Research Highlight

Genetically engineered cholera bug may yield vaccines, drugs

doi:10.1038/nindia.2020.144 Published online 20 September 2020

Researchers have created several strains from two pathogenic strains of cholera bacterium that they say will be useful for understanding the bacterium’s evolution, and developing novel drugs and vaccines.

The scientists produced the new strains by deleting more than 250 genes with roles in infection and drug resistance. They found that the deleted genes aid in the bacterium’s metabolic functions, contributing to its survival and fitness.

The deleted genes are parts of mobile genetic elements (MGEs), which can move around within a bacterial genome and even across bacterial genomes. However, no previous studies had probed how such genes, if lost, would affect the virulence and survival of cholera pathogens.  

To shed light on this, scientists, including researchers from the Translational Health Science and Technology Institute in Faridabad, India, created multiple strains by removing all the disease-causing and drug-resistance genes from two strains of cholera pathogens isolated from patients in India and Bangladesh. These genes form genomic islands (GIs) and prophages (integrated from viral genome) that are parts of MGEs.   

Such gene deletion, they found, made the strains completely non-pathogenic both in animals and in laboratory growth conditions. Such bacteria didn’t produce any toxins, losing their ability to cause disease in animals.

The researchers, led by Bhabhatosh Das, identified that absence of genes in GIs and prophages reduce the levels of several proteins that perform vital cellular processes for the bacterium. The engineered strains also helped them identify a specific drug target.


References

1. Pant, A. et al. Molecular insights into the genome dynamics and interactions between core and acquired genomes of Vibrio cholera.  Proc. Natl. Acad. Sci. Unit. States. Am. (2020) doi:10.1073/pnas.2006283117