BSB PhD Exit Seminar: Study of bacteriophage encoded glucosyltransferase genes (gtr) in Shigella flexneri serotype 1c

Shigella flexneri serotype 1c is a predominant serotype causing shigellosis in developing countries. It has a unique and highly modified O-antigen structure comprising of at least two distinct O-antigen modifying gene clusters (gtrI and gtrIc). These genes are encoded by two different bacteriophages; gtrIgene cluster mediates the addition of the first glucosyl group at the N-acetyl-glucosamine residue of O-antigen whereas the gtrIc gene cluster mediates the addition of the second glucosyl group resulting in the serotype 1c-specific O-antigen modification.

My PhD research involved the development of high quality complete reference genome of S. flexneri serotype 1c (strain Y394). We identified several hypothetical genes and putative bacteriophage regions in Y394 genome, which warrants future investigation for determining the role of these unknown genes in relevance to pathogen virulence and survival in the host environment. I also performed population and phylogenetic analysis of S. flexneri serotype 1c using whole genome sequences of over 80 clinical isolates isolated from different geographical regions around the globe. Later part of my PhD aimed at studying the role of two gtr gene clusters in S. flexneri virulence. Different virulence assays were performed using Y394 and two isogenic mutants: gtrI knockout and gtrIc knockout. The virulence assays included the use of Caenorhabditis elegans as an in vivo model to study the ability of bacteria to infect the epithelial intestinal cells and use of HeLa cells as an in vitro model to study the invasion of the host cells alongside biofilm assay. This study showed that the addition of an extra glucosyl group at the N-acetyl-glucosamine residue of O-antigen has a significant impact on the virulence of S. flexneri serotype 1c. 


I joined the Verma lab in early 2016 for my PhD with an Endeavour Scholarship sponsored by the Australian Government Department of Education and Training. Before joining ANU, I worked as a research assistant at the Mycobacterial Research Laboratory, the Leprosy Mission Nepal. I completed my BSc in Microbiology from Tribhuvan University, Nepal and MSc in Biotechnology from Osmania University, India.