Research Projects

Salmonella enterica serovar Typhimurium (WT-STM) is one of the best-characterised bacterial pathogens; thus it serves as a model organism for studying host-pathogen interactions and intracellular infection mechanisms. Its pathogenesis is tightly regulated by a complex network of genes, many of which are encoded both within and outside the classical Salmonella Pathogenicity Islands (SPIs). There are significant data on the SPI-encoded virulence factors and their role in pathogenesis, recent few studies have highlighted the critical role of non-SPI genes, especially the membrane proteins, which help in sensing environmental signals, mediating nutrient transport, and transducing host-derived cues. Membrane protein remain less explored but are equally vital for bacterial adaptation, intracellular survival, and evasion of host immune responses. Moreover, because membrane proteins are often surface-exposed or embedded in accessible cellular structures, they represent promising targets for therapeutic intervention and vaccine development. Recent advances in antimicrobial strategies have focused on exploiting membrane-associated proteins due to their druggability and essentiality. The target of this study ygiM gene a putative inner membrane protein and in a macrophage infection transcriptomics screen, the gene ygiM, was shown upregulated during intracellular infection. This inner membrane protein YgiM has not yet been functionally analyzed in Salmonella but there are couple of report on E. coli predicting its membrane integration and role of its tail anchor in yeast system. I am trying to understand the importance of this inner membrane gene/protein in virulence regulation and its mechanism. The study will be conducted by using cell line model and in vivo mouse model to understand the important role played by the ygiM gene and protein in bacterial survival and virulence. Insilco approach will be used to identify the interacting target and also the predicting the membrane localisation of the protein. We will also use the overexpression and immunoprecipitation approach to identify the interacting target of the YgiM protein, which can be further chosen to verify the interaction and role in the pathogenesis. In our preliminary study we found that the deletion of the ygiM gene lead to reduced motility, reduced biofilm formation, which are major virulence attributes of the Salmonella pathogenesis. We also found that this gene is conserved in many bacteria. By elucidating the specific function of inner membrane protein YgiM, this study will provide a deeper mechanistic insight into how this protein contributes to infection and pathogenicity in this bacteria. These functional characterizations can help the selection of novel antimicrobial targets, especially those located on or embedded in the bacterial membrane, which are more accessible to drugs and antibodies. Ultimately this study can help to look into the possibility of the target being used for therapeutic approach to combat the Salmonella infection with potential translational applications in diagnostics or as vaccine targets. We can explore the study to find out the importance of this conserved gene across other bacterial species.