Core and accessory genomic traits of Vibrio cholerae O1 drive lineage transmission and disease severity

Maciel-Guerra, Alexandre; Babaarslan, Kubra; Baker, Michelle; Rahman, Aura; Hossain, Maqsud; Sadique, Abdus; Alam, Jahidul; Uzzaman, Salim; Ferdous, Mohammad; Ferdous Rahman Sarker, Mohammad; Sultana, Nasrin; Islam Khan, Ashraful Islam; Begum, Yasmin Ara; Afrad, Mokibul Hassan; Senin, Nicola; Habib, Zakir Hossain; Shirin, Tahmina; Qadri, Firdausi; Dottorini, Tania

Abstract

In Bangladesh, Vibrio cholerae lineages are undergoing genomic evolution, with increased virulence and spreading ability. However, our understanding of the genomic determinants influencing lineage transmission and disease severity remains incomplete. Here, we developed a computational framework using machine-learning, genome scale metabolic modelling (GSSM) and 3D structural analysis, to identify V. cholerae genomic traits linked to lineage transmission and disease severity. We analysed in-patients isolates from six Bangladeshi regions (2015-2021), and uncovered accessory genes and core SNPs unique to the most recent dominant lineage, with virulence, motility and bacteriophage resistance functions. We also found a strong correlation between V. cholerae genomic traits and disease severity, with some traits overlapping those driving lineage transmission. GSMM and 3D structure analysis unveiled a complex interplay between transcription regulation, protein interaction and stability, and metabolic networks, associated to lifestyle adaptation, intestinal colonization, acid tolerance and symptom severity. Our findings support advancing therapeutics and targeted interventions to mitigate cholera spread.

Citation

Maciel-Guerra, A., Babaarslan, K., Baker, M., Rahman, A., Hossain, M., Sadique, A., Alam, J., Uzzaman, S., Ferdous, M., Ferdous Rahman Sarker, M., Sultana, N., Islam Khan, A. I., Begum, Y. A., Afrad, M. H., Senin, N., Habib, Z. H., Shirin, T., Qadri, F., & Dottorini, T. (2024). Core and accessory genomic traits of Vibrio cholerae O1 drive lineage transmission and disease severity. Nature Communications, 15(1), Article 8231. https://doi.org/10.1038/s41467-024-52238-0

• Journal Article Type: Article
• Acceptance Date: Aug 30, 2024
• Online Publication Date: Sep 23, 2024
• Publication Date: Sep 23, 2024
• Deposit Date: Sep 23, 2024
• Publicly Available Date: Sep 24, 2024
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 1
• Article Number: 8231
• DOI: https://doi.org/10.1038/s41467-024-52238-0
• Keywords: Bacterial genomics; Data mining; Epidemiology; Genomics; Machine learning
• Public URL: https://nottingham-repository.worktribe.com/output/39982393
• Publisher URL: https://www.nature.com/articles/s41467-024-52238-0
• Additional Information: Received: 28 March 2024; Accepted: 30 August 2024; First Online: 23 September 2024; : The authors declare no competing interests.