Life Sciences & Biotechnology
Title : | Development of a computational pipeline to detect cross-species convergence of bacterial gene inactivation via truncation mutations: considering the adaptive evolution of two most predominant pathogens causing urinary tract infections, Escherichia coli and Klebsiella pneumoniae, as a model system |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Microbial Genomics |
Principal Investigator : | Dr. Sujay Chattopadhyay, JIS University, Kolkata, West Bengal |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | sujayc@jisiasr.org |
Details
Executive Summary : | Gene inactivation via truncation or premature stop codon mutations is a common occurrence in bacterial genomes, particularly in obligate symbiotic pathogens. This is often seen as a sign of reductive evolution following 'use-or-lose' dynamics, allowing purging of superfluous traits. However, there are reports suggesting the accumulation of truncation mutations due to adaptive 'die-or-lose' dynamics. This has been sporadically demonstrated through genome-level studies, such as the comparative analysis of two systemically invasive human-restricted serovars, Typhi and Paratyphi A, of Salmonella enterica. The study found an abundance of potentially adaptive truncation mutations, but distinct differences in genes and protein families accumulating those mutations, suggesting recent truncation events after the divergence of each serovar. Biomedical researchers have traditionally focused on laboratory-induced mutations, mostly limited to knockouts. As the era witnesses an exponential growth of bacterial genome sequences in public databases, it is crucial to map naturally occurring adaptive changes, especially those accumulating across diverse allelic backgrounds of different pathogens surviving in the same virulence habitat and/or exerting similar mode of pathogenesis. Detecting adaptive truncation mutations leading to gene inactivation or loss of function is crucial to understand the evolution of bacterial virulence and antibiotic resistance.
Using the model system of these two species as UTI pathogens, the proposal aims to develop a computational pipeline for similar frameworks where different pathogens offer identical clinical manifestations in the same environment but in different time and space. All analysis results will be an online public resource, paving the way for directed functional assays to pinpoint the adaptive role of truncation mutations in E. coli and K. pneumoniae for the pathogenesis of UTI. |
Total Budget (INR): | 6,60,000 |
Organizations involved