Role of Salmonella typhimurium protein BaeR in aberrant AID expression in B-cell

Abstract

Salmonella, a rod-shaped Gram-negative facultative anaerobe, is one of the most causative agents of food poisoning around the globe. It is a foodborne pathogen that is of paramount concern for public health. It gives rise to 93.8 million food-related illness and 155,000 deaths annually. One of the characteristic manifestations of Salmonella infection is bacteraemia. Salmonella BaeSR is a two-component system composed of a sensor kinase BaeS and a response regulator BaeR that binds to the DNA of the cell and regulates gene expression that functions during the stress response. Reports have shown that BaeR of BaeSR family of two-component system activates multidrug efflux, bacterial virulence activity, as well as other biological functions. Apart from these, BaeR from Salmonella also induces inflammatory responses including switching on of transcription factor nuclear factor-kappa B (NFκB), Janus kinase 2 pathways and the Mitogen-Activated Protein Kinases (MAPKs) thereby contribute to the inflammatory responses. Therefore, we wanted to investigate whether the Salmonella BaeR interacts and modulates the B-cell. And if so, then through which molecular pathway. In order to clearly know the host-pathogen interactions, we wanted to structurally characterise Salmonella BaeR. Our preliminary work indicated that Salmonella BaeR may form a dimer structure. Moreover, when B-cells were stimulated with recombinant BaeR for different time points, we observed that the expression of Activation-Indued Cytidine Deaminase (AID), the enzyme responsible for antibody diversity and specificity was significantly increased. Thus, Salmonella BaeR modulate B-cell biology by upregulating AID expression. Our work hints that the upregulation of AID in B-cells may be associated with different pathological conditions like B-cell lymphoma due to mistargeting of AID that can lead to mutations activating oncogenes in B-cells. Keywords: Salmonella, BaeR, B-cell, Activation-Indued Cytidine Deaminase (AID).