Swine brucellosis
Encyclopedia
Swine brucellosis is a zoonosis affecting pigs, caused by the bacteria Brucella suis. 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 hosts 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. In humans, it can cause undulant fever.
Since brucellosis
threatens food supply and cause 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.
, facultative
intracellular coccobacilli and therefore are capable of growing and reproducing inside of host cells, specifically phagocytic cells. They are also non-spore-forming, non-capsulated, and non-motile. Flagellar
genes, however, are present in the B. suis genome, but thought to be cryptic remnants because some were truncated and others were missing crucial components of the flagellar apparatus. Interestingly, in mouse models, studies have shown that 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 are differentiated into five biovars (strains), where bv. 1-3 infect boars and pigs and bv.1 and 3 may cause severe diseases in humans. In contrast, bv. 2 found in wild boars in Europe show mild or no clinical signs and cannot infect healthy humans, but do infect pigs and hares.
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:
Swine also develop orchitis (swelling of the testicles), lameness (movement disability), hind limb paralysis, or spondylitis (inflammation in joints).
. It is, however, considered to be one of the agents of lesser threat because many infections are asymptomatic and the mortality is low, but it is used more as an incapacitating agent.
Orchitis
Orchitis or orchiditis is a condition of the testes involving inflammation. It can also involve swelling and frequent infection.-Symptoms:Symptoms of orchitis are similar to those of testicular torsion...
and may even affect joints and other organs. The most common symptom is abortion in pregnant susceptible hosts at any stage of gestation. Other manifestations are temporary or permanent sterility, lameness, posterior paralysis, spondylitis
Spondylitis
Spondylitis is an inflammation of the vertebra. It is a form of spondylopathy. In many cases, spondylitis involves one or more vertebral joint as well, which itself is called spondylarthritis.-Examples:...
, and abscess formation. It is transmitted mainly by ingestion of infected tissues or fluids, semen during breeding, and suckling infected animals. In humans, it can cause undulant fever.
Since brucellosis
Brucellosis
Brucellosis, also called Bang's disease, Crimean fever, Gibraltar fever, Malta fever, Maltese fever, Mediterranean fever, rock fever, or undulant fever, is a highly contagious zoonosis caused by ingestion of unsterilized milk or meat from infected animals or close contact with their secretions...
threatens food supply and cause 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.
Etiology
B. suis are gram-negativeGram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
, facultative
Facultative
Facultative means "optional" or "discretionary" , used mainly in biology in phrases such as:* Facultative anaerobe, an organism that can use oxygen but also has anaerobic methods of energy production...
intracellular coccobacilli and therefore are capable of growing and reproducing inside of host cells, specifically phagocytic cells. They are also non-spore-forming, non-capsulated, and non-motile. Flagellar
Flagellum
A flagellum is a tail-like projection that protrudes from the cell body of certain prokaryotic and eukaryotic cells, and plays the dual role of locomotion and sense organ, being sensitive to chemicals and temperatures outside the cell. There are some notable differences between prokaryotic and...
genes, however, are present in the B. suis genome, but thought to be cryptic remnants because some were truncated and others were missing crucial components of the flagellar apparatus. Interestingly, in mouse models, studies have shown that 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 are differentiated into five biovars (strains), where bv. 1-3 infect boars and pigs and bv.1 and 3 may cause severe diseases in humans. In contrast, bv. 2 found in wild boars in Europe show mild or no clinical signs and cannot infect healthy humans, but do infect pigs and hares.
Pathogenesis
Phagocytes are an essential component of the host’s innate immune systemInnate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
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
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
and to deter host immune responses.
Brucella suis possess smooth lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
(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
Phagosome
In cell biology, a phagosome is a vacuole formed around a particle absorbed by phagocytosis. The vacuole is formed by the fusion of the cell membrane around the particle. A phagosome is a cellular compartment in which pathogenic microorganisms can be killed and digested...
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
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
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
Operon
In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create...
and the synthesis of DnaK chaperones. DnaK is part of the heat shock protein
Heat shock protein
Heat shock proteins are a class of functionally related proteins involved in the folding and unfolding of other proteins. Their expression is increased when cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated...
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
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
.
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
Symptoms
The most frequent clinical sign following Brucella suis infection is abortion in pregnant females, reduced milk production, and infertility. Cattle can also be transiently infected when they share pasture or facilities with infected pigs and B. suis can be transmitted by cow’s milk.Swine also develop orchitis (swelling of the testicles), lameness (movement disability), hind limb paralysis, or spondylitis (inflammation in joints).
Treatment
Because Brucella suis are facultative intracellular and are able to adapt to environmental conditions in the macrophage, treatment failure and relapse rates are high. The only effective way to control and eradicate zoonosis is by vaccination of all susceptible hosts and elmination of infected animals. The Brucella abortus (rough LPS Brucella) vaccine, developed for bovine brucellosis is licensed by the USDA Animal Plant Health Inspection Service, has shown protection for some swine and is also effective against B. suis infection, however, there is currently no approved vaccine for swine brucellosis.Biological warfare
In the United States, Brucella suis was the first biological agent weaponized in 1952 and was field-tested with B. suis-filled bombs called M33 cluster bombM33 cluster bomb
The M33 cluster bomb, also known as the Brucella cluster bomb, was a U.S. biological cluster bomb developed in the early 1950s and deployed in 1952. It was the first standardized biological weapon in the U.S. arsenal.-History:...
. It is, however, considered to be one of the agents of lesser threat because many infections are asymptomatic and the mortality is low, but it is used more as an incapacitating agent.