Effect of Brucella effector protein BtpB regulating apoptosis by targeting host protein YWHAZ

Abstract Brucella is a successful intracellular bacteria, regulating various physiological activities within host cells by secreting multiple virulence factors. However, the specific molecular mechanisms underlying these processes remain unclear. Through interactions with host proteins, Brucella can influence cellular physiological processes to evade immune responses and enhance the bacteria survival and reproductive abilities. The type IV secretion system (T4SS) of Brucella plays a significant role in the process of Brucella infecting cells. This study revealed the interaction between BtpB and YWHAZ (14–3-3ζ) by analyzing the interaction network of 112 host proteins interacting with Brucella effector protein BtpB. Furthermore, we discovered that BtpB regulates the expression of YWHAZ protein and the deletion of its TIR domain abolishes this interaction as well as the effect on YWHAZ protein expression. Moreover, BtpB activates pro-apoptotic markers leading to apoptosis induction in cells. Our results provide mechanistic evidence that BtpB-dependent apoptosis regulation is contingent upon interaction with YWHAZ, and further characterize YWHAZ as a host factor governing Brucella 's intracellular survival capacity. This study provides valuable understanding of the immune response mechanism against intracellular bacterial infections in hosts and offers a theoretical basis for future prevention and treatment strategies for Brucellosis.