Methods and Challenges of Using the Greater Wax Moth (<i>Galleria mellonella</i>) as a Model Organism in Antimicrobial Compound Discovery

Among non-mammalian infection model organisms, the larvae of the greater wax moth Galleria mellonella have seen increasing popularity in recent years. Unlike other invertebrate models, these larvae can be incubated at 37 &deg;C and can be dosed relatively precisely. Despite the increasing number of publications describing the use of this model organism, there is a high variability with regard to how the model is produced in different laboratories, with respect to larva size, age, origin, storage, and rest periods, as well as dosing for infection and treatment. Here, we provide suggestions regarding how some of these factors can be approached, to facilitate the comparability of studies between different laboratories. We introduce a linear regression curve correlating the total larva weight to the liquid volume in order to estimate the in vivo concentration of pathogens and the administered drug concentration. Finally, we discuss several other aspects, including in vivo antibiotic stability in larvae, the infection doses for different pathogens and suggest guidelines for larvae selection

Structural and functional studies of Escherichia coli Aggregative Adherence Fimbriae (AAF/V) reveal a deficiency in extracellular matrix binding

Enteroaggregative Escherichia coli (EAEC) is an emerging cause of acute and persistent diarrhea worldwide. The pathogenesis of different EAEC stains is complicated, however, the early essential step begins with attachment of EAEC to intestinal mucosa via aggregative adherence fimbriae (AAFs). Currently, five different variants have been identified, which all share a degree of similarity in the gene organization of their operons and sequences. Here, we report the solution structure of Agg5A from the AAF/V variant. While preserving the major structural features shared by all AAF members, only Agg5A possesses an inserted helix at the beginning of the donor strand, which together with altered surface electrostatics, renders the protein unable to interact with fibronectin. Hence, here we characterize the first AAF variant with a binding mode that varies from previously described AAF

Use of tetravalent galabiose for inhibition of Streptococcus suis serotype 2 infection in a mouse model

Peer reviewe

Deep phenotyping of the unselected COPSAC2010 birth cohort study

BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. METHODS: Pregnant women from eastern Denmark were invited during 2008–2010 to a novel unselected ‘COPSAC(2010)’ cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high‐dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. RESULTS: Seven hundred and thirty‐eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over‐representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. CONCLUSIONS: The COPSAC(2010) birth cohort study provides longitudinal clinical follow‐up with highly specific end‐points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle‐related chronic inflammatory disorders such as asthma

Reply to Guy et al.: Support for a bottleneck in the 2011 Escherichia coli O104:H4 outbreak in Germany

In our paper (1), we analyzed isolates from the Escherichia coli O104:H4 outbreaks in Germany and France in May to July 2011. We concluded that, although the German outbreak was larger, the German isolates represent a clade within the greater diversity of the French outbreak. We proposed several hypotheses to explain these findings, including that the lineage leading to the German outbreak went through a narrow bottleneck that purged diversity. Guy et al. (2) report the genomes of eight additional E. coli O104:H4 isolates sampled from the German outbreak. By focusing on the numbers of SNPs in their samples, they suggest that the German outbreak is more diverse than we reported and is similar to the French outbreak. In fact, Guy et al.’s data (2) strongly support our conclusion that the German outbreak represents a clade within the diversity