Bordetella (//) is a genus of small (0.2 – 0.7 µm), gram-negative coccobacilli of the phylum Proteobacteria. Bordetella species, with the exception of B. petrii, are obligate aerobes, as well as highly fastidious, or difficult to culture. All species can infect humans. The first three species to be described (B. pertussis, B. parapertussis, B. bronchiseptica); are sometimes referred to as the 'classical species'. Two of these (B. bronchiseptica and B. pertussis) are also motile.
B. pertussis and occasionally B. parapertussis cause pertussis or whooping cough in humans, and some B. parapertussis strains can colonise sheep. B. bronchiseptica rarely infects healthy humans, though disease in immunocompromised patients has been reported. B. bronchiseptica causes several diseases in other mammals, including kennel cough and atrophic rhinitis in dogs and pigs, respectively. Other members of the genus cause similar diseases in other mammals, and in birds (B. hinzii, B. avium).
The genus Bordetella is named after Jules Bordet.
The three most common species of Bordetella are B. pertussis, B. parapertussis and B. bronchiseptica. These species are known to accumulate in the respiratory tracts of mammals. This is most commonly seen in human infants as a product of an illness known as whooping cough. The particular species responsible for this illness in B. pertussis, and can only be found in humans. Even with extensive vaccination research on B. pertussis, whooping cough is still considered endemic in many countries. Due to the fact B. pertussis is only found in humans and shows little genetic variation form the other Bordetella species, it is thought that it was derived from a common ancestor in recent years.
B. parapertussis can affect both humans and other mammals, primarily sheep. Similar to B. pertussis, it causes whooping cough in babies. Yet, when strains found in sheep are isolated there is a strong distinction between those found in humans. This suggested that the varying strains of this species evolved independently of one another, the one found in humans and the one found in sheep. With this particular distinction it means that there is little to no transmission between the two reservoirs.
The species B. bronchiseptica however has a broader host range. Meaning it causes similar symptoms in a wide range of animals, while only occasionally affecting humans. These symptoms often manifest as chronic and asymptomatic respiratory infections. B. bronchiseptica is a small, coccoid shape sized at approximately 0.5 µm. It has peritrichous flagella that enables it to be motile. On a petri dish, colonies of this species appear small, grayish-white, smooth, and shiny. B. bronchiseptica is gram-negative.
The most thoroughly studied of the Bordetella species are B. bronchiseptica, B. pertussis and B. parapertussis, and the pathogenesis of respiratory disease caused by these bacteria has been reviewed. Transmission occurs by direct contact, or via respiratory aerosol droplets, or fomites. Bacteria initially adhere to ciliated epithelial cells in the nasopharynx, and this interaction with epithelial cells is mediated by a series of protein adhesins. These include filamentous haemaglutinin, pertactin, fimbriae, and pertussis toxin (though expression of pertussis toxin is unique to B. pertussis). As well as assisting in adherence to epithelial cells, some of these are also involved in attachment to immune effector cells.
The initial catarrhal phase of infection produces symptoms similar to those of the common cold, and during this period, large numbers of bacteria can be recovered from the pharynx. Thereafter, the bacteria proliferate and spread further into the respiratory tract, where the secretion of toxins causes ciliostasis and facilitates the entry of bacteria to tracheal/bronchial ciliated cells. One of the first toxins to be expressed is tracheal cytotoxin, which is a disaccharide-tetrapeptide derived from peptidoglycan. Unlike most other Bordetella toxins, tracheal cytotoxin is expressed constitutively, being a normal product of the breakdown of the bacterial cell wall. Other bacteria recycle this molecule back into the cytoplasm, but in Bordetella and Neisseria gonorrhoeae, it is released into the environment. Tracheal cytotoxin itself is able to reproduce paralysis of the ciliary escalator, inhibition of DNA synthesis in epithelial cells and ultimately killing of the same. One of the most important of the regulated toxins is adenylate cyclase toxin, which aids in the evasion of innate immunity. The toxin is delivered to phagocytic immune cells upon contact. Immune cell functions are then inhibited in part by the resulting accumulation of cyclic AMP. Recently discovered activities of adenylate cyclase toxin, including transmembrane pore formation and stimulation of calcium influx, may also contribute to the intoxication of phagocytes.
The virulence factors identified in the bordetella are common to all three species. These include adhesins, such as filamentous hemagglutinin (FHA), pertactin, tracheal colonization factor and fimbriae, and toxins, such as adenylate cyclase-hemolysin, dermonecrotic toxin and tracheal cytotoxin. These factors are then expressed and regulated most often by environmental stimuli.
Regulation of virulence factor expressionEdit
The expression of many Bordetella adhesins and toxins is controlled by the two-component regulatory system BvgAS. Much of what is known about this regulatory system is based on work with B. bronchiseptica, but BvgAS is present in B. pertussis, B. parapertussis and B. bronchiseptica and is responsible for phase variation or phenotypic modulation.
BvgS is a plasma membrane-bound sensor kinase which responds to stimulation by phosphorylating a cytoplasmic helix-turn-helix-containing protein, BvgA. When phosphorylated, BvgA has increased affinity for specific binding sites in Bvg-activated promoter sequences and is able to promote transcription in in vitro assays.
Most of the toxins and adhesins under BvgAS control are expressed under Bvg+ conditions (high BvgA-Pi concentration). But there are also genes expressed solely in the Bvg− state, most notably the flagellin gene flaA. The regulation of Bvg repressed genes is mediated by the product of a 624-bp open reading frame downstream of bvgA, the so-called Bvg-activated repressor protein, BvgR. BvgR binds to a consensus sequence present within the coding sequences of at least some Bvg-repressed genes. Binding of this protein to the consensus sequence represents gene expression by reducing transcription.
It is not known what the physiological signals for BvgS are, but in vitro BvgAS can be inactivated by millimolar concentrations of magnesium sulfate or nicotinic acid, or by reduction of the incubation temperature to ≤ 26 °C.
The identification of a specific point mutation in the BvgS gene which locks B. bronchiseptica in an intermediate Bvg phase revealed a class of BvgAS-regulated genes that are exclusively transcribed under intermediate concentrations of BvgA-Pi. This intermediate (Bvgi) phenotype can be reproduced in wild-type B. bronchiseptica by growth of the bacteria in a medium containing intermediate concentrations of the BvgAS modulator, nicotinic acid. In these conditions, some, but not all of the virulence factors associated with the Bvg+ phase are expressed, suggesting this two-component regulatory system can give rise to a continuum of phenotypic states in response to the environment.
Kennel Cough in Canines and FelinesEdit
Bordetella bronchiseptica causes upper-respiratory inflammation in dogs and cats, which is commonly referred to as Kennel Cough. This cough is loud, honking, and highly contagious. It can spread through the air, droplets, and indirect or direct contact, making dogs living in close confinements more susceptible; hence the nickname “Kennel Cough”. Other symptoms may include sneezing, runny nose, lethargy, or fever (Burke). While not typically fatal, Kennel Cough can lead to fatal bronchopneumonia in puppies and kittens or chronic bronchitis in older or immunocompromised dogs and cats (Burke).
If you suspect your pet may have contracted Bordetella (Kennel Cough), talk to your veterinarian who can diagnose the illness and determine the right treatment plan for your pet. Typically, treatment for Bordetella includes bed rest, cough medicine, and possibly antibiotics to help kill the bacteria and prevent secondary infections (Burke). Depending on your pet’s specific needs, your veterinarian may recommend other treatments. Always listen to your licensed veterinarian.
The Bordetella vaccine is non-essential, but highly recommended for dogs especially if they will be coming in contact with other dogs, such as at dog parks, boarding facilities, dog shows, training classes, etc (Burke). In fact, it can be required at certain facilities for entry. The vaccine can also be given to cats, but it is less commonly done because infection appears to be uncommon in adult cats. However, it may be a good idea to vaccinate a kitten if it is in a high-risk environment (i.e. living with multiple other cats) (Gardiner).
The Bordetella vaccine specifically targets the genus and species Bordetella bronchiseptica, the species typically responsible for Kennel Cough. The vaccine introduces the bacteria to the body in order to develop an immunity. It is important to remember that the vaccine only protects against one species of Bordetella. Therefore, it is possible for a pet to become infected with another Bordetella species or contract kennel cough from another source such as the parainfluenza virus even after being vaccinated for B. bronchiseptica (Burke). The Bordetella vaccine is also only about 70% effective (Bryant).
There are 3 licensed ways to deliver the Bordetella vaccine to dogs: orally, intranasally, and subcutaneously (under the skin). The 2 former methods are administered using live bacteria, while the latter is done with a killed bacteria. A comparative study done in 2013 by the School of Veterinary Medicine in Madison, Wisconsin studied the effectiveness of these three methods by vaccinating beagle puppies. The 40 beagles were divided into four groups; a group to test each of the 3 methods, plus one control group which was not vaccinated. After 42 days, the dogs were exposed to Bordetella bronchiseptica. This study determined that the live intranasal Bordetella vaccine was more effective than the killed subcutaneous vaccine, and the live oral vaccine works equally as well as the live intranasal vaccine (Larson). 
How The Bordetella Vaccine WorksEdit
Dogs contain cilia in their respiratory passageways, just like humans, that collect the debris that gets stuck in the mucous layer of the throat. If a dog has the Bordetella vaccine, it can lower the risk of the dog developing the cough. When a dog gets the vaccine, the Bordetella organisms connect to the cilia and override the immune cells that would usually attack the bad bacteria. The Bordetella vaccine is given to dogs by injecting the vaccine under the skin or into the nose. The intranasal method is the most common way the vaccine is given because it can be given at three weeks old whereas a shot can only be given at four months old. The intranasal path is the most preferred method of giving the vaccine because kennel cough infects dogs through the nose (Bryant, 2009) and it has been proven to be more effective than the subcutaneous shot (Larson).
- "Bordetella". NCBI taxonomy. Bethesda, MD: National Center for Biotechnology Information. Retrieved 16 January 2019.
- Ryan KJ; Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 978-0-8385-8529-0.
- Hewlett, Erik L.; Damron, F. Heath; Wong, Ting; Fernandez, Julieta; Sisti, Federico; Zacca, Federico; Gonyar, Laura A.; Hoffman, Casandra L. (2019-06-25). «Bordetella pertussis Can Be Motile and Express Flagellum-Like Structures». mBio (en inglés) 10(3): e00787-19. ISSN 2150-7511. PMID 31088927 |pmid=incorrecto (ayuda). doi:10.1128/mBio.00787-19
- Bauwens J, Spach D, Schacker T, Mustafa M, Bowden R (1992). "Bordetella bronchiseptica pneumonia and bacteremia following bone marrow transplantation". J Clin Microbiol. 30 (9): 2474–5. PMC 265527. PMID 1401019.
- Hewlett E (1997). "Pertussis: current concepts of pathogenesis and prevention". Pediatr Infect Dis J. 16 (4 Suppl): S78–84. doi:10.1097/00006454-199704001-00002. PMID 9109161.
- Cotter PA, Miller JF (2001). Groisman EA (ed.). Bordetella. Principles of Bacterial Pathogenesis. Academic Press. pp. 619–674. doi:10.1016/B978-012304220-0/50014-5. ISBN 978-0-12-304220-0.
- Mattoo S, Cherry J (2005). "Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due to Bordetella pertussis and Other Bordetella Subspecies". Clin Microbiol Rev. 18 (2): 326–82. doi:10.1128/CMR.18.2.326-382.2005. PMC 1082800. PMID 15831828.
- Gray MC, Donato GM, Jones FR, Kim T, Hewlett EL (2004). "Newly secreted adenylate cyclase toxin is responsible for intoxication of target cells by Bordetella pertussis". Mol. Microbiol. 53 (6): 1709–19. doi:10.1111/j.1365-2958.2004.04227.x. PMID 15341649.
- Hewlett EL, Donato GM, Gray MC (2006). "Macrophage cytotoxicity produced by adenylate cyclase toxin from Bordetella pertussis: more than just making cyclic AMP!". Mol. Microbiol. 59 (2): 447–59. doi:10.1111/j.1365-2958.2005.04958.x. PMID 16390441.
- Fiser R, Masín J, Basler M, Krusek J, Spuláková V, Konopásek I, Sebo P (2007). "Third activity of Bordetella adenylate cyclase (AC) toxin-hemolysin. Membrane translocation of AC domain polypeptide promotes calcium influx into CD11b+ monocytes independently of the catalytic and hemolytic activities". J. Biol. Chem. 282 (5): 2808–20. doi:10.1074/jbc.M609979200. PMID 17148436.
- Uhl M, Miller J (1994). "Autophosphorylation and phosphotransfer in the Bordetella pertussis BvgAS signal transduction cascade". Proc Natl Acad Sci USA. 91 (3): 1163–7. Bibcode:1994PNAS...91.1163U. doi:10.1073/pnas.91.3.1163. PMC 521474. PMID 8302847.
- Steffen P, Goyard S, Ullmann A (1996). "Phosphorylated BvgA is sufficient for transcriptional activation of virulence-regulated genes in Bordetella pertussis". EMBO J. 15 (1): 102–9. doi:10.1002/j.1460-2075.1996.tb00338.x. PMC 449922. PMID 8598192.
- Akerley B, Monack D, Falkow S, Miller J (1992). "The bvgAS locus negatively controls motility and synthesis of flagella in Bordetella bronchiseptica". J Bacteriol. 174 (3): 980–90. doi:10.1128/jb.174.3.980-990.1992. PMC 206178. PMID 1370665.
- Merkel T, Stibitz S (1995). "Identification of a locus required for the regulation of bvg-repressed genes in Bordetella pertussis". J Bacteriol. 177 (10): 2727–36. doi:10.1128/jb.177.10.2727-2736.1995. PMC 176943. PMID 7751282.
- Beattie D, Mahan M, Mekalanos J (1993). "Repressor binding to a regulatory site in the DNA coding sequence is sufficient to confer transcriptional regulation of the vir-repressed genes (vrg genes) in Bordetella pertussis". J Bacteriol. 175 (2): 519–27. doi:10.1128/jb.175.2.519-527.1993. PMC 196167. PMID 8419298.
- Cotter P, Miller J (1997). "A mutation in the Bordetella bronchiseptica bvgS gene results in reduced virulence and increased resistance to starvation, and identifies a new class of Bvg-regulated antigens". Mol Microbiol. 24 (4): 671–85. doi:10.1046/j.1365-2958.1997.3821741.x. PMID 9194696.
- van den Akker W (1997). "Bordetella bronchiseptica has a BvgAS-controlled cytotoxic effect upon interaction with epithelial cells". FEMS Microbiol Lett. 156 (2): 239–44. doi:10.1016/S0378-1097(97)00431-X. PMID 9513272.
- "How Frequently Does A Dog Need A Bordetella Vaccine?". Cornerstone Animal Hospital. Retrieved 22 October 2020.
- Bryant, C. (2009, January 23). How Bordetella Vaccines Work. Retrieved November 18, 2020, from https://animals.howstuffworks.com/pets/pet-travel/bordetella-vaccine1.htm.
- Burke, A. (2018, July 13). 5 Facts About the Bordetella Vaccine for Dogs. Retrieved October 22, 2020, from https://www.akc.org/expert-advice/health/facts-bordetella-vaccine-dogs/
- Gardiner, J. (2020, August 11). Vaccination Guidelines for Dogs and Cats. Retrieved November 18, 2020, from https://healthtopics.vetmed.ucdavis.edu/health-topics/feline/vaccination-guidelines-dogs-and-cats
- Kadlec, K., & Schwarz, S. (2018). Antimicrobial Resistance in Bordetella bronchiseptica (1062719807 809797198 L. Cavaco & 1062719808 809797198 J. Shen, Eds.). Antimicrobial Resistance in Bacteria from Livestock and Companion Animals, 365-375. doi:10.1128/9781555819804.ch16
- Larson, Laurie & Thiel, Bliss & Sharp, Patricia & Schultz, Ronald. (2013). A Comparative Study of Protective Immunity Provided by Oral, Intranasal and Parenteral Canine Bordetella bronchiseptica Vaccines. International Journal of Applied Research in Veterinary Medicine. 11. 153-16