Brucella BtpB Manipulates Apoptosis and Autophagic Flux in RAW264.7 Cells

Abstract

Brucella transfers effectors into host cells, manipulating cellular processes to its advantage; however, the mechanism by which effectors regulate cellular processes during infection is poorly understood. A growing number of studies have shown that apoptosis and autophagy are critical mechanisms for target cells to cope with pathogens and maintain cellular homeostasis. BtpB is a Brucella type IV secretion system effector with a complex mechanism for manipulating host infection. Here, we show that the ectopic expression of BtpB promoted DNA fragmentation. In contrast, an isogenic mutant strain, ΔbtpB, inhibited apoptosis compared to the wild-type strain B. suis S2 in RAW264.7 cells. In addition, BtpB inhibited autophagy, as determined by LC3-II protein levels, the number of LC3 puncta, and p62 degradation. We also found that BtpB reduced autophagolysosome formation and blocked the complete autophagic flux. Moreover, our results revealed that the autophagy inhibitor, chloroquine, reduces Brucella’s intracellular survival. Overall, our data unveil new mechanisms of virulence implicating the effector BtpB in regulating host intracellular infection.

Helicobacter pylori CagA mediated mitophagy to attenuate the NLRP3 inflammasome activation and enhance the survival of infected cells

“…In these processes, the results of GZ7/GZ7/cagA-infected cells were more signi cant. Although autophagy can limit exogenous infections, it has been reported that bacterial pathogens have evolved mechanisms to interfere with autophagy initiation or autophagy ux for their bene t [32] . Our results presented that H. pylori CagA promotes mitophagy induction but inhibits a speci c stage of autophagosome maturation, causing blocked autophagy ux.…”

Regulation of the Gene for Alanine Racemase Modulates Amino Acid Metabolism with Consequent Alterations in Cell Wall Properties and Adhesive Capability in Brucella spp.

“…Following cellular entry, Brucella induces the formation of Brucella-containing vacuoles, thereby sequestering the bacterium from lysosomal engagement and evading the host immune response. The consequent persistent infection is a major challenge in the treatment and prevention of brucellosis [3]. The initial step in Brucella infection involves adhesion to host cells, which is a pivotal point in the pathogenic cascade, as adhesion is the primary phase in the infectious cycle of most pathogenic bacteria [4].…”

Alr Gene in Brucella suis S2: Its Role in Lipopolysaccharide Biosynthesis and Bacterial Virulence in RAW264.7

“…Infection with the Brucella pathogen results in chronic debilitating diseases in humans and reproductive disorders in animals, with consequent major public health concerns and severe economic losses in the farming sector [ 1 ]. Therefore, a deeper understanding of the pathogenic mechanisms that underlie the Brucella infection is of crucial importance for the prevention and control of brucellosis [ 2 ].…”