Swine Brucellosis - Pathogenesis

Pathogenesis

Phagocytes are an essential component of the host’s innate immune system with various anti-microbial defense mechanisms to clear pathogens via oxidative burst, acidificiation of phagosomes, and fusion of the phagosome and lysosome. B. suis, in retun, have developed ways to counteract the host cell defense to survive in the macrophage and to deter host immune responses.

Brucella suis possess smooth lipopolysaccharide (LPS), which have a full length O-chain, as opposed to rough LPS, which have a truncated or no O-chain. This structural characteristic allows for B. suis to interact with lipid rafts on the surface of macrophages to be internalized, and the formed lipid rich phagosome is able to avoid fusion with lysosomes through this endocytic pathway. In addition, this furtive entry into the macrophage does not affect the cell’s normal trafficking. The smooth LPS also inhibits host cell apoptosis via O-polysaccharides through a TNF-alpha independent mechanism, which allows for B. suis to avoid the activation of the host immune system.

Once inside the macrophage, B. suis are able to endure the rapid acidificiation in the phagosome to pH 4.0-4.5 by expressing metabolism genes mainly for amino acid synthesis. The acidic pH is actually essential for replication of the bacteria by inducing major virulence genes of the virB operon and the synthesis of DnaK chaperones. DnaK is part of the heat shock protein 70 family and aids in the correct synthesis and activation of certain virulence factors.

In addition, the B. suis gene for nickel transport, nikA, is activated by metal ion deficiency and is expressed once in the phagosome. Nickel is essential for many enzymatic reactions including ureolysis to produce ammonia which in turn may neutralize acidic pH. It is suggested that since B. suis is unable to grow in strongly acidic medium, it could be protected from acidification by the ammonia.

Summary:

• B. suis encounters macrophage, but no oxidative burst occurs
• lipid rafts are necessary for macrophage penetration
• phagosome rapidly acidifies creating stressful environment for bacteria which triggers activation of virulence genes
• lipid rafts on phagosomes prevent lysosomal fusion and normal cell trafficking is unaffected