throughout the study (four patients). Three serious AEs occurred in two patients with underlying comorbidities when oral dosing had resumed. There were no changes in WHO functional class for any patient and no clinically symptomatic changes in blood pressure were observed. Comparable exposure to the active metabolite of selexipag was demonstrated following corresponding oral and IV selexipag doses. CONCLUSIONS: Temporarily switching between corresponding doses of oral and IV selexipag was well-tolerated with no unexpected safety findings and comparable exposure to the active metabolite. Treatment with IV selexipag is a feasible option to bridge temporary oral selexipag treatment interruptions.

Phylogenetic and functional distinctiveness explain alien plant population responses to competition.

Several invasion hypotheses predict a positive association between phylogenetic and functional distinctiveness of aliens and their performance, leading to the idea that distinct aliens compete less with their resident communities. However, synthetic pattern relationships between distinctiveness and alien performance and direct tests of competition as the driving mechanism have not been forthcoming. This is likely because different patterns are observed at different spatial grains, because functional trait and phylogenetic information are often incomplete, and because of the need for competition experiments that measure demographic responses across a variety of alien species that vary in their distinctiveness. We conduct a competitor removal experiment and parameterize matrix population and integral projection models for 14 alien plant species. More novel aliens compete less strongly with co-occurring species in their community, but these results dissipate at a larger spatial grain of investigation. Further, we find that functional traits used in conjunction with phylogeny improve our ability to explain competitive responses. Our investigation shows that competition is an important mechanism underlying the differential success of alien species.

Use of MALDI-TOF mass spectrometry to detect nosocomial outbreaks of Serratia marcescens and Citrobacter freundii.

MALDI-TOF mass spectrometry (MS) may be used as a rapid typing method for nosocomial pathogens. Here, we evaluated MALDI-TOF MS for discrimination of hospital outbreak-related clusters of Serratia marcescens and carbapenemase-producing Citrobacter freundii. Thirty-three S. marcescens isolates collected from neonatal intensive care unit (NICU) patients, and 23 C. freundii isolates including VIM-positive isolates from a hospital colonization outbreak were measured by Vitek MS. Consensus spectra of each isolate were clustered using SARAMIS software. Genotyping was performed by whole-genome sequencing (WGS). First, a set of 21 S. marcescens isolates from 2014 with seven genotypes including three monoclonal clusters was used for the evaluation of MALDI-TOF typing. MS clustering was largely in agreement with genotyping results when the similarity cut-off for clonal identity was set on 90%. MALDI-TOF cluster analysis was then investigated for the surveillance of S. marcescens in the NICU in 2017 and demonstrated the introduction of new strains into the hospital and nosocomial transmissions. MS analysis of the C. freundii outbreak in 2016 revealed a monoclonal cluster of VIM-positive isolates and the separation of epidemiologically non-related VIM-positive and negative isolates. Two additional VIM-positive Citrobacter isolates from food samples were closely related to the large monoclonal cluster. WGS confirmed the MS results. MALDI-TOF MS may be used as a first-line typing tool for S. marcescens and C. freundii to detect transmission events in the hospital because isolates of an identical WGS type were grouped into the same MS cluster.

A Nosocomial Foodborne Outbreak of a VIM Carbapenemase-Expressing Citrobacter freundii.

Background: A foodborne outbreak of VIM carbapenemase-expressing Citrobacter freundii (CPC) occurred between February 2016 and June 2016 at a major university hospital in Germany. Methods: An explosive increase in CPC isolated from rectal swabs of patients during weekly routine screening led to the declaration of an outbreak. A hospital-wide prevalence screening was initiated as well as screening of all patients on admission and before transfer to another ward, canteen staff, patient rooms, medical and kitchen inventory, and food. Swabs were streaked out on selective plates. All CPC isolates were analyzed using mass spectrometry, and selected isolates were analyzed using whole-genome sequencing. Results: A total of 76 were identified; most were unrelated cases in different wards. The CPC was isolated from retained samples of prepared vegetable salads and puddings and from a mixing machine used to prepare these foods only after an overnight culture. The immediate ban on serving potential source food resulted in a sharp decline and finally disappearance of novel cases. Repeated testing of presliced vegetables showed a high degree of contamination with C. freundii without a carbapenemase, indicating a possible source. Conclusions: An explosive increase in carbapenemase-expressing Enterobacteriaceae contamination may have been caused by a foodborne source, and presliced vegetables should be taken into account as a putative pathogen repository. These findings underline the importance of appropriate cooling, transport, reheating, and distribution of meals and indicate that probing of nonorganic surfaces is limited by low sensitivity, which may be increased by additional overnight cultivation in appropriate media.

In vitro synergism and anti-biofilm activity of ampicillin, gentamicin, ceftaroline and ceftriaxone against Enterococcus faecalis.

Background: Enterococci frequently cause severe biofilm-associated infections such as endocarditis. The combination of ampicillin/ceftriaxone has recently been clinically evaluated as non-inferior compared with the standard therapy of ampicillin/gentamicin for treatment of Enterococcus faecalis endocarditis. Ceftaroline is a novel cephalosporin with enhanced activity against Gram-positive bacteria. Objectives: To compare the in vitro effectiveness of the ceftaroline/ampicillin combination with those of gentamicin/ampicillin and ceftriaxone/ampicillin in planktonic and biofilm cultures of clinical E. faecalis isolates. Methods: Synergistic effects at the planktonic level were analysed by chequerboard assays in 20 E. faecalis isolates. Biofilm-eradicating and biofilm-preventing activities of the antibiotics and their combinations were determined by confocal laser scanning microscopy with quantification by quantitative biofilm analysis (qBA) algorithm and cfu/mL determination. Results: Comparable synergistic effects were observed for both ß-lactam combinations in most isolates, in contrast to gentamicin/ampicillin. However, none of the antibiotic combinations succeeded in eradicating mature biofilms. Gentamicin showed promising biofilm-preventing activity, but at concentrations above those clinically tolerable. The ß-lactams showed a U-shape dose-response relationship in biofilm prevention. Only exposure to cephalosporins caused alterations in cell morphology, which resulted in cell elongation and reclustering in a concentration-dependent manner. Reclustering was associated with high occurrences of small colony variants (SCVs), especially at high ceftriaxone concentrations. Conclusions: This study suggests that combinations of cephalosporins or gentamicin with ampicillin may be advantageous only while bacteraemia persists, whereas combinations have no advantage over monotherapy regarding the treatment of mature biofilms. The selection of SCVs at high ceftriaxone concentrations is worth further study.

Burden of disease studies in the WHO European Region-a mapping exercise.

Background: The World Health Organization (WHO) and the Institute for Health Metrics and Evaluation (IHME) have produced numerous global burden of disease (GBD) estimates since the 1990s, using disability-adjusted life-years (DALYs). Here we attempt to identify studies that have either independent DALY estimates or build on the work of WHO and IHME, for the WHO European Region, categorize them by scope of disease analysis and geographic coverage, and briefly compare their methodology (age weighting, discounting and disability weights). Methods: Google and Google Scholar were used with the search terms 'DALY', 'national burden of disease', Member State names and researcher's names, covering all years. Studies were categorized as: 'specific' (fewer than five disease categories or just risk factors for a single country), 'specific, multicountry' (fewer than five disease categories or just risk factors for more than one country), 'extensive' (covering five or more but not all disease categories for one country), 'full, sub country' (covering all relevant disease categories for part of one country) and 'full, country' (covering all relevant disease categories for one country). Results: A total of 198 studies were identified: 143 'specific', 26 'specific, multicountry', 7 'extensive', 10 'full, sub country' and 12 'full, country' [England (1), Estonia (2), France (1), Romania (1), Serbia (1), Spain (3), Sweden (2) and Turkey (1)]. About 5 (20%) of the 25 examinable 'extensive', 'full, sub country' and 'full, country' studies calculated DALYs using GBD 2010 methodology. Conclusions: Independent burden of diseases studies in Europe have been located, and categorized by scope of disease analysis and geographic coverage. Methodological choices varied between independent 'full, country' studies.

YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers.

YAP1 is a major effector of the Hippo pathway and a well-established oncogene. Elevated YAP1 activity due to mutations in Hippo pathway components or YAP1 amplification is observed in several types of human cancers. Here we investigated its genomic binding landscape in YAP1-activated cancer cells, as well as in non-transformed cells. We demonstrate that TEAD transcription factors mediate YAP1 chromatin-binding genome-wide, further explaining their dominant role as primary mediators of YAP1-transcriptional activity. Moreover, we show that YAP1 largely exerts its transcriptional control via distal enhancers that are marked by H3K27 acetylation and that YAP1 is necessary for this chromatin mark at bound enhancers and the activity of the associated genes. This work establishes YAP1-mediated transcriptional regulation at distal enhancers and provides an expanded set of target genes resulting in a fundamental source to study YAP1 function in a normal and cancer setting.

Long-term effects of grazing and topography on extra-radical hyphae of arbuscular mycorrhizal fungi in semi-arid grasslands.

Grazing and topography have drastic effects on plant communities and soil properties. These effects are thought to influence arbuscular mycorrhizal (AM) fungi. However, the simultaneous impacts of grazing pressure (sheep ha-1) and topography on plant and soil factors and their relationship to the production of extra-radical AM hyphae are not well understood. Our 10-year study assessed relationships between grazing, plant species richness, aboveground plant productivity, soil nutrients, edaphic properties, and AM hyphal length density (HLD) in different topographic areas (flat or sloped). We found HLD linearly declined with increasing grazing pressure (1.5-9.0 sheep ha-1) in sloped areas, but HLD was greatest at moderate grazing pressure (4.5 sheep ha-1) in flat areas. Structural equation modeling indicates grazing reduces HLD by altering soil nutrient dynamics in sloped areas, but non-linearly influences HLD through plant community and edaphic changes in flat areas. Our findings highlight how topography influences key plant and soil factors, thus regulating the effects of grazing pressure on extra-radical hyphal production of AM fungi in grasslands. Understanding how grazing and topography influence AM fungi in semi-arid grasslands is vital, as globally, severe human population pressure and increasing demand for food aggravate the grazing intensity in grasslands.

Bioactivity of topologically confined gramicidin A dimers.

The d-/l-peptide gramicidin A (gA) is well known as a pivotal ion channel model and shows a broad spectrum of bioactivities such as antibiosis, antimalarial activity, as well as hemolysis. We applied inter-chain disulfide bonds to constrain the conformational freedom of gA into parallel and antiparallel dimeric topologies. Albeit the constructs were not found to be monoconformational, CD- and IR-spectroscopic studies suggested that this strategy indeed restricted the conformational space of the d-/l-peptide construct, and that ß-helical secondary structures prevail. Correlative testing of gA dimers in antimicrobial, antimalarial, and ion conduction assays suggested that the tail-to-tail antiparallel single stranded ß6.3 helix dominantly mediates the bioactivity of gA. Other conformers are unlikely to contribute to these activities. From these investigations, only weakly ion conducting gA dimers were identified that retained nM antimalarial activity.

Functional diversity increases ecological stability in a grazed grassland.

Understanding the factors governing ecological stability in variable environments is a central focus of ecology. Functional diversity can stabilize ecosystem function over time if one group of species compensates for an environmentally driven decline in another. Although intuitively appealing, evidence for this pattern is mixed. We hypothesized that diverse functional responses to rainfall will increase the stability of vegetation cover and biomass across rainfall conditions, but that this effect depends on land-use legacies that maintain functional diversity. We experimentally manipulated grazing in a California grassland to create land-use legacies of low and moderate grazing, across which we implemented rainout shelters and irrigation to create dry and wet conditions over 3 years. We found that the stability of the vegetation cover was greatly elevated and the stability of the biomass was slightly elevated across rainfall conditions in areas with histories of moderate grazing. Initial functional diversity-both in the seed bank and aboveground-was also greater in areas that had been moderately grazed. Rainfall conditions in conjunction with this grazing legacy led to different functional diversity patterns over time. Wet conditions led to rapid declines in functional diversity and a convergence on resource-acquisitive traits. In contrast, consecutively dry conditions maintained but did not increase functional diversity over time. As a result, grazing practices and environmental conditions that decrease functional diversity may be associated with lasting effects on the response of ecosystem functions to drought. Our results demonstrate that theorized relationships between diversity and stability are applicable and important in the context of working grazed landscapes.

YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factors.

UNLABELLED: The Yes-associated protein (YAP)/Hippo pathway has been implicated in tissue development, regeneration, and tumorigenesis. However, its role in cholangiocarcinoma (CC) is not established. We show that YAP activation is a common feature in CC patient biopsies and human CC cell lines. Using microarray expression profiling of CC cells with overexpressed or down-regulated YAP, we show that YAP regulates genes involved in proliferation, apoptosis, and angiogenesis. YAP activity promotes CC growth in vitro and in vivo by functionally interacting with TEAD transcription factors (TEADs). YAP activity together with TEADs prevents apoptosis induced by cytotoxic drugs, whereas YAP knockdown sensitizes CC cells to drug-induced apoptosis. We further show that the proangiogenic microfibrillar-associated protein 5 (MFAP5) is a direct transcriptional target of YAP/TEAD in CC cells and that secreted MFAP5 promotes tube formation of human microvascular endothelial cells. High YAP activity in human CC xenografts and clinical samples correlates with increased MFAP5 expression and CD31(+) vasculature. CONCLUSIONS: These findings establish YAP as a key regulator of proliferation and antiapoptotic mechanisms in CC and provide first evidence that YAP promotes angiogenesis by regulating the expression of secreted proangiogenic proteins.

Transitions and invasion along a grazing gradient in experimental California grasslands.

Resilience-based frameworks, founded upon the existence of multiple attractors and regime shifts, have long been applied to complex dynamics of semiarid systems. Utilizing seed addition tests in experimental plantings along grazing gradients, we applied an increase-when-rare criterion to identify bidirectional (states can invade each other) and directional (only one state can invade) transitions among vegetation states characteristic of California grasslands over five years. Annual forage and medusahead grasslands were able to invade each other at all grazing intensities, indicating coexistence. Directional transitions involving invasion of native bunchgrass by other species occurred as grazing intensity increased; recovery (transitions to natives) did not occur at low grazing. While directional transitions at some grazing intensities were accompanied by state persistence at others, we found little evidence for persistence of alternative states at any grazing intensity. Our results suggest that grazing can affect resilience by causing hard-to-reverse transitions, but rarely produces alternative states. However, variation in precipitation seems to dominate grazing responses, supporting the applicability of the nonequilibrium concept in our study system.

World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010.

Illness and death from diseases caused by contaminated food are a constant threat to public health and a significant impediment to socio-economic development worldwide. To measure the global and regional burden of foodborne disease (FBD), the World Health Organization (WHO) established the Foodborne Disease Burden Epidemiology Reference Group (FERG), which here reports their first estimates of the incidence, mortality, and disease burden due to 31 foodborne hazards. We find that the global burden of FBD is comparable to those of the major infectious diseases, HIV/AIDS, malaria and tuberculosis. The most frequent causes of foodborne illness were diarrheal disease agents, particularly norovirus and Campylobacter spp. Diarrheal disease agents, especially non-typhoidal Salmonella enterica, were also responsible for the majority of deaths due to FBD. Other major causes of FBD deaths were Salmonella Typhi, Taenia solium and hepatitis A virus. The global burden of FBD caused by the 31 hazards in 2010 was 33 million Disability Adjusted Life Years (DALYs); children under five years old bore 40% of this burden. The 14 subregions, defined on the basis of child and adult mortality, had considerably different burdens of FBD, with the greatest falling on the subregions in Africa, followed by the subregions in South-East Asia and the Eastern Mediterranean D subregion. Some hazards, such as non-typhoidal S. enterica, were important causes of FBD in all regions of the world, whereas others, such as certain parasitic helminths, were highly localised. Thus, the burden of FBD is borne particularly by children under five years old-although they represent only 9% of the global population-and people living in low-income regions of the world. These estimates are conservative, i.e., underestimates rather than overestimates; further studies are needed to address the data gaps and limitations of the study. Nevertheless, all stakeholders can contribute to improvements in food safety throughout the food chain by incorporating these estimates into policy development at national and international levels.

Mutagenesis of the CTX-M-type ESBL-is MIC-guided treatment according to the new EUCAST recommendations a safe approach?

OBJECTIVES: Spurred by the latest EUCAST and CLSI recommendation to adjust antibiotic therapy on the basis of MICs instead of resistance mechanisms, we aimed to investigate the ability of CTX-M-1 and CTX-M-14 to achieve ceftazidime resistance under selective conditions. METHODS: We exposed Escherichia coli transconjugants bearing natural plasmids that express CTX-M-1, CTX-M-14 or CTX-M-15 to various selective culture conditions and tracked their growth and mutational frequencies. For selected mutants we analysed the sequences of the bla CTX-M genes, determined the altered MICs of cefotaxime, cefepime, ceftazidime and meropenem, and measured the efflux properties and the changes in transcriptional levels of bla CTX-M genes. RESULTS: The CTX-M-1- and CTX-M-14-bearing clones switched from ceftazidime-susceptible to ceftazidime-resistant phenotypes under selective conditions within 24 h. However, no mutations within the bla CTX-M genes were found, and the efflux was unlikely to be involved in the increased ceftazidime MICs. In CTX-M-1-bearing clones bla CTX-M-1 expression was 19-fold increased under ceftazidime-selective conditions but there was a high variance within the clones. Reasons for increased ceftazidime MICs of CTX-M-bearing clones remain unclear but might be the increased enzymatic activity or other intrachromosomal mutations. CONCLUSIONS: It can be speculated that different strategies to survive under selective conditions can be adopted by E. coli, thereby establishing an optimal mechanism with the lowest energy demand for each transconjugant. Based on our in vitro findings, we cannot fully recommend the use of ceftazidime, particularly in critically ill patients with infections due to ESBL producers, regardless of susceptibility to ceftazidime.

Direct RNA-based detection of CTX-M ß-lactamases in human blood samples.

Bloodstream infections with ESBL-producers are associated with increased mortality, which is due to delayed appropriate treatment resulting in clinical failure. Current routine diagnostics for detection of bloodstream infections consists of blood culture followed by species identification and susceptibility testing. In attempts to improve and accelerate diagnostic procedures, PCR-based methods have been developed. These methods focus on species identification covering only a limited number of ESBL coding genes. Therefore, they fail to cover the steadily further evolving genetic diversity of clinically relevant ß-lactamases. We have recently designed a fast and novel RNA targeting method to detect and specify CTX-M alleles from bacterial cultures, based on an amplification-pyrosequencing approach. We further developed this assay towards a diagnostic tool for clinical use and evaluated its sensitivity and specificity when applied directly to human blood samples. An optimized protocol for mRNA isolation allows detection of specific CTX-M groups from as little as 100 CFU/mL blood via reverse transcription, amplification, and pyrosequencing directly from human EDTA blood samples as well as from pre-incubated human blood cultures with a turnaround time for test results of <7 h.

Colonization with extended-spectrum beta-lactamase-producing and carbapenemase-producing Enterobacteriaceae in international travelers returning to Germany.

Two hundred and twenty-five healthy German volunteers traveling to 53 different countries (mostly in Asia, Africa and South America) were enrolled in a prospective cohort study. Stool samples and data on potential travel-associated risk factors (such as type of travel, nutritional habits, occurrence of gastroenteritis) were collected before and after traveling. Screening for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) and carbapenemase-producing Enterobacteriaceae (CPE) was performed using selective media (CHROMagar™ ESBL/CPE plates). Isolates with confirmed ESBL-phenotype were examined for the presence of blaCTX-M, blaTEM, blaSHV, and blaVIM, blaIMP, blaNDM, blaKPC, blaOXA-48 genes by PCR amplification and sequencing. Antimicrobial susceptibility testing was performed using conventional microbroth dilution. Pre-travel analysis of 205 fully evaluable participants revealed an ESBL-PE prevalence rate of 6.8% (14/205). Among 191 participants that were ESBL-negative before travel, 58 (30.4%) were colonized by ESBL-producing Escherichia coli, and 5 (8.6%) additionally carried ESBL-producing Klebsiella pneumoniae upon return. However, no carbapenem-resistant Enterobacteriaceae were detected. ESBL-genotyping revealed that 52/54 (96.6%) E. coli and 4/4 (100%) K. pneumoniae strains available for sequencing produced CTX-M enzymes, mostly CTX-M-15 (33/56, 58.9%), and 2/54 (3.7%) E. coli strains produced SHV-12 enzymes. Travel to India was associated with the highest ESBL-PE acquisition rate (11/15, 73.3%; p=0.015), followed by South East Asia (22/46, 47.8%; p=0.038). Evaluation of travel-associated risk factors demonstrated significance for the occurrence of gastroenteritis (p=0.011). Strictly practiced hand hygiene and exclusive consumption of packaged beverages showed no protective effect. The ESBL-PE persistence rate after 6 months was 8.6% (3/35). We conclude that global efforts are needed to address the further spread of ESBL-PE in the community. Active surveillance and contact isolation precautions may be recommended at admission to medical facilities especially for patients who traveled to India and South East Asia in the previous 6 months.

Herbivore preference drives plant community composition.

Herbivores are important drivers of plant species coexistence and community assembly. However, detailed mechanistic information on how herbivores affect dominance hierarchies between plant species is scarce. Here, we used data of a multi-site herbivore exclusion experiment in grasslands to assess changes in the cover of 28 plant species in response to aboveground pesticide. application. Moreover, we assessed species-specific values of plant defense of these 28 species measured as the performance of a generalist caterpillar, and the preference of the caterpillar and a slug species in no-choice and choice feeding experiments, respectively. We show that more preferred species in the feeding experiments were those that increased in cover after herbivore exclusion in the field, whereas less preferred ones decreased. Herbivore performance and several measured leaf traits were not related to the change in plant cover in the field in response to herbivore removal. Additionally, the generalist slug and the generalist caterpillar preferred and disliked the same plant species, indicating that they perceive the balance between defense and nutritional value similarly. We conclude that the growth-defense trade-off in grassland species acts via the preference of herbivores and that among-species variation in plant growth and preference to herbivores drives plant community composition.