Publications

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Publications in peer reviewed journals

6 Publications found
  • Machine learning and phylogenetic analysis allow for predicting antibiotic resistance in M. tuberculosis.

    Yurtseven A, Buyanova S, Agrawal AA, Bochkareva OO, Kalinina OV
    2023 - BMC Microbiol, 23: 404

    Abstract: 

    Antimicrobial resistance (AMR) poses a significant global health threat, and an accurate prediction of bacterial resistance patterns is critical for effective treatment and control strategies. In recent years, machine learning (ML) approaches have emerged as powerful tools for analyzing large-scale bacterial AMR data. However, ML methods often ignore evolutionary relationships among bacterial strains, which can greatly impact performance of the ML methods, especially if resistance-associated features are attempted to be detected. Genome-wide association studies (GWAS) methods like linear mixed models accounts for the evolutionary relationships in bacteria, but they uncover only highly significant variants which have already been reported in literature.
    In this work, we introduce a novel phylogeny-related parallelism score (PRPS), which measures whether a certain feature is correlated with the population structure of a set of samples. We demonstrate that PRPS can be used, in combination with SVM- and random forest-based models, to reduce the number of features in the analysis, while simultaneously increasing models' performance. We applied our pipeline to publicly available AMR data from PATRIC database for Mycobacterium tuberculosis against six common antibiotics.
    Using our pipeline, we re-discovered known resistance-associated mutations as well as new candidate mutations which can be related to resistance and not previously reported in the literature. We demonstrated that taking into account phylogenetic relationships not only improves the model performance, but also yields more biologically relevant predicted most contributing resistance markers.

  • The Fish Pathogen "Candidatus Clavichlamydia salmonicola"-A Missing Link in the Evolution of Chlamydial Pathogens of Humans.

    Collingro A, Köstlbacher S, Siegl A, Toenshoff ER, Schulz F, Mitchell SO, Weinmaier T, Rattei T, Colquhoun DJ, Horn M
    2023 - Genome Biol Evol, 8: in press

    Abstract: 

    Chlamydiae like Chlamydia trachomatis and Chlamydia psittaci are well-known human and animal pathogens. Yet, the chlamydiae are a much larger group of evolutionary ancient obligate intracellular bacteria that includes predominantly symbionts of protists and diverse animals. This makes them ideal model organisms to study evolutionary transitions from symbionts in microbial eukaryotes to pathogens of humans. To this end, comparative genome analysis has served as an important tool. Genome sequence data for many chlamydial lineages are, however, still lacking, hampering our understanding of their evolutionary history. Here, we determined the first high-quality draft genome sequence of the fish pathogen "Candidatus Clavichlamydia salmonicola", representing a separate genus within the human and animal pathogenic Chlamydiaceae. The "Ca. Clavichlamydia salmonicola" genome harbors genes that so far have been exclusively found in Chlamydia species suggesting that basic mechanisms important for the interaction with chordate hosts have evolved stepwise in the history of chlamydiae. Thus, the genome sequence of "Ca. Clavichlamydia salmonicola" allows to constrain candidate genes to further understand the evolution of chlamydial virulence mechanisms required to infect mammals.

  • Genome Dynamics and Temperature Adaptation During Experimental Evolution of Obligate Intracellular Bacteria.

    Herrera P, Schuster L, Zojer M, Na H, Schwarz J, Wascher F, Kempinger T, Regner A, Rattei T, Horn M
    2023 - Genome Biol Evol, 8: in press

    Abstract: 

    Evolution experiments with free-living microbes have radically improved our understanding of genome evolution and how microorganisms adapt. Yet there is a paucity of such research focusing on strictly host-associated bacteria, even though they are widespread in nature. Here, we used the Acanthamoeba symbiont Protochlamydia amoebophila, a distant relative of the human pathogen Chlamydia trachomatis and representative of a large group of protist-associated environmental chlamydiae, as a model to study how obligate intracellular symbionts evolve and adapt to elevated temperature, a prerequisite for the pivotal evolutionary leap from protist to endothermic animal hosts. We established 12 replicate populations under two temperatures (20 °C, 30 °C) for 510 bacterial generations (38 months). We then used infectivity assays and pooled whole-genome resequencing to identify any evolved phenotypes and the molecular basis of adaptation in these bacteria. We observed an overall reduction in infectivity of the symbionts evolved at 30 °C, and we identified numerous nonsynonymous mutations and small indels in these symbiont populations, with several variants persisting throughout multiple time points and reaching high frequencies. This suggests that many mutations may have been beneficial and played an adaptive role. Mutated genes within the same temperature regime were more similar than those between temperature regimes. Our results provide insights into the molecular evolution of intracellular bacteria under the constraints of strict host dependance and highly structured populations and suggest that for chlamydial symbionts of protists, temperature adaptation was facilitated through attenuation of symbiont infectivity as a tradeoff to reduce host cell burden.

  • Metagenomic Antimicrobial Susceptibility Testing from Simulated Native Patient Samples.

    Lüftinger L, Májek P, Rattei T, Beisken S
    2023 - Antibiotics (Basel), 2: in press

    Abstract: 

    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 .

    Halter T, Köstlbacher S, Rattei T, Hendrickx F, Manzano-Marín A, Horn M
    2023 - Microb Genom, 2: in press

    Abstract: 

    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.

    Tveit AT, Söllinger A, Rainer EM, Didriksen A, Hestnes AG, Motleleng L, Hellinger HJ, Rattei T, Svenning MM
    2023 - ISME J, 4: 502-513

    Abstract: 

    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.

Book chapters and other publications

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