Swine brucellosis

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Swine brucellosis
Brucella suis culture.jpg
Brucella suis culture
Scientific classification Red Pencil Icon.png
Domain: Bacteria
Phylum: Proteobacteria
Class: Alphaproteobacteria
Order: Rhizobiales
Family: Brucellaceae
Genus: Brucella
Species:
B. suis
Binomial name
Brucella suis
Huddleson, 1929

Swine brucellosis is a zoonosis affecting pigs, caused by the bacterium 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. [1] The most common symptom is abortion in pregnant susceptible sows at any stage of gestation. [2] 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. [3]

Orchitis is inflammation of the testes. 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.

Spondylitis is an inflammation of the vertebra. It is a form of spondylopathy. In many cases, spondylitis involves one or more vertebral joints as well, which itself is called spondylarthritis.

Contents

Since brucellosis threatens the food supply and causes undulant fever, [4] Brucella suis and other Brucella species (B. melitensis, B. abortis, B. ovis, B. canis ) are recognized as potential agricultural, civilian, and military bioterrorism agents. [5]

Brucellosis Human disease

Brucellosis is a highly contagious zoonosis caused by ingestion of unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions. It is also known as undulant fever, Malta fever, and Mediterranean fever.

Cause

Brucella suis is a Gram-negative, facultative, intracellular coccobacillus, capable of growing and reproducing inside of host cells, specifically phagocytic cells. [6] They are also not spore-forming, capsulated, or motile. [6] Flagellar genes, however, are present in the B. suis genome, but are thought to be cryptic remnants because some were truncated and others were [6] missing crucial components of the flagellar apparatus. [7] [8] 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. [9]

Facultative means "optional" or "discretionary", used mainly in biology in phrases such as:

Coccobacillus

A coccobacillus is a type of bacterium with a shape intermediate between cocci and bacilli. Coccobacilli, then, are very short rods which may be mistaken for cocci.

Flagellum part of a cell of some organisms

A flagellum is a lash-like appendage that protrudes from the cell body of certain bacteria and eukaryotic cells termed as flagellates. A flagellate can have one or several flagella. The primary function of a flagellum is that of locomotion, but it also often functions as a sensory organelle, being sensitive to chemicals and temperatures outside the cell. The similar structure in the archaea functions in the same way but is structurally different and has been termed the archaellum.

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. [1] 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. [10]

Pathogenesis

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.

Innate immune system

The innate immune system is one of the two main immunity strategies found in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and it is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms.

Macrophage type of white blood cell

Macrophages are a type of white blood cell, of the immune system, that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the type of proteins specific to healthy body cells on its surface in a process called phagocytosis.

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. [11] 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. [12] In addition, this furtive entry into macrophages does not affect the cell’s normal trafficking. [13] 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. [11]

Lipopolysaccharide chemical compound

Lipopolysaccharides (LPS), also known as lipoglycans and endotoxins, are large molecules consisting of a lipid and a polysaccharide composed of O-antigen, outer core and inner core joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria.

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 cell membrane around a microorganism, a senescent cell or an apoptotic cell. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes. The lysosomes contain hydrolytic enzymes and reactive oxygen species (ROS) which kill and digest the pathogens. Phagosomes can also form in non-professional phagocytes, but they can only engulf a smaller range of particles, and do not contain ROS. The useful materials from the digested particles are moved into the cytosol, and waste is removed by exocytosis. Phagosome formation is crucial for tissue homeostasis and both innate and adaptive host defense against pathogens.

Apoptosis programmed cell death process

Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and global mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between the ages of 8 to 14 year old approximately 20 to 30 billion cells die per day.

Once inside macrophages, B. suis is able to endure the rapid acidificiation in the phagosome to pH 4.0-4.5 [14] by expressing metabolism genes mainly for amino acid synthesis. [13] The acidic pH is actually essential for replication of the bacteria by inducing major virulence genes of the virB operon [15] and the synthesis of DnaK chaperones. [14] DnaK is part of the heat shock protein 70 family, and aids in the correct synthesis and activation of certain virulence factors. [13]

In addition, the B. suis gene for nickel transport, nikA, is activated by metal ion deficiency and is expressed once in the phagosome. [16] Nickel is essential for many enzymatic reactions, including ureolysis to produce ammonia which in turn may neutralize acidic pH. [13] Since B. suis is unable to grow in a strongly acidic medium, it could be protected from acidification by the ammonia.

Summary:

Symptoms

The most frequent clinical sign following B. suis infection is abortion in pregnant females, reduced milk production, and infertility. [17] 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. [17] [18]

Swine also develop orchitis (swelling of the testicles), lameness (movement disability), hind limb paralysis, or spondylitis (inflammation in joints). [18]

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. [18] The only effective way to control and eradicate zoonosis is by vaccination of all susceptible hosts and elimination of infected animals. [19] The Brucella abortus (rough LPS Brucella) vaccine, developed for bovine brucellosis 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. [20]

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. [21] It is, however, considered to be one of the agents of lesser threat because many infections are asymptomatic and the mortality is low, [22] but it is used more as an incapacitating agent.

Related Research Articles

Phagocyte Cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells

Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are essential for fighting infections and for subsequent immunity. Phagocytes are important throughout the animal kingdom and are highly developed within vertebrates. One litre of human blood contains about six billion phagocytes. They were discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae. Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery. Phagocytes occur in many species; some amoebae behave like macrophage phagocytes, which suggests that phagocytes appeared early in the evolution of life.

Cryptococcus neoformans species of fungus

Cryptococcus neoformans is an encapsulated yeast and an obligate aerobe that can live in both plants and animals. Its teleomorph is Filobasidiella neoformans, a filamentous fungus belonging to the class Tremellomycetes. It is often found in bird excrement. Cryptococcus neoformans is an encapsulated fungal organism and it can cause disease in apparently immunocompetent, as well as immunocompromised, hosts.

<i>Francisella tularensis</i> species of bacterium

Francisella tularensis is a pathogenic species of Gram-negative coccobacillus, an aerobic bacterium. It is nonspore-forming, nonmotile, and the causative agent of tularemia, the pneumonic form of which is often lethal without treatment. It is a fastidious, facultative intracellular bacterium, which requires cysteine for growth. Due to its low infectious dose, ease of spread by aerosol, and high virulence, F. tularensis is classified as a Tier 1 Select Agent by the U.S. government, along with other potential agents of bioterrorism such as Yersinia pestis, Bacillus anthracis, and Ebola virus. When found in nature, Francisella tularensis can survive for several weeks at low temperatures in animal carcasses, soil, and water. In the laboratory, F. tularensis appears as small rods, and is grown best at 35-37°C.

<i>Chlamydia psittaci</i> species of bacterium

Chlamydia psittaci is a lethal intracellular bacterial species that may cause endemic avian chlamydiosis, epizootic outbreaks in mammals, and respiratory psittacosis in humans. Potential hosts include feral birds and domesticated poultry, as well as cattle, pigs, sheep, and horses. C. psittaci is transmitted by inhalation, contact, or ingestion among birds and to mammals. Psittacosis in birds and in humans often starts with flu-like symptoms and becomes a life-threatening pneumonia. Many strains remain quiescent in birds until activated by stress. Birds are excellent, highly mobile vectors for the distribution of chlamydia infection, because they feed on, and have access to, the detritus of infected animals of all sorts.

<i>Brucella</i> genus of bacteria

Brucella is a genus of Gram-negative bacteria, named after David Bruce (1855–1931). They are small, nonencapsulated, nonmotile, facultatively intracellular coccobacilli.

<i>Brucella melitensis</i> species of bacterium

Brucella melitensis is a Gram-negative coccobacillus bacterium from the Brucellaceae family. The bacterium causes ovine brucellosis, along with Brucella ovis. It can infect sheep, cattle, and sometimes humans, and it can be transmitted by the stable fly. It is zoonotic, unlike B. ovis, causing Malta fever or localized brucellosis in humans.

Intracellular parasites are microparasites that are capable of growing and reproducing inside the cells of a host. Some parasites can cause disease.

Bernhard Bang Danish veterinarian

Bernhard Lauritz Frederik Bang, was a Danish veterinarian. He discovered Brucella abortus in 1897, which came to be known as Bang's bacillus. Bang's bacillus was the cause of the contagious Bang's disease which can cause pregnant cattle to abort, and causes undulant fever in humans.

Brucella abortus is a Gram-negative proteobacterium in the family Brucellaceae and is one of the causative agents of brucellosis. The rod-shaped pathogen is classified under the domain Bacteria. The prokaryotic B. abortus is non-spore-forming, nonmotile and aerobic.

Phagolysosome A membrane-bounded intracellular vesicle formed by maturation of an early phagosome following the ingestion of particulate material by phagocytosis; during maturation, phagosomes acquire markers of late endosomes and lysosomes.

In biology, a phagolysosome, or endolysosome, is a cytoplasmic body formed by the fusion of a phagosome with a lysosome in a process that occurs during phagocytosis. Formation of phagolysosomes is essential for the intracellular destruction of microorganisms and pathogens. It takes place when the phagosome's and lysosome's membranes 'collide', at which point the lysosomal contents—including hydrolytic enzymes—are discharged into the phagosome in an explosive manner and digest the particles that the phagosome had ingested. Some products of the digestion are useful materials and are moved into the cytoplasm; others are exported by exocytosis.

Listeriolysin O (LLO) is a hemolysin produced by the bacterium Listeria monocytogenes, the pathogen responsible for causing listeriosis. The toxin may be considered a virulence factor, since it is crucial for the virulence of L. monocytogenes.

<i>Rhodococcus equi</i> species of bacterium

Rhodococcus equi is a Gram-positive coccobacillus bacterium. The organism is commonly found in dry and dusty soil and can be important for diseases of domesticated animals. The frequency of infection can reach near 60%. R. equi is an important pathogen causing pneumonia in foals. Since 2008, R. equi has been known to infect wild boar and domestic pigs. R. equi can infect humans. At-risk groups are immunocompromised people, such as HIV-AIDS patients or transplant recipients. Rhodococcus infection in these patients resemble clinical and pathological signs of pulmonary tuberculosis. It is facultative intracellular.

The alpha-D-phosphohexomutases are a large superfamily of enzymes, with members in all three domains of life. Enzymes from this superfamily are ubiquitous in organisms from E. Coli to humans, and catalyze a phosphoryl transfer reaction on a phosphosugar substrate. Four well studied subgroups in the superfamily are:

  1. Phosphoglucomutase (PGM)
  2. Phosphoglucomutase/Phosphomannomutase (PGM/PMM)
  3. Phosphoglucosamine mutase (PNGM)
  4. Phosphoaceytlglucosamine mutase (PAGM)

Actinobacillus pleuropneumoniae, is a Gram-negative, facultative anaerobic, respiratory pathogen found in pigs. It was first reported in 1957, and was formally declared to be the causative agent of porcine pleuropneumonia in 1964. It was reclassified in 1983 after DNA studies showed it was more closely related to A. lignieresii.

<i>Brucella ceti</i> species of bacterium

Brucella ceti is a gram negative bacterial pathogen of the Brucellaceae family that causes brucellosis in cetaceans. Brucella ceti has been found in both classes of cetaceans, mysticetes and odontocetes. Brucellosis in some dolphins and porpoises can result in serious clinical signs including fetal abortions, male infertility, neurobrucellosis, cardiopathies, bone and skin lesions, strand events, and death.

Brucella pinnipedialis is a species of bacteria. It causes infections and related diseases primarily in pinnipeds and cetaceans.

Vomocytosis

Vomocytosis is the cellular process by which live organisms that have previously been engulfed by a white blood cell are expelled without being destroyed. Vomocytosis was first reported in 2006 by two groups, working simultaneously in the UK and the USA, based on time-lapse microscopy footage characterising the interaction between macrophages and the human fungal pathogen Cryptococcus neoformans. Subsequently, this process has also been seen with other fungal pathogens such as Candida albicans and Candida krusei. It has also been speculated that the process may be related to the expulsion of bacterial pathogens such as Mycobacterium marinum from host cells. Vomocytosis has been observed in phagocytic cells from mice, humans and birds, as well as being directly observed in zebrafish and indirectly detected in mice. Amoebae exhibit a similar process to vomocytosis whereby phagosomal material that cannot be digested is exocytosed. Cryptococci are exocytosed from amoebae via this mechanism but inhibition of the constitutive pathway demonstrated that cryptococci could also be expelled via vomocytosis.

Bacterial small RNAs (sRNA) are an important class of regulatory molecules in bacteria such as Brucella. They are often bound to the chaperone protein Hfq, which allows them to interact with mRNA(s). In Brucella suis 1330 RNA sequencing identified a novel list of 33 sRNAs and 62 Hfq-associated mRNAs. In Brucella melitensis eight novel sRNA genes were identified using bioinformatic and experimental approach. One of them BSR0602 was found to modulate the intracellular survival of B. melitensis. In another large-scale deep sequencing study 1321 sRNAs were identified in B. melitensis. BSR0441 sRNA was further investigated in this study and shown to play role in the intracellular survival. sRNA BM-sr0117 from Brucella melitensis was identified and shown to be bound to and cleaved by Bm-RNase III. AbcR and AbcR2 were studied B. abortus. Seven novel sRNAs were validated and their interaction with a putative target sequence was verified in B. abortus.

References

  1. 1 2 Fretin, D; Whatmore, AM; Al Dahouk, S; Neubauer, H; Garin-Bastuji, B; Albert, D; Van Hessche, M; Ménart, M; Godfroid, J; Walravens, K; Wattiau, P (15 October 2008). "Brucella suis identification and biovar typing by real-time PCR". Veterinary Microbiology. 131 (3–4): 376–85. doi:10.1016/j.vetmic.2008.04.003. PMID   18499359.
  2. ↑ Godfroid, J; Cloeckaert, A; Liautard, JP; Kohler, S; Fretin, D; Walravens, K; Garin-Bastuji, B; Letesson, JJ (2005). "From the discovery of the Malta fever's agent to the discovery of a marine mammal reservoir, brucellosis has continuously been a re-emerging zoonosis". Veterinary Research. 36 (3): 313–26. doi:10.1051/vetres:2005003. PMID   15845228. Open Access logo PLoS transparent.svg
  3. ↑ Nicoletti, P (2016). "Brucellosis in Pigs - Reproductive System". Merck Veterinary Manual. Retrieved 2017-04-29.
  4. ↑ Wilson, G. S. (1955). Topley and Wilson’s principles of bacteriology and immunity. London, England: Edward Arnold Publishers Ltd.
  5. ↑ Halling, SM; Peterson-Burch, BD; Bricker, BJ; Zuerner, RL; Qing, Z; Li, LL; Kapur, V; Alt, DP; Olsen, SC (April 2005). "Completion of the genome sequence of Brucella abortus and comparison to the highly similar genomes of Brucella melitensis and Brucella suis". Journal of Bacteriology. 187 (8): 2715–26. doi:10.1128/jb.187.8.2715-2726.2005. PMC   1070361 . PMID   15805518.
  6. 1 2 3 Liautard, JP; Gross, A; Dornand, J; Köhler, S (June 1996). "Interactions between professional phagocytes and Brucella spp". Microbiología. 12 (2): 197–206. PMID   8767704.
  7. ↑ DelVecchio, VG; Kapatral, V; Elzer, P; Patra, G; Mujer, CV (20 December 2002). "The genome of Brucella melitensis". Veterinary Microbiology. 90 (1–4): 587–92. doi:10.1016/S0378-1135(02)00238-9. PMID   12414174.
  8. ↑ Moreno, E; Moriyon, I (8 January 2002). "Brucella melitensis: a nasty bug with hidden credentials for virulence". Proceedings of the National Academy of Sciences of the United States of America. 99 (1): 1–3. doi:10.1073/pnas.022622699. PMC   117501 . PMID   11782541.
  9. ↑ Fretin, D; Fauconnier, A; Köhler, S; Halling, S; Léonard, S; Nijskens, C; Ferooz, J; Lestrate, P; Delrue, RM; Danese, I; Vandenhaute, J; Tibor, A; DeBolle, X; Letesson, JJ (May 2005). "The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection". Cellular Microbiology. 7 (5): 687–98. doi:10.1111/j.1462-5822.2005.00502.x. PMID   15839898.
  10. ↑ Lagier, A; Brown, S; Soualah, A; Julier, I; Tourrand, B; Albert, D; Reyes, J; Garin-Bastuji, B (2005). "Brucellose aiguë à Brucella suis biovar 2 chez un chasseur de sanglier". Médecine et Maladies Infectieuses (in French). 35: 185.
  11. 1 2 Seleem, MN; Boyle, SM; Sriranganathan, N (25 May 2008). "Brucella: a pathogen without classic virulence genes". Veterinary Microbiology. 129 (1–2): 1–14. doi:10.1016/j.vetmic.2007.11.023. PMID   18226477.
  12. ↑ Lapaque, N., Moriyon, I., Moreno, E., Gorvel, J.P. "Brucella lipopolysaccharide acts as a virulence factor." Curr. Opin. Microbio 8 (2005): 60-66.
  13. 1 2 3 4 Köhler, S; Porte, F; Jubier-Maurin, V; Ouahrani-Bettache, S; Teyssier, J; Liautard, JP (20 December 2002). "The intramacrophagic environment of Brucella suis and bacterial response". Veterinary Microbiology. 90 (1–4): 299–309. doi:10.1016/S0378-1135(02)00215-8. PMID   12414150.
  14. 1 2 Porte, F; Liautard, JP; Köhler, S (August 1999). "Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages". Infection and Immunity. 67 (8): 4041–7. PMC   96697 . PMID   10417172.
  15. ↑ Boschiroli, ML; Ouahrani-Bettache, S; Foulongne, V; Michaux-Charachon, S; Bourg, G; Allardet-Servent, A; Cazevieille, C; Liautard, JP; Ramuz, M; O'Callaghan, D (5 February 2002). "The Brucella suis virB operon is induced intracellularly in macrophages". Proceedings of the National Academy of Sciences of the United States of America. 99 (3): 1544–9. doi:10.1073/pnas.032514299. PMC   122227 . PMID   11830669.
  16. ↑ Jubier-Maurin, V; Rodrigue, A; Ouahrani-Bettache, S; Layssac, M; Mandrand-Berthelot, MA; Köhler, S; Liautard, JP (January 2001). "Identification of the nik gene cluster of Brucella suis: regulation and contribution to urease activity". Journal of Bacteriology. 183 (2): 426–34. doi:10.1128/jb.183.2.426-434.2001. PMC   94896 . PMID   11133934.
  17. 1 2 Acha, PN; Szyfres, B, eds. (2003). "Brucellosis" (PDF). Zoonoses and communicable diseases common to man and animals. Volume 1 (3rd ed.). Washington, DC: Pan American Health Organization. pp. 40–66. ISBN   978-9275119914.
  18. 1 2 3 Seleem, MN; Boyle, SM; Sriranganathan, N (27 January 2010). "Brucellosis: a re-emerging zoonosis". Veterinary Microbiology. 140 (3–4): 392–8. doi:10.1016/j.vetmic.2009.06.021. PMID   19604656.
  19. ↑ Briones, G., N. Inon de Iannino, M. Roset, A. Vigliocco, P.S. Paulo and R.A. Ugalde. "Brucella abortus cyclic beta-1,2-glucan mutants have reduced virulence in mice and are defective in intracellular replication in HeLa cells." Infectious immunity 69 (2001): 4528-4535.
  20. ↑ Kemp, Jeffrey M. and Miller, Lowell A. "Oral vaccination and immunocontraception of feral swine using brucella suis with multimeric gnrh protein expression." Proc. 23rd vertebr. Pest Conf. (2008): 250-252.
  21. ↑ Christopher, G. W., Again, M. B., Cieslak, T. J. and Olson, P.E. "History of U. S. military contributions to the study of bacterial zoonoses." Military Medicine 170 (2005): 39-48.
  22. ↑ 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.
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