bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.04.25.590960

Genome sequence and characterization of a hypervirulent BI/NAP1/027 Clostridioides difficile (CDC20121308)

Espanol, L. A.·Palumbo, M. C.·Barbero, A. M.·Palma, S.·Serral, F.·Ruggeri, D.·Marti, M. A.·Fernandez Do Porto, D.·Hernandez Del Pino, R. E.·Pasquinelli, V.
View original source ↗Export metadata ↓

Abstract

Clostridioides difficile is a gram-positive bacterium implicated in antibiotic-associated diarrhea. The use of antibiotics alters the gut microbiota, rendering the host susceptible to infection by C. difficile. This pathogen colonizes the large intestine of humans and animals leading to asymptomatic carriage or clinical manifestations such as toxic megacolon and fulminant colitis depending on a wide range of pathogen and host factors. The emergence of BI/NAP1/027 strains in North America and the spread of these hypervirulent ribotypes worldwide have been linked to the increase in incidence and severity of C. difficile infections (CDI) over the last decade. In this work, we aimed to characterize the BI/NAP1/027 C. difficile commercial strain CDC20121308 widely employed in the study of host-pathogen interactions. The genome sequence was obtained using a whole-genome shotgun strategy. A total of 3,717 coding sequences (CDS) and 45 tRNAs were predicted. The annotation of the CDC20121308 strain identified 26% of CDS into RAST subsystems. We also detected the presence of RT 027 lineage markers such as thyA, cdtA, cdtB and tcdC 18bp-deletion. Moreover, the genome of CDC20121308 had 11 genes devoted to resistance to toxic compounds, antibiotics (e.g. Tetracycline (Tet) and Vancomycin (Van)) and disinfecting agents as predicted using CARD. C. difficile CDC20121308 resistance to Van and Tet was confirmed by broth microdilution assay. Crystal violet staining demonstrated biofilm formation, which could be associated with antibiotic resistance and pathogenicity. Additionally, we observed a spreading diffuse growth in soft agar tubes, suggesting a motile phenotype. Lastly, a genomic region containing Type 4 Secretory System components such as virD4, virB4, and virB6 was identified. In conclusion, our results allowed a genomic and functional characterization of the BI/NAP1/027 C. difficile CDC20121308 strain. We demonstrated the presence of several genes associated with pathogenesis that were validated by experimental assays. This study provides additional data for the use of this highly virulence commercial strain of epidemiological relevance in research works involving in vitro and in vivo approaches.

Explore related subjects

bioinformaticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Espanol, L. A., Palumbo, M. C., Barbero, A. M., Palma, S., Serral, F., Ruggeri, D., Marti, M. A., Fernandez Do Porto, D., Hernandez Del Pino, R. E., Pasquinelli, V.. 2024-04-28. Genome sequence and characterization of a hypervirulent BI/NAP1/027 Clostridioides difficile (CDC20121308). https://doi.org/10.1101/2024.04.25.590960

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

spatialMET: an open and scalable framework for spatial metabolomics analysis

Mass spectrometry imaging (MSI) enables spatially resolved metabolomics in intact tissue sections, but analysis remains challenging at scale. Existing MSI workflows often require users to combine multiple software tools, while others rely on proprietary vendor software that limits interoperability and reproducibility. To address these challenges, we developed spatialMET, an open-source framework that provides an end-to-end workflow for MSI analysis. spatialMET provides a unified platform for preprocessing, spatial domain detection, and visualization. Downstream analyses include differential abundance testing, spatial autocorrelation and gradient analysis, dimensionality reduction, and correlation network analysis. Spatial domain detection uses hcdist, a C-based hierarchical clustering implementation that substantially reduces runtime and memory use relative to existing R-based approaches. spatialMET can be run through an interactive R Shiny application or as a standalone command-line workflow for larger datasets or high-performance computing environments. Applied to mouse small cell lung cancer MALDI-MSI data containing 284,673 pixels, spatialMET identified tumor-associated, stromal, and adjacent lung spatial domains that aligned with matched histology. Differential abundance analysis identified 117 m/z features that differed between tumor and stromal regions, while spatial autocorrelation analyses revealed spatially structured abundance patterns. Applying spatialMET to mouse lung adenocarcinoma data from an entire lung lobe containing 338,477 pixels further demonstrated scalability and captured spatial heterogeneity across tumor and surrounding lung tissue. In summary, spatialMET provides a scalable, open-source framework for end-to-end spatial metabolomics analysis, and it is distributed as a Docker container for reproducible deployment. Source code and installation instructions are available at https://github.com/biodatalab/spatialMET.

bioinformatics↗
bioRxiv2026

Probing the transcriptome response to shivering in skeletal muscle using a multilayered bioinformatics approach

Cold acclimation holds therapeutic potential for improving metabolic health. We previously demonstrated that repeated cold-induced shivering enhances insulin sensitivity in humans. However, the molecular pathways that underlie the skeletal muscle shivering response, and how these relate to beneficial physiological effects, remain poorly understood. In this study, we combined complementary bioinformatics approaches to allow in-depth analysis of the transcriptomic response of human skeletal muscle to repeated shivering. We identified a robust transcriptional signature and show a sex-specific component in the shivering skeletal muscle response, which seemed to diminish following cold adaptation. Our findings provide mechanistic insights into cold-induced muscle adaptations, shed light on potential interesting molecular targets for further investigation, and emphasize the importance of including both sexes in future cold acclimation studies.

bioinformatics↗
bioRxiv2026

An Information Geometry approach to model topological trajectories and Gene Expression Radius from UMAP geometry.

Understanding the relationship between gene expression dynamics and cellular identity remains a central challenge in single cell biology. Here, we introduce a novel computational and mathematical framework that integrates information geometry, fuzzy topology, and UMAP analysis to model gene expression landscapes derived from single cell RNA sequencing data. We formalize gene expression data as a fuzzy topological space, where interactions between expression points are governed by probabilistic distributions inspired by manifold learning approaches such as UMAP. Within this framework, we define an information geometric structure through a Fisher metric induced by these distributions, enabling the computation of geodesic trajectories that capture cellular differentiation processes. A key contribution of this work is the derivation of analytical conditions, expressed as expression radius formulas, that characterize local neighborhoods in gene expression space. These conditions allow for the identification of genes associated with stem cell states and predictions in transitional cell types in future work. Application of the proposed framework to single cell datasets reveals biologically meaningful gene sets enriched in key regulatory pathways and transcription factors, demonstrating the capacity of our approach to uncover latent structure in complex gene expression data. Our results suggest that integrating differential geometry with statistical learning theory offers a powerful paradigm for modeling genotype and phenotype relationships and cellular state transitions, with potential implications for precision medicine and systems biology.

bioinformatics↗