Bordetella
Encyclopedia
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 aerobe
s as well as highly fastidious, or difficult to culture. Three species are human pathogen
s (B. pertussis
, B. parapertussis
, B. bronchiseptica
); one of these (B. bronchiseptica) is 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 Bordetella genus is named after Jules Bordet
.
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 catarrh
al 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.
modulation.
BvgS is a plasma membrane-bound sensor kinase
which responds to stimulation by phosphorylating
a cytoplasm
ic 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 represses 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 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 that this two component regulatory system can give rise to a continuum of phenotypic states in response to the environment.
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
of small (0.2 - 0.7 µm), Gram-negative
Gram-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...
coccobacilli of the phylum proteobacteria
Proteobacteria
The Proteobacteria are a major group of bacteria. They include a wide variety of pathogens, such as Escherichia, Salmonella, Vibrio, Helicobacter, and many other notable genera....
. Bordetella species, with the exception of B. petrii, are obligate aerobe
Obligate aerobe
An obligate aerobe is an aerobic organism that requires oxygen to grow. Through cellular respiration, these organisms use oxygen to oxidize substances, like sugars or fats, in order to obtain energy. During respiration, they use oxygen as the terminal electron acceptor...
s as well as highly fastidious, or difficult to culture. Three species are human pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s (B. pertussis
Bordetella pertussis
Bordetella pertussis is a Gram-negative, aerobic coccobacillus of the genus Bordetella, and the causative agent of pertussis or whooping cough. Unlike B. bronchiseptica, B. pertussis is non-motile. Its virulence factors include pertussis toxin, filamentous hæmagglutinin, pertactin, fimbria, and...
, B. parapertussis
Bordetella parapertussis
Bordetella parapertussis is a small Gram-negative bacterium of the genus Bordetella which is adapted to colonise the mammalian respiratory tract. Pertussis caused by B. parapertussis manifests with similar symptoms to B. pertussis-derived disease but tends to be generally less severe. Immunity...
, B. bronchiseptica
Bordetella bronchiseptica
Bordetella bronchiseptica is a small, gram-negative, rod-shaped bacterium of the genus Bordetella. It can cause infectious bronchitis, but rarely infects humans. Closely related to B. pertussis—the obligate human pathogen that causes pertussis or whooping cough—B...
); one of these (B. bronchiseptica) is also motile.
B. pertussis and occasionally B. parapertussis cause pertussis
Pertussis
Pertussis, also known as whooping cough , is a highly contagious bacterial disease caused by Bordetella pertussis. Symptoms are initially mild, and then develop into severe coughing fits, which produce the namesake high-pitched "whoop" sound in infected babies and children when they inhale air...
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
Kennel cough
Kennel cough is a highly contagious canine illness characterized by inflammation of the upper respiratory system. It can be caused by viral infections such as canine distemper, canine adenovirus, canine parainfluenza virus, or canine respiratory coronavirus, or bacterial infections such as...
and atrophic rhinitis
Atrophic rhinitis
Chronic atrophic rhinitis is a chronic inflammation of nose characterised by atrophy of nasal mucosa, including the glands, turbinate bones and the nerve elements supplying the nose. Chronic atrophic rhinitis may be primary and secondary...
in dogs and pigs, respectively. Other members of the genus cause similar diseases in other mammals, and in birds (B. hinzii, B. avium).
The Bordetella genus is named after Jules Bordet
Jules Bordet
Jules Jean Baptiste Vincent Bordet was a Belgian immunologist and microbiologist. The bacterial genus Bordetella is named after him.-Biography:Bordet was born at Soignies, Belgium...
.
Pathogenesis
The most often 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 epithelialEpithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
cells in the nasopharynx and this interaction with epithelial cells is mediated by a series of protein adhesins. These include filamentous haemaglutinin, pertactin
Pertactin
Pertactin is a highly immunogenic virulence factor of Bordetella pertussis, a 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...
, fimbriae, and pertussis toxin
Pertussis toxin
Pertussis toxin 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...
(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 catarrh
Catarrh
Catarrh is a disorder of inflammation of the mucous membranes in one of the airways or cavities of the body. It can result in a thick exudate of mucus and white blood cells caused by the swelling of the mucous membranes in the head in response to an infection...
al 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
Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...
. 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
Neisseria gonorrhoeae
Neisseria gonorrhoeae, also known as gonococci , or gonococcus , is a species of Gram-negative coffee bean-shaped diplococci bacteria responsible for the sexually transmitted infection gonorrhea.N...
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.
Regulation of virulence factor expression
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 phenotypicPhenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
modulation.
BvgS is a plasma membrane-bound sensor kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
which responds to stimulation by phosphorylating
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
a cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
ic helix-turn-helix
Helix-turn-helix
In proteins, the helix-turn-helix is a major structural motif capable of binding DNA. It is composed of two α helices joined by a short strand of amino acids and is found in many proteins that regulate gene expression...
-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
Flagellin
Flagellin is a protein that arranges itself in a hollow cylinder to form the filament in bacterial flagellum. It has a mass of about 30,000 to 60,000 daltons...
gene flaA. The regulation of Bvg repressed genes is mediated by the product of a 624-bp open reading frame
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...
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 represses gene expression by reducing transcription.
It is not known what the physiological signals for BvgS are, but in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
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 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 that this two component regulatory system can give rise to a continuum of phenotypic states in response to the environment.