Title: Multiple in-vitro and in-vivo passaging: ground for evoglutionary adaptability and emergence of hyper-virulent Salmonella strain

Biography:

Diana Pradhan is currently pursuing PhD at NIT Rourkela and working on host pathogen interaction. She has joined PhD in 2014 under supervision of Dr. Vidya Devi Negi, in Laboratory of Infection immunology. She is working in the field of infection biology and has a keen interest in emerging infectious diseases and their prevention. She has experience of working on different models such as C. elegans, Drosophila and Mice. She can work efficiently in cell culture and has expertise in techniques such as molecular biology, flow cytometry, cell biology, microscopy etc.

Abstract

Salmonella infection remains a major health concern across the world because of rise of multiple drug resistant strains and emergence of hyper infectious Salmonella strains leading to disease severity. The outcome of infection is the result of complex interaction of the bug with host immune system as well as in the non-host environments with which Salmonella encounters. We studied the evolutionary adaptation in Salmonella by repeatedly exposing to three different environmental conditions such as in-vitro in LB and F media and in-vivo in C. elegans. We report that this exposure has led to multiple phenotypic and genotypic changes in Salmonella. Compared to unpassaged strain, the passaged strain showed increased body size, increased number of flagella and increased motility that are associated with virulence of Salmonella. Resistance towards the oxidative and nitrosative stresses has also been increased in these strains. Besides, they showed increased invasion and proliferation in different mouse and human cell lines. Further the host colonization of the passaged strains as seen in C. elegans model was found to be more and caused early death of the worms infected with these strains. We looked forward to find the mechanism resulting in the above hyper infectivity phenotype and observed altered cytokine response in the cells infected with these strains along with reduction in the AMP production in the worms possibly leading to hyper proliferation and their early death. Gene expression study revealed that various SPI-I and SPI-II genes, flagellar, stress response and two component systems gene has been upregulated. Furthermore, whole genome sequencing analysis revealed a number of point and frame shifts mutations in the passaged strains. Collectively our study demonstrated the hyper pathogenicity of Salmonella that occurred due to repeated passaging causing disease severity and the genes responsible for the same can be targeted to combat Salmonella infection.