Bordetella

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Bordetella
Bordetella bronchiseptica 02.jpg
Flagellated Bordetella bronchiseptica
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Bacteria
Phylum: Pseudomonadota
Class: Betaproteobacteria
Order: Burkholderiales
Family: Alcaligenaceae
Genus: Bordetella
Moreno-López 1952
Species [1]

Bordetella ( /ˌbɔːrdəˈtɛlə/ ) is a genus of small (0.2 – 0.7 μm), Gram-negative, coccobacilli bacteria of the phylum Pseudomonadota. 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. pertussis and B. bronchiseptica) are also motile. [3] [4]

Contents

There are about 16 different species of Bordetella likely descending from ancestors who lived in soil and/or water environments. [5] B. pertussis and occasionally B. parapertussis cause pertussis (whooping cough) in humans, and some B. parapertussis strains only colonize sheep. [5] It has also been known to cause bronchitis in cats and bronchopneumonia in pigs. [5]

B. bronchiseptica rarely infects healthy humans, though disease in immunocompromised patients has been reported. [6] B. bronchiseptica causes several diseases in other mammals, including kennel cough in dogs and atrophic rhinitis in pigs. 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.

Pathogenesis

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 is 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 from 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 suggests 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 (gram-negative, aerobic) however has a broader host range, causing 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, coccobacillus 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. This species is also typically associated with kennel cough (Canine Respiratory Infectious Disease (CRID)) in dogs. [7] [8]

Molecular structure of pertussis toxin complex (protein) highlighting alpha helices and beta pleated sheets. Also including the 5 different sub-units. Pertussin toxin.png
Molecular structure of pertussis toxin complex (protein) highlighting alpha helices and beta pleated sheets. Also including the 5 different sub-units.

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. [9] [10] [11] Transmission occurs by direct contact, 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. [12] 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.

Virulence factors

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. Differences in virulence factors relate to the loss of regulatory or control functions. Bordetella sp. is typically found to live within the hosts' respiratory tract and immune system and can transmit to new hosts. [5] Bordetella pertussis also affects human adults and even with an 85% vaccination coverage over 160,000 related deaths occur each year all around the globe. [5] There are few antimicrobial susceptibility testing methods but no change or progress have been discovered as of 2018. [5] Most studies performed using Bordetella vaccines have many flaws and fail to come to an official conclusion.

Regulation of virulence factor expression

The expression of many Bordetella adhesins and toxins is controlled by the two-component regulatory system BvgAS. [10] [11] 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. [13] [14]

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. [15] 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. [16] 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. [17]

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. [18] [19]

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. [18]

Vaccines

The Bordetella vaccine is non-essential, but highly recommended for dogs especially if they are expected to come into contact with other dogs at dog parks, boarding facilities, dog shows, training classes, etc. [20] 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). [21]

The Bordetella vaccine specifically targets Bordetella bronchiseptica, the species typically responsible for kennel cough. The vaccine introduces the bacteria (live or dead) 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. [20] The Bordetella vaccine is also only about 70% effective. [22]

There are three licensed ways to deliver the Bordetella vaccine to dogs: orally, intranasally, and subcutaneously. The two 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 three methods, plus one unvaccinated control group. 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. [23]

Related Research Articles

<span class="mw-page-title-main">Whooping cough</span> Human disease caused by the bacteria Bordetella pertussis

Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious, vaccine-preventable bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by two or three months of severe coughing fits. Following a fit of coughing, a high-pitched whoop sound or gasp may occur as the person breathes in. The violent coughing may last for 10 or more weeks, hence the phrase "100-day cough". The cough may be so hard that it causes vomiting, rib fractures, and fatigue. Children less than one year old may have little or no cough and instead have periods when they cannot breathe. The incubation period is usually seven to ten days. Disease may occur in those who have been vaccinated, but symptoms are typically milder.

<span class="mw-page-title-main">Exotoxin</span> Toxin from bacteria that destroys or disrupts cells

An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.

<i>Bordetella bronchiseptica</i> Species of bacterium

Bordetella bronchiseptica is a small, gram-negative, rod-shaped bacterium of the genus Bordetella. It can cause infectious bronchitis in dogs and other animals, but rarely infects humans. Closely related to B. pertussis—the obligate human pathogen that causes pertussis ; B. bronchiseptica can persist in the environment for extended periods.

<span class="mw-page-title-main">Pertactin</span> Virulence factor of Bordetella pertussis

In molecular biology, pertactin (PRN) is a highly immunogenic virulence factor of Bordetella pertussis, the bacterium that causes pertussis. Specifically, it is an outer membrane protein that promotes adhesion to tracheal epithelial cells. PRN is purified from Bordetella pertussis and is used for the vaccine production as one of the important components of acellular pertussis vaccine.

<i>Corynebacterium diphtheriae</i> Species of prokaryote

Corynebacterium diphtheriae is a Gram-positive pathogenic bacterium that causes diphtheria. It is also known as the Klebs–Löffler bacillus because it was discovered in 1884 by German bacteriologists Edwin Klebs (1834–1912) and Friedrich Löffler (1852–1915). The bacteria are usually harmless unless they are infected by a bacteriophage that carries a gene that gives rise to a toxin. This toxin causes the disease. Diphtheria is caused by the adhesion and infiltration of the bacteria into the mucosal layers of the body, primarily affecting the respiratory tract and the subsequent release of an exotoxin. The toxin has a localized effect on skin lesions, as well as a metastatic, proteolytic effects on other organ systems in severe infections. Originally a major cause of childhood mortality, diphtheria has been almost entirely eradicated due to the vigorous administration of the diphtheria vaccination in the 1910s.

<span class="mw-page-title-main">Kennel cough</span> Upper respiratory infection affecting dogs

Kennel cough is an upper respiratory infection affecting dogs. There are multiple causative agents, the most common being the bacterium Bordetella bronchiseptica, followed by canine parainfluenza virus, and to a lesser extent canine coronavirus. It is highly contagious; however, adult dogs may display immunity to reinfection even under constant exposure. Kennel cough is so named because the infection can spread quickly among dogs in the close quarters of a kennel or animal shelter.

Bacterial adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually in the host they are infecting or living in. Adhesins are a type of virulence factor.

<span class="mw-page-title-main">Pertussis toxin</span> Group of toxins

Pertussis toxin (PT) is a protein-based AB5-type exotoxin produced by the bacterium Bordetella pertussis, which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection. Research suggests PT may have a therapeutic role in treating a number of common human ailments, including hypertension, viral infection, and autoimmunity.

<i>Bordetella pertussis</i> Species of bacterium causing pertussis or whooping cough

Bordetella pertussis is a Gram-negative, aerobic, pathogenic, encapsulated coccobacillus bacterium of the genus Bordetella, and the causative agent of pertussis or whooping cough. Its virulence factors include pertussis toxin, adenylate cyclase toxin, filamentous haemagglutinin, pertactin, fimbria, and tracheal cytotoxin.

Adenylate cyclase toxin is a virulence factor produced by some members of the genus Bordetella. Together with the pertussis toxin it is the most important virulence factor of the causative agent of whooping cough, Bordetella pertussis. Bordetella bronchiseptica and Bordetella parapertussis, also able to cause pertussis-like symptoms, also produce adenylate cyclase toxin. It is a toxin secreted by the bacteria to influence the host immune system.

<i>Bordetella parapertussis</i> Species of bacterium

Bordetella parapertussis is a small Gram-negative bacterium of the genus Bordetella that is adapted to colonise the mammalian respiratory tract. Pertussis caused by B. parapertussis manifests with similar symptoms to B. pertussis-derived disease, but in general tends to be less severe. Immunity derived from B. pertussis does not protect against infection by B. parapertussis, however, because the O-antigen is found only on B. parapertussis. This antigen protects B. parapertussis against antibodies specific to B. pertussis, so the bacteria are free to colonize the host's lungs without being subject to attack by previous antibodies. These findings suggest B. parapertussis evolved in a host population that had already developed immunity to B. pertussis, where being able to evade B. pertussis immunity was an advantage.

The AB5 toxins are six-component protein complexes secreted by certain pathogenic bacteria known to cause human diseases such as cholera, dysentery, and hemolytic–uremic syndrome. One component is known as the A subunit, and the remaining five components are B subunits. All of these toxins share a similar structure and mechanism for entering targeted host cells. The B subunit is responsible for binding to receptors to open up a pathway for the A subunit to enter the cell. The A subunit is then able to use its catalytic machinery to take over the host cell's regular functions.

Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.

The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein sequences, and extracellular secretion by the type I secretion systems (T1SS). The name RTX refers to the glycine and aspartate-rich repeats located at the C-terminus of the toxin proteins, which facilitate export by a dedicated T1SS encoded within the rtx operon.

Adenylate cyclase toxin (CyaA) is released from bacterium Bordetella pertussis by the T1SS and released in the host’s respiratory tract in order to suppress its early innate and subsequent adaptive immune defense.

<span class="mw-page-title-main">Tracheal cytotoxin</span> Chemical compound

Tracheal cytotoxin (TCT) is a 921 dalton glycopeptide released by Bordetella pertussis, Vibrio fischeri, and Neisseria gonorrhoeae. It is a soluble piece of peptidoglycan (PGN) found in the cell wall of all gram-negative bacteria, but only some bacteria species release TCT due to inability to recycle this piece of anhydromuropeptide.

Bordetella avium is a gram negative, nonfermentative, strictly aerobic, motile bacterium from the genus Bordetella which has been isolated from patients with respiratory disease. B. avium has a global distribution, that mainly affects young domesticated turkeys. The disease in birds is called bordetellosis, and is largely associated with confined spaces and multi-aged flocks where management practices are sub optimal. In most infections, mortality is typically low but morbidity is very high.

Bordetella trematum is a species of Gram-negative bacteria identified in 1996 by comparison of 10 strains of B. trematum against other well characterized Bordetella and Alcaligenes species. The term trema refers to something pierced or penetrated, or to a gap. "Trematum" pertains to open things, and refers to the presence of bacteria in wounds and other exposed parts of the body. Strain LMG 13506T is the reference strain for this species.

Vaccine resistance is the evolutionary adaptation of pathogens to infect and spread through vaccinated individuals, analogous to antimicrobial resistance. It concerns both human and animal vaccines. Although the emergence of a number of vaccine resistant pathogens has been well documented, this phenomenon is nevertheless much more rare and less of a concern than antimicrobial resistance.

Whole-cell vaccines are a type of vaccine that has been prepared in the laboratory from entire cells. Such vaccines simultaneously contain multiple antigens to activate the immune system. They induce antigen-specific T-cell responses.

References

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  2. ↑ Tran TD, Ali MA, Lee D, Félix MA, Luallen RJ (4 February 2022). "Bacterial filamentation as a mechanism for cell-to-cell spread within an animal host". Nature Communications. 13 (1): 693. Bibcode:2022NatCo..13..693T. doi:10.1038/s41467-022-28297-6. PMC   8816909 . PMID   35121734.
  3. ↑ Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN   978-0-8385-8529-0.
  4. ↑ Hoffman CL, Gonyar LA, Zacca F, Sisti F, Fernandez J, Wong T, Damron FH, Hewlett EL (2019-06-25). "Bordetella pertussis Can Be Motile and Express Flagellum-Like Structures". mBio. 10 (3). American Society for Microbiology: e00787-19. doi:10.1128/mbio.00787-19. ISSN   2161-2129. PMC   6520453 . PMID   31088927.
  5. 1 2 3 4 5 6 Kamanova J (2020). "Bordetella Type III Secretion Injectosome and Effector Proteins". Frontiers in Cellular and Infection Microbiology. 10: 466. doi: 10.3389/fcimb.2020.00466 . ISSN   2235-2988. PMC   7498569 . PMID   33014891.
  6. ↑ 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): 2474–75. doi:10.1128/jcm.30.9.2474-2475.1992. PMC   265527 . PMID   1401019.
  7. ↑ Fastrès A, Canonne MA, Taminiau B, Billen F, Garigliany MM, Daube G, Clercx C (2020-03-24). "Analysis of the lung microbiota in dogs with Bordetella bronchiseptica infection and correlation with culture and quantitative polymerase chain reaction". Veterinary Research. 51 (1): 46. doi: 10.1186/s13567-020-00769-x . ISSN   1297-9716. PMC   7092585 . PMID   32209128.
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  12. ↑ 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. S2CID   22884606.
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  19. ↑ 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:10.1111/j.1574-6968.1997.tb12734.x. PMID   9513272.
  20. 1 2 Burke A (May 26, 2017). "5 Facts About the Bordetella Vaccine for Dogs". American Kennel Club. Retrieved 2023-04-21.
  21. ↑ Gardiner J (2019-03-27). "Vaccination Guidelines for Dogs and Cats". Animal Health Topics / School of Veterinary Medicine. Retrieved 2023-04-21.
  22. ↑ "How Bordetella Vaccines Work". HowStuffWorks. 2009-01-23. Retrieved 2023-04-21.
  23. ↑ 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. 153–160.

[1] [2] [3] [4] [5]

  1. ↑ Bryant, C. (2009, January 23). How Bordetella Vaccines Work. Retrieved November 18, 2020, from https://animals.howstuffworks.com/pets/pet-travel/bordetella-vaccine1.htm.
  2. ↑ 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/
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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. 153–160
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