Biology subjects

Franz, E.

Publications and source records attributed to Franz, E..

7 recordsLinked to original sources

bioRxiv2026

Population analysis and host-disease associations of Shiga toxin-producing Escherichia coli from various sources across eleven European countries using whole genome sequencing

Shiga toxin-producing Escherichia coli (STEC) are important foodborne pathogens, able to cause severe disease in humans. In the DiSCoVeR project (https://onehealthejp.eu/jrp-discover/) a STEC inventory from human and non-human sources from 11 European countries was set up and [≥] 3500 strains were sequenced to perform comparative genomics analysis. We used this dataset to assess STEC population structure and to investigate potential associations between genomic features, host reservoirs and symptoms. Most STEC isolates analysed by Whole Genome Sequencing (WGS) in this study were collected between years 2010-2020. An ad hoc pipeline was deployed for a harmonised characterization of the STEC in the database, allowing the determination of serotyping, stx gene subtyping, 7-loci MLST, virulotyping and cgMLST. The results were analysed with Principal Component Analysis (PCoA) in relation with isolation source to assess clustering of STEC subpopulations. When human STEC data were analysed, the PCoA revealed three distinct human STEC subpopulations (STEC_1, STEC_2 and STEC_3), which were further analysed for associations between genomic features, symptoms and variance. The non-human STEC showed a more dispersed distribution, except for one subpopulation with genes linked to specific host species, and some virulence profiles overlapping with the STEC_1 population. In conclusion, our analysis identified distinct STEC subpopulations from human cases, each characterized by specific genetic features and associated with varying proportions of severe disease outcomes. These findings provide novel insights supporting the risk assessment of STEC. Impact statement[This lay summary of your article should be no more than 200 words, and should a) provide a perspective of how this article adds to the literature in the field; b) identify breadth of interest/utility; and c) state the significance of output (incremental or step), in terms of relevance.] This study is based on the establishment of a One Health STEC genomes database, including sequences from isolates of different sources. Most of the isolates had been isolated in the ten-years time span 2010-2020, in 11 different countries, for surveillance and monitoring activities or specific surveys and research purposes. The final dataset included the whole genome sequencing of 3,418 STEC isolates, mainly from human cases of infections. The metadata included the host symptoms, where available, for human STEC strains and the animal source the strains had been isolated from. We set up a pipeline for the harmonized analysis of STEC WGS, called Discover, made available though ARIES webserver or GitHub. The analysis allowed a deep characterization of STEC strains circulating in Europe. We used this resource to assess STEC population structure and to investigate potential associations between genomic features, host reservoirs, and various symptoms associated with STEC infection by PCoA. This analysis highlighted the presence of subpopulation of human STEC associated with specific features. We provide new information useful for risk characterization, as well as a large dataset genome database and associated metadata compiled from STEC strains, representing a valuable resource for the scientific community, enabling further investigations into STEC diversity, evolution, source attribution and public health relevance. Data summaryThe authors confirm all supporting data, including sequence data accession numbers, code and protocols have been provided within the article or through supplementary data files. One supplementary method and five supplementary tables are available with the online version of this article

genomics↗

bioRxiv2024

Genome Analyses of A Worldwide Multisource Collection of Klebsiella variicola Reveal Adaptation Relevant for Human Infection

AO_SCPLOWBSTRACTC_SCPLOWKlebsiella variicola (K.var), part of the Klebsiella pneumoniae (K.pne) species complex, is an emerging human pathogen originally associated with plants. Phylogenomic analyses of a global dataset of isolates categorised as human, animal, plant, or environmental strains suggest that K.var are broadly disseminated regardless of hosts or habitats and exhibit genomic variability that is relevant for occupying and transmitting within and across multiple sources. Ancestral state analyses confirm that K.var are originally derived from non-human sources. Genome-wide association analyses of human versus non-human isolates of K.var indicate isolates from human origins are linked to the loss of cold-shock response genes such as lpxP and cspB. Importantly, human K.var isolates also showed enriched antimicrobial resistance gene content and diversity acquired through mobile genetic elements, horizontal gene transfer and mutations within the chromosomal loci which underscore the impact of antimicrobial exposure and proximity to antibiotic resistant K.pne in nosocomial environments. Capsular profiles of K.var suggest high levels of variability in gene composition and indicate that gene functionality for wcaJ in capsule formation differs between K.var and K.pne. Although capsular specialisation was not observed in a host/habitat or lineage-dependent manner, human isolates harbour, on average, a higher siderophore gene content in addition to mrkD mutations which impact on fimbriae and biofilm formation. There is limited evidence of any specific K.var lineages exhibiting convergence of both virulence and antimicrobial resistance genotypes which suggest that these attributes are evolving independently in clinical strains. Our work highlights that gene attrition and acquisition provide a basis for adaptation of K.var as human pathogens. The broad distribution and evolution of K.var highlight the need for improved diagnostic precision and surveillance under a One Health framework.

microbiology↗

bioRxiv2023

Colon cancer and cell transformation by clinical Salmonella strains are associated with bacterial virulence and intracellular fitness

Non-typhoidal Salmonella (NTS) are facultative intracellular pathogens that are associated epidemiologically and experimentally with colon cancer development. Yet, the driving factors of Salmonella-induced cell transformation are mostly unknown. We compared 30 (case) NTS clinical strains isolated from patients who were diagnosed with colon cancer >1 year after NTS infection, versus 30 (control) strains from patients who did not develop colon cancer. While we observed diverse cell invasion and transformation efficiencies among the 60 NTS strains, case strains showed higher transformation efficiency than matching control strains. Genomic and transcriptomic analyses showed that transformation efficiency could not be attributed to specific genomic features, but was associated with gene expression, particularly metabolic genes and regulons. Moreover, high-transforming NTS strains display increased capacity to utilize various nutrient sources, including carbohydrates and amino acids, and grow significantly faster intracellularly than low-transforming NTS. Our results link NTS intracellular virulence to cancer promotion. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/562874v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@137c6bcorg.highwire.dtl.DTLVardef@d874c1org.highwire.dtl.DTLVardef@d94b22org.highwire.dtl.DTLVardef@1d3e11c_HPS_FORMAT_FIGEXP M_FIG C_FIG In briefNon-typhoidal Salmonella (NTS) infections can promote cell transformation and colon cancer progression. Yet, little is known about the driving factors of Salmonella-induced transformation. Stevenin et al. performed a multi-omic characterization of clinical NTS strains identified in a nation-wide epidemiological study as associated with colon cancer and revealed a link between bacterial virulence, intracellular fitness, and host cell transformation. Highlights- Cancer-associated clinical NTS generate more cell transformation than matching control NTS. - NTS transformation efficiency did not correlate with specific genetic features. - NTS transformation efficiency correlates with gene expression and bacterial metabolic needs. - High-transforming NTS display increased virulence and intracellular fitness.

microbiology↗

bioRxiv2021

phylogatR: Phylogeographic data aggregation and repurposing

Patterns of genetic diversity within species contain information about the history of that species, including how they have responded to historical climate change and how easily the organism is able to disperse across its habitat. More than 40,000 phylogeographic and population genetic investigations have been published to date, each collecting genetic data from hundreds of samples. Despite these millions of data points, meta-analyses are challenging because the synthesis of results across hundreds of studies, each using different methods and forms of analysis, is a daunting and time-consuming task. It is more efficient to proceed by repurposing existing data and using automated data analysis. To facilitate data repurposing, we created a database (phylogatR) that aggregates data from different sources and conducts automated multiple sequence alignments and data curation to provide users with nearly ready-to-analyze sets of data for thousands of species. Two types of scientific research will be made easier by phylogatR, large meta-analyses of thousands of species that can address classic questions in evolutionary biology and ecology and student- or citizen-science based investigations that will introduce a broad range of people to the analysis of genetic data. phylogatR enhances the value of existing data via the creation of software and web-based tools that enable these data to be recycled and reanalyzed and increase accessibility to big data for research labs and classroom instructors with limited computational expertise and resources.

bioinformatics↗

bioRxiv2021

Asymptomatic gut colonization by extended-spectrum beta-lactamase-producing Escherichia coli is not associated with an altered gut microbiome or metabolome in Dutch adults

BackgroundGut colonization by antibiotic resistant E. coli strains, including extended-spectrum beta-lactamase (ESBL)-producing E. coli is a risk factor for developing overt infection. The gut microbiome can provide colonization resistance against enteropathogens, but it remains unclear whether it confers resistance against potentially pathogenic ESBL-producing E. coli. MaterialsFrom a Dutch cross-sectional population study (PIENTER-3), feces from 2751 individuals were used to culture ESBL-producing bacteria. Of these, we selected 49 samples which were positive for an ESBL-producing Escherichia coli (ESBL+), and negative for a variety of variables known to affect microbiome composition. These were matched in a 1:1 ratio to ESBL- samples based on age, sex, having been abroad in the past six months and ethnicity. Shotgun metagenomic sequencing was performed and taxonomic species composition and functional annotations (microbial metabolism and carbohydrate-active enzymes) were determined. Targeted quantitative metabolic profiling (1H NMR-spectroscopy) was performed to investigate metabolomic profiles. ResultsNo differences in alpha or beta diversity were observed, nor in relative abundance, between ESBL+ and ESBL- individuals based on bacterial species level composition. Machine learning approaches based on microbiota composition did not accurately predict ESBL status (area under the receiver operating characteristic curve (AUROC)=0.53), neither when based on functional profiles. The metabolome did also not convincingly differ between ESBL groups as assessed by a variety of approaches, including machine learning through random forest (AUROC=0.61). ConclusionUsing a combination of multi-omics and machine learning approaches, we conclude that asymptomatic gut carriage of ESBL-producing E. coli is not associated with an altered microbiome composition or function. This may suggest that microbiome-mediated colonization resistance against ESBL-producing E. coli is not as relevant as it is against other enteropathogens.

microbiology↗

bioRxiv2020

Emergence and global spread of Listeria monocytogenes main clinical clonal complex

Retracing microbial emergence and spread is essential to understanding the evolution and dynamics of pathogens. The bacterial foodborne pathogen Listeria monocytogenes clonal complex 1 (Lm-CC1) is the most prevalent clonal group associated with listeriosis, and is strongly associated with cattle and dairy products. Here we analysed 2,021 Lm-CC1 isolates collected from 40 countries, since the first Lm isolation to the present day, to define its evolutionary history and population dynamics. Our results suggest that Lm-CC1 spread worldwide from North America following the Industrial Revolution through two waves of expansion, coinciding with the transatlantic livestock trade in the second half of the 19th century and the rapid growth of cattle farming in the 20th century. Lm-CC1 then firmly established at a local level, with limited inter-country spread. This study provides an unprecedented insight into Lm-CC1 phylogeography and dynamics and can contribute to effective disease surveillance to reduce the burden of listeriosis.

genomics↗

bioRxiv2020

Osteosarcoma tumors maintain intertumoral heterogeneity, even while adapting to environmental pressures that drive clonal selection

BackgroundTumors are complex tissues containing collections of phenotypically diverse malignant and nonmalignant cells. We know little of the mechanisms that govern heterogeneity of tumor cells nor of the role heterogeneity plays in overcoming stresses, such as adaptation to different microenvironments. Osteosarcoma is an ideal model for studying these mechanisms--it exhibits widespread inter- and intra-tumoral heterogeneity, predictable patterns of metastasis, and a lack of clear targetable driver mutations. Understanding the processes that facilitate adaptation to primary and metastatic microenvironments could inform the development of therapeutic targeting strategies. ResultsWe investigated single-cell RNA-sequencing profiles of 47,977 cells obtained from cell line and patient-derived xenograft models as cells adapted to growth within primary bone and metastatic lung environments. Tumor cells maintained phenotypic heterogeneity as they responded to the selective pressures imposed during bone and lung colonization. Heterogenous subsets of cells defined by distinct transcriptional profiles were maintained within bone- and lung-colonizing tumors, despite high-level selection. One prominent heterogenous feature involving glucose metabolism was clearly validated using immunofluorescence staining. Finally, using concurrent lineage tracing and single-cell transcriptomics, we found that lung colonization enriches for multiple clones with distinct transcriptional profiles that are preserved across cellular generations. ConclusionsResponse to environmental stressors occurs through complex and dynamic phenotypic adaptations. Heterogeneity is maintained, even in conditions that enforce clonal selection. These findings likely reflect the influences of developmental processes promoting diversification of tumor cell subpopulations, which are retained, even in the face of selective pressures.

cancer biology↗