TY - JOUR
T1 - Core and accessory genomic traits of Vibrio cholerae O1 drive lineage transmission and disease severity
AU - Maciel-Guerra, Alexandre
AU - Babaarslan, Kubra
AU - Baker, Michelle
AU - Rahman, Aura
AU - Hossain, Maqsud
AU - Sadique, Abdus
AU - Alam, Jahidul
AU - Uzzaman, Salim
AU - Ferdous Rahman Sarker, Mohammad
AU - Sultana, Nasrin
AU - Islam Khan, Ashraful
AU - Ara Begum, Yasmin
AU - Hassan Afrad, Mokibul
AU - Senin, Nicola
AU - Hossain Habib, Zakir
AU - Shirin, Tahmina
AU - Qadri, Firdausi
AU - Dottorini, Tania
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85204870129&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-52238-0
DO - 10.1038/s41467-024-52238-0
M3 - Article
C2 - 39313510
AN - SCOPUS:85204870129
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 8231
ER -