BORDETELLA K.V.PRAVEEN CHANDER

Important species Bordetella pertussis - Bordet-Gengou bacillus Bordetella parapertussis Bordetlla bronchiseptica - ancestral form Bordetella avium -causes respiratory disease in turkeys

Virulence B. pertussis invades the human host through the inhalation of respiratory droplets and adheres to the ciliated epithelium of the respiratory tract (Babu et al., 2001). It was believed that B. pertussis was an entirely extracellular pathogen, but it has recently been shown that B. pertussis can invade aveolar macrophages. This pathogen can multiply rapidly on the mucosal membrane of the upper respiratory tract, producing adhesions that allow it to colonize by adhering to the ciliated epithelium (Babu et al., 2001). B. pertussis must survive within the hostile environment of its human host by producing a variety of virulence factors in an attempt to evade or counter the immune system of the host as it tries to clear the infection (Barnes et al., 2001). These virulence factors include adhesions such as filamentous hemagglutinin, agglutinogens, peractin, and fimbriae as well as a number of toxins including pertussis toxin, adenylate cyclase toxin, trachael cytotoxin, dermonecrotic toxin and heat-labile toxin (CDC, 2005). Like most Gram negative pathogens, B. pertussis also contains a lipopolysaccharide coat that acts as an endotoxin and can aid colonization by agglutinating human cells (Steele, 2004). Steele, R.W. Pertussis: Is Eradication Achievable. Pediatric Annals. Aug 2004. 33(8):525-534

Adhesions Filamentous hemagglutinin Pertactin Fimbriae Adherence to the ciliated epithelial cells and macrophages is very important in colonization of the respiratory tract (Babu et al., 2001). B. pertussis produces several virulence factors that allow the bacterium to bind to cells and colonize the host. Of these adhesions, filamentous hemagglutinin (FHA) is one of the most important. FHA is a filamentous structure that measures about 2 nm wide and 50 nm long (Babu et al., 2001). It is a large, hairpin shaped molecule that is highly immunogenic and is therefore a primary component in acellular pertussis vaccines (Mattoo et al., 2001). FHA secretion requires the presence of the outer membrane protein FhaC; in its absence, FHA will not be secreted and will instead be degraded within the cell (Mattoo et al., 2001). The opsonization of antibodies to FHA can actually decrease phagocytosis of FHA expressing B. pertussis and FHA can affect cell mediated immunity by inhibiting cytokine responses (Veal-Carr and Stibitz, 2005). FHA is thought to be the major colonizing factor for B. pertussis as it promotes attachment to the upper respiratory tract and the trachea (Steele, 2004). It has been found to be both necessary and sufficient by itself to mediate adherence to rat lung epithelium and is absolutely required for trachael colonization in healthy animals, but cannot be the lone factor in this colonization (Mattoo et al., 2001). Pertactin is a surface associated protein that undergoes autoproteolytic processing of its C-terminus (Mattoo et al., 2001). Pertactin is thought to play a role in attachment because all three pertactin proteins contain motifs commonly present on proteins that are responsible for protein-protein interactions in eukaryotic cell binding (Mattoo et al., 2001). Pertactin is expressed after FHA but before the pertussis and adenylate cyclase toxins during infection, further implicating it as a colonizing factor (Merkel et al., 1998). Purified pertactin has also been shown to cause Chinese Hamster Ovary (CHO) cells to bind to tissue culture wells and expression of pertactin in E. coli increases the bacterial adherence and invasiveness to mammalian cell lines (Mattoo et al., 2001). B. pertussis, like most Gram negative pathogens, express fimbriae on their cell surface and Bordetella predominantly expresses Fim2 and Fim3 serotypes (Mattoo et al., 2001). Fimbriae also serve to mediate attachment to the host epithelia during the important first steps in colonization, but it has been difficult to establish a definitive role for fimbriae in this process due to the expression of other adhesions and the difficulty in finding a proper animal model (Mattoo et al., 2001). Fimbriae, however, have been determined to bind sulfated sugars such as heparan sulfate, chondroitin sulfate, and dextran sulfate that are ubiquitously present throughout the mammalian respiratory tract. The fimbriae mimic fibronectin, a host protein found in the extracellular matrix that also exhibits these binding interactions. The two proteins share significant homology that allows the fimbriae to use host ligand-receptor interactions to further infection (Babu et al., 2001). Fimbriae are thought to be the cause of the persistency of B. pertussis infections (Babu et al., 2001) and Fimbriae have also been found to elicit a host immune response that is important in the prevention of superinfection (Mattoo et al., 2001). http://www.rivm.nl/infectieziektenbulletin/bul1306/kinkhoest.jpg http://www.my-pharm.ac.jp/~yishibas/research/Pertussis1.jpg

Toxins Pertussis Toxin Adenylate Cyclase Toxin Tracheal cytotoxin Dermonecrotic toxin Heat-labile toxin Whooping cough (Pertussis) is primarily a toxin mediated disease (CDC, 2005). After the bacterium adheres to the ciliated epithelium of the respiratory tract and colonizes the host, it secretes toxins that lead to the death of these epithelium cells, a decrease in ciliary beating, and an accumulation of mucus and cell debris that triggers coughing (Ahuja et al., 2004). Pertussis toxin is unique to the Bordetella pertussis species and is important in colonization, the disruption of host cell signaling pathways, and immune evasion (Mattoo et al., 2001). Adenylate cyclase toxin is an invasive toxin that is also important in the disruption of signal transduction pathways; in addition it also plays a role in the disruption of immune effector cells (Ahuja et al., 2004). Tracheal cytotoxin (TCT) is a disaccharide tetrapeptide that is derived from the cell wall (Coote, 2001). This toxin has been observed to cause paralysis of the cilia and extrusion of ciliated cells in hamster tracheal organ cultures and has also been shown to inhibit DNA synthesis in hamster tracheal epithelial cell cultures, all of which could lead to mucus accumulation and coughing. The destruction of the cilated epithelial cells in a B. pertussis infection is thought to be due to the production of nitric oxide by non-ciliated, mucus secreting epithelial cells in response to the combination of TCT and lipopolysaccharide (LPS) (Coote, 2001). TCT is also associated with the characteristic whooping cough of B. pertussis infection and an increase in body temperature through the simulation of interlukin-1 (Babu et al., 2001). Dermonectoric toxin is a heat stable toxin that induces inflammation, vasoconstriction, and dermonecrotic lesions around colonies of B. pertussis in the respiratory tract (Babu et al., 2001). This toxin also affects the regulation of cell growth and division systems (Babu et al., 2001). Heat-labile toxin may also be involved in tissue damage during infection (Steele, 2004). www.ibl.fr/u447/u447.htm

Pertactin Outer membrane protein antigen present in all virulent strains Included in acellular pertussis vaccine

Bordetella parapertussis Infrequent, cause of whooping cough Disease is mild Pertussis vaccine do not give protection

Bordetella bronchiseptica Peritrichate flagella Antigenetically related to pertussis and abortus Occurs naturally in the respiratory tract of several sps of animals

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