Publications
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Publications in peer reviewed journals
Metagenomic Antimicrobial Susceptibility Testing from Simulated Native Patient Samples.
2023 - Antibiotics (Basel), 2: in pressAbstract:
Genomic antimicrobial susceptibility testing (AST) has been shown to be accurate for many pathogens and antimicrobials. However, these methods have not been systematically evaluated for clinical metagenomic data. We investigate the performance of in-silico AST from clinical metagenomes (MG-AST). Using isolate sequencing data from a multi-center study on antimicrobial resistance (AMR) as well as shotgun-sequenced septic urine samples, we simulate over 2000 complicated urinary tract infection (cUTI) metagenomes with known resistance phenotype to 5 antimicrobials. Applying rule-based and machine learning-based genomic AST classifiers, we explore the impact of sequencing depth and technology, metagenome complexity, and bioinformatics processing approaches on AST accuracy. By using an optimized metagenomics assembly and binning workflow, MG-AST achieved balanced accuracy within 5.1% of isolate-derived genomic AST. For poly-microbial infections, taxonomic sample complexity and relatedness of taxa in the sample is a key factor influencing metagenomic binning and downstream MG-AST accuracy. We show that the reassignment of putative plasmid contigs by their predicted host range and investigation of whole resistome capabilities improved MG-AST performance on poly-microbial samples. We further demonstrate that machine learning-based methods enable MG-AST with superior accuracy compared to rule-based approaches on simulated native patient samples.
One to host them all: genomics of the diverse bacterial endosymbionts of the spider .
2023 - Microb Genom, 2: in pressAbstract:
Bacterial endosymbionts of the groups , and are well known for their diverse effects on their arthropod hosts, ranging from mutualistic relationships to reproductive phenotypes. Here, we analysed a unique system in which the dwarf spider is co-infected with up to five different endosymbionts affiliated with , ' Tisiphia' (formerly Torix group ), and . Using short-read genome sequencing data, we show that the endosymbionts are heterogeneously distributed among populations and are frequently found co-infecting spider individuals. To study this intricate host-endosymbiont system on a genome-resolved level, we used long-read sequencing to reconstruct closed genomes of the , '. Tisiphia' and endosymbionts. We provide insights into the ecology and evolution of the endosymbionts and shed light on the interactions with their spider host. We detected high quantities of transposable elements in all endosymbiont genomes and provide evidence that ancestors of the , '. Tisiphia' and endosymbionts have co-infected the same hosts in the past. Our findings contribute to broadening our knowledge about endosymbionts infecting one of the largest animal phyla on Earth and show the usefulness of transposable elements as an evolutionary 'contact-tracing' tool.
Thermal acclimation of methanotrophs from the genus Methylobacter.
2023 - ISME J, 4: 502-513Abstract:
Methanotrophs oxidize most of the methane (CH) produced in natural and anthropogenic ecosystems. Often living close to soil surfaces, these microorganisms must frequently adjust to temperature change. While many environmental studies have addressed temperature effects on CH oxidation and methanotrophic communities, there is little knowledge about the physiological adjustments that underlie these effects. We have studied thermal acclimation in Methylobacter, a widespread, abundant, and environmentally important methanotrophic genus. Comparisons of growth and CH oxidation kinetics at different temperatures in three members of the genus demonstrate that temperature has a strong influence on how much CH is consumed to support growth at different CH concentrations. However, the temperature effect varies considerably between species, suggesting that how a methanotrophic community is composed influences the temperature effect on CH uptake. To understand thermal acclimation mechanisms widely we carried out a transcriptomics experiment with Methylobacter tundripaludum SV96. We observed, at different temperatures, how varying abundances of transcripts for glycogen and protein biosynthesis relate to cellular glycogen and ribosome concentrations. Our data also demonstrated transcriptional adjustment of CH oxidation, oxidative phosphorylation, membrane fatty acid saturation, cell wall composition, and exopolysaccharides between temperatures. In addition, we observed differences in M. tundripaludum SV96 cell sizes at different temperatures. We conclude that thermal acclimation in Methylobacter results from transcriptional adjustment of central metabolism, protein biosynthesis, cell walls and storage. Acclimation leads to large shifts in CH consumption and growth efficiency, but with major differences between species. Thus, our study demonstrates that physiological adjustments to temperature change can substantially influence environmental CH uptake rates and that consideration of methanotroph physiology might be vital for accurate predictions of warming effects on CH emissions.