Bordetella

Taxobox
color = lightgrey
name = "Bordetella"

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image_width = 240px
image_caption = Flagellated "B. bronchiseptica"
regnum = Bacteria
phylum = Proteobacteria
classis = Beta Proteobacteria
ordo = Burkholderiales
familia = Alcaligenaceae
genus = "Bordetella"
genus_authority = Moreno-López 1952
subdivision_ranks = Species
subdivision ="'B. ansorpii'"
"B. avium"
"B. bronchiseptica"
"B. hinzii"
"B. holmesii"
"B. parapertussis"
"B. pertussis"
"B. petrii"
"B. trematum"

"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. Three species are human pathogens ("B. pertussis", "B. parapertussis", "B. bronchiseptica"); one of these ("B. bronchiseptica") is also motile.cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | id = ISBN 0838585299 ]

"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.cite journal |author=Bauwens J, Spach D, Schacker T, Mustafa M, Bowden R |title=Bordetella bronchiseptica pneumonia and bacteremia following bone marrow transplantation |journal=J Clin Microbiol |volume=30 |issue=9 |pages=2474–5 |year=1992 |pmid=1401019] "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.

Pathogenesis of "Bordetella" infections

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 reviewedcite journal |author=Hewlett E |title=Pertussis: current concepts of pathogenesis and prevention |journal=Pediatr Infect Dis J |volume=16 |issue=4 Suppl |pages=S78–84 |year=1997 |pmid=9109161 |doi=10.1097/00006454-199704001-00002] .cite book | author = Cotter PA, Miller JF | title = Bordetella "in:" Principles of Bacterial Pathogenesis (Groisman EA, ed.) | pages = pp. 620-85 | publisher = Academic Press | year = 2000 | id = ISBN 0123042208 ] cite journal |author=Mattoo S, Cherry J |title=Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies |journal=Clin Microbiol Rev |volume=18 |issue=2 |pages=326–82 |year=2005 |pmid=15831828 |doi=10.1128/CMR.18.2.326-382.2005] 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.cite journal |author=Gray MC, Donato GM, Jones FR, Kim T, Hewlett EL |title=Newly secreted adenylate cyclase toxin is responsible for intoxication of target cells by Bordetella pertussis |journal=Mol. Microbiol. |volume=53 |issue=6 |pages=1709–19 |year=2004 |pmid=15341649 |doi=10.1111/j.1365-2958.2004.04227.x] 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.cite journal |author=Hewlett EL, Donato GM, Gray MC |title=Macrophage cytotoxicity produced by adenylate cyclase toxin from Bordetella pertussis: more than just making cyclic AMP! |journal=Mol. Microbiol. |volume=59 |issue=2 |pages=447–59 |year=2006 |pmid=16390441 |doi=10.1111/j.1365-2958.2005.04958.x] cite journal |author=Fiser R, Masín J, Basler M, Krusek J, Spuláková V, Konopásek I, Sebo P |title=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 |journal=J. Biol. Chem. |volume=282 |issue=5 |pages=2808–20 |year=2007 |pmid=17148436 |doi=10.1074/jbc.M609979200]

making of virulence factor expression in Bordetella

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.cite journal |author=Uhl M, Miller J |title=Autophosphorylation and phosphotransfer in the Bordetella pertussis BvgAS signal transduction cascade |journal=Proc Natl Acad Sci U S A |volume=91 |issue=3 |pages=1163–7 |year=1994 |pmid=8302847 |doi=10.1073/pnas.91.3.1163] cite journal |author=Steffen P, Goyard S, Ullmann A |title=Phosphorylated BvgA is sufficient for transcriptional activation of virulence-regulated genes in Bordetella pertussis |journal=EMBO J |volume=15 |issue=1 |pages=102–9 |year=1996 |pmid=8598192]

Most of the toxins and adhesins under BvgAS control are expressed under Bvg⁺ conditions (high BvgA-P_i concentration). But there are also genes expressed solely in the Bvg^- state, most notably the flagellin gene "flaA".cite journal |author=Akerley B, Monack D, Falkow S, Miller J |title=The bvgAS locus negatively controls motility and synthesis of flagella in Bordetella bronchiseptica |journal=J Bacteriol |volume=174 |issue=3 |pages=980–90 |year=1992 |pmid=1370665] 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.cite journal |author=Merkel T, Stibitz S |title=Identification of a locus required for the regulation of bvg-repressed genes in Bordetella pertussis |journal=J Bacteriol |volume=177 |issue=10 |pages=2727–36 |year=1995 |pmid=7751282] 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.cite journal |author=Beattie D, Mahan M, Mekalanos J |title=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 |journal=J Bacteriol |volume=175 |issue=2 |pages=519–27 |year=1993 |pmid=8419298]

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.cite journal |author=Cotter P, Miller J |title=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 |journal=Mol Microbiol |volume=24 |issue=4 |pages=671–85 |year=1997 |pmid=9194696 |doi=10.1046/j.1365-2958.1997.3821741.x] cite journal |author=van den Akker W |title=Bordetella bronchiseptica has a BvgAS-controlled cytotoxic effect upon interaction with epithelial cells |journal=FEMS Microbiol Lett |volume=156 |issue=2 |pages=239–44 |year=1997 |pmid=9513272 |doi=10.1016/S0378-1097(97)00431-X] !

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-P_i. This intermediate (Bvg_i) 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.

References