In Brief | Infectious Diseases, Vaccines & Antimicrobials
Harnessing Machine Learning to Decode Cholera: A Study of Vibrio cholerae’s Evolutionary Adaptations in Bangladesh
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Originally Published: 23 September 2024
Sourced: Nature Communications
Type of article: In Brief
MedED Catalogue Reference: MpIB0013
Category: Infectious Diseases, Vaccines & Antimicrobials
Cross Reference: Genetics, Machine Learning
Keywords: cholera, machine learning,
Genomic analysis revealed unique traits of Vibrio cholerae lineages linking recent mutations to increased virulence, transmission, and disease severity.
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Originally published in Nature Communications, 23 September 2024
Cholera is an acute diarrheal disease affecting an estimated 1.3 billion people worldwide, leading to approximately 1.3 to 4 million cases annually, with 21,000 to 143,000 deaths. In Bangladesh, where cholera is endemic, about 66 million people are at risk, with at least 100,000 cases and 4,500 deaths reported each year.
The global burden of cholera is primarily attributed to the O1 serogroup, divided into two main serotypes, Ogawa and Inaba, and further categorized into classical and El Tor biotypes, each exhibiting distinct genetic and phenotypic characteristics.
Recent studies indicate that Vibrio cholerae (V.cholerae) lineages in Bangladesh are undergoing significant genomic evolution, resulting in increased virulence and transmission capabilities. However, the genomic determinants influencing these changes remain poorly understood.
This study utilized a computational framework that combines machine learning, genome-scale metabolic modelling (GSMM), and 3D structural analysis to identify genomic traits associated with lineage transmission and disease severity.
The study examined two V.cholerae lineages, BD-2 and the emergent BD-1.2, responsible for recent outbreaks.
By analyzing patient isolates from six regions between 2015 and 2021, the researchers uncovered unique accessory genes and core SNPs linked to virulence, motility, and bacteriophage resistance.
The following findings were determined:
Notably, the findings confirmed known mutations and identified additional ones unique to each lineage, particularly in genes involved in toxin transport and acid tolerance.
Specific mutations in five core genes associated with BD-1.2 were highlighted, emphasizing their role in the lineage's increased prevalence. For instance, a mutation in the ompU gene was linked to bacteriophage resistance, enhancing BD-1.2 virulence.
Additionally, 12 accessory genes unique to BD-1.2 contributed to antibiotic resistance and biofilm formation. V. cholerae's capacity to form biofilm aggregates during infection emphasizes its role in pathogenesis.
Regulatory networks influencing lineage differentiation were explored, revealing significant SNPs in transcription factor binding sites (TFBs) regulating virulence gene expression. This suggests a connection between genetic variation and bacterial adaptability in the gut.
Overall, this study uncovered a complex interplay of genetic factors influencing V. cholerae pathogenicity and transmission dynamics, providing insights into disease severity and highlighting the need for further experimental studies to investigate these findings.
This research represents a significant step toward understanding cholera's genomic diversity and potential therapeutic targets.
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