''Brucella suis'' is a

bacterium Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the ...

that causes swine

brucellosis Brucellosis is a zoonosis spread primarily via ingestion of raw milk, unpasteurized milk from infected animals. It is also known as undulant fever, Malta fever, and Mediterranean fever. The bacteria causing this disease, ''Brucella'', are small ...

, a

zoonosis A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When ...

that affects

pig The pig (''Sus domesticus''), also called swine (: swine) or hog, is an omnivorous, domesticated, even-toed, hoofed mammal. It is named the domestic pig when distinguishing it from other members of the genus '' Sus''. Some authorities cons ...

s. The disease typically causes chronic inflammatory lesions in the reproductive organs of susceptible animals or

orchitis Orchitis is inflammation of the testicles. It can also involve swelling, pains, and frequent infection, particularly of the epididymis, as in epididymitis. The term is from the Ancient Greek ὄρχις meaning "testicle"; same root as ''orchid ...

, 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 Spondylitis is an inflammation of the vertebrae. It is a form of spondylopathy. In many cases, spondylitis involves one or more vertebral joints, as well, which itself is called spondylarthritis. __TOC__ Types Pott disease is a tuberculous d ...

, and abscess formation. It is transmitted mainly by ingestion of infected tissues or fluids, semen during breeding, and suckling infected animals. Since

threatens the food supply and causes undulant fever, ''Brucella suis'' and other ''Brucella'' species (''B. melitensis, B. abortus, B. ovis, B. canis'') are recognized as potential agricultural, civilian, and military bioterrorism agents.

Symptoms and signs

The most frequent clinical sign following ''B. 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).

Cause

''Brucella suis'' is a

Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...

, facultative, intracellular

coccobacillus Bacterial cellular morphologies are the shapes that are characteristic of various types of bacteria and often key to their identification. Their direct examination under a light microscope enables the classification of these bacteria (and archae ...

, 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.

Pathogenesis

Phagocytes Phagocytes are cell (biology), cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or Apoptosis, dying cells. Their name comes from the Greek language, Greek ', "to eat" or "devour", and "-cyte", the suffix in ...

are an essential component of the host's

innate immune system The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...

with various antimicrobial defense mechanisms to clear pathogens by oxidative burst, acidification 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 Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

and to deter host immune responses. ''B. suis'' possesses smooth

lipopolysaccharide Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...

(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 In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cel ...

is able to avoid fusion with

lysosomes A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

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 Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

by O-polysaccharides through a

TNF-alpha Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...

-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 acidification 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 In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...

and the synthesis of DnaK chaperones. DnaK is part of the

heat shock protein Heat shock proteins (HSPs) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including ex ...

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 Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...

. Summary: * ''Brucella suis'' encounters a macrophage, but no oxidative burst occurs. * Lipid rafts are necessary for macrophage penetration. * The phagosome rapidly acidifies, creating a stressful environment for bacteria, which triggers activation of virulence genes. * Lipid rafts on phagosomes prevent lysosomal fusion, and normal cell trafficking is unaffected.

Diagnosis

Treatment

Because ''B. suis'' is facultative and intracellular, and is able to adapt to environmental conditions in macrophages, treatment failure and relapse rates are high. The only effective way to control and eradicate zoonosis is by vaccination of all susceptible hosts and elimination of infected animals. The ''Brucella abortus'' (rough LPS ''Brucella'') vaccine, developed for bovine

and licensed by the USDA Animal Plant Health Inspection Service, has shown protection for some swine and is also effective against ''B. suis'' infection, but there is currently no approved vaccine for swine brucellosis.

Biological warfare

In the United States, ''B. suis'' was the first biological agent weaponized in 1952, and was field-tested with ''B. suis''-filled bombs called M33 cluster bombs. It is, however, considered to be one of the agents of lesser threat because many infections are asymptomatic and the mortality is low,Bossi, P., Tegnell, A., Baka, A, Van Loock, F., Hendriks, J., Werner, A., Maidhof, H., Gouvras, G. "Bichat guidelines for the clinical management of brucellosis and bioterrorism-related brucellosis." Eurosurveillance 9 (2004): 1-5. but it is used more as an

incapacitating agent Incapacitating agent is a chemical or biological agent which renders a person unable to harm themselves or others, regardless of consciousness. Lethal agents are primarily intended to kill, but incapacitating agents can also kill if administered ...

References

{{Authority control Swine diseases Bacterial diseases Biological agents Theriogenology Hyphomicrobiales