Swine brucellosis

Brucella suis is a bacterium that causes swine brucellosis, a zoonosis that affects pigs. The disease typically causes chronic inflammatory lesions in the reproductive organs of susceptible animals or orchitis, and may even affect joints and other organs. The most common symptom is abortion in pregnant susceptible sows at any stage of gestation. Other manifestations are temporary or permanent sterility, lameness, posterior paralysis, spondylitis, and abscess formation. It is transmitted mainly by ingestion of infected tissues or fluids, semen during breeding, and suckling infected animals. Since brucellosis threatens the food supply and causes undulant fever, Brucella suis and other Brucella species (B. melitensis, B. abortis, B. ovis, B. canis) are recognized as potential agricultural, civilian, and military bioterrorism agents. Brucella suis is a Gram-negative, facultative, intracellular coccobacillus, capable of growing and reproducing inside of host cells, specifically phagocytic cells. They are also not spore-forming, capsulated, or motile. Flagellar genes, however, are present in the B. suis genome, but are thought to be cryptic remnants because some were truncated and others were missing crucial components of the flagellar apparatus. In mouse models, the flagellum is essential for a normal infectious cycle, where the inability to assemble a complete flagellum leads to severe attenuation of the bacteria. Brucella suis is differentiated into five biovars (strains), where biovars 1-3 infect wild boar and domestic pigs, and biovars 1 and 3 may cause severe diseases in humans. In contrast, biovar 2 found in wild boars in Europe shows mild or no clinical signs and cannot infect healthy humans, but does infect pigs and hares. Phagocytes are an essential component of the host’s innate immune system with various antimicrobial defense mechanisms to clear pathogens by oxidative burst, acidificiation of phagosomes, and fusion of the phagosome and lysosome. B. suis, in return, has developed ways to counteract the host cell defense to survive in the macrophage and to deter host immune responses. B. suis possesses smooth lipopolysaccharide (LPS), which has a full-length O-chain, as opposed to rough LPS, which has 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 macrophages does not affect the cell’s normal trafficking. The smooth LPS also inhibits host cell apoptosis by O-polysaccharides through a TNF-alpha-independent mechanism, which allows for B. suis to avoid the activation of the host immune system. Once inside macrophages, B. suis is 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. Since B. suis is unable to grow in a strongly acidic medium, it could be protected from acidification by the ammonia.