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

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

Research output: Journal PublicationArticlepeer-review

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.

Original languageEnglish
Article number8231
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - Dec 2024

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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