pertussis
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Pertussis toxinClassification : Domain: Prokaryotes
Kingdom:BacteriaClass:BetaproteobacteriaOrder:BurkholderiaceaeGenus: BordetellaSpecies: B. pertussis
Nomenclature: Bordetella pertussis (B. Pertussis) is a small, coccobacillus. Coccobacillus are rod-shaped bacteria. Cocco comes from "cocci" meaning spherical shaped and bacillus comes from "bacilli" meaning elongated. B. pertussis, like most pathogenic bacteria, is Gram-negative.It is an encapsulated immotile aerobe that does not make spores.Protein exotoxin forming bacteria
Types :Eight species in the Bordetella genus:Three species in this genus are known to be pathogenic to humans. B. pertussis and B. parapertussis are very similar species.
B. bronchiseptica causes respiratory disease in various mammals and occasionally in humans .
The human pathology of the remaining five species is relatively unknown. B. avium and B. hinzii, are known to cause respiratory disease.
Areas of infection : - Mouth
- Nose - Throat.Risk groups:
-Unvaccinated children (especially infants)- Adolescents whose immunity has waned.- Adults whose immunity has waned.
Transmission; -Direct contact with droplets from coughing or
sneezing by an infected person- Can continue to transmit the bacteria three weeks after coughing spells have stopped- Can be carried by individuals who are immune and transmitted to those who are not.NOTE: It cannot survive in the environment; it must reside in a host either in small groups or singly.
It grows at an optimal temperature of 35-37ºC.
Cell and toxin Structure:Its cell structure : consists of an outer membrane, an inner membrane and a periplasmic space with a thin peptidoglycan layer in between. On its outer membrane, Bordetella pertussis has unusual lipoopolysaccharides (LPS), endotoxins.Toxin structure:
Pertussis toxin is a 105 kDa protein composed of six subunits: S1, S2, S3, (2)S4, and S5.And adenylate cyclase toxin, filamentous hemagglutinin ,
Pathology: Humans are its only host. Pertussis is a severe, highly contagious respiratory disease characterized by outbursts of coughing followed by “whooping” sound during breathing in. Often vomiting takes place with discharge of sticky mucus. Symptoms :
The symptoms of pertussis are similar to a common cold: runny nose, sneezing, mild cough, and low-grade fever.
Mechanism of pathogenesis:The disease pertussis has two stages:
1.Colonization(the attachment to and growth on ciliated cells)
2.Toxemic (organism produces a number of exotoxins which contribute to these symptoms.)
1.The two most important colonization factors are the filamentous hemagglutinin (FHA) and the pertussis toxin (PTx).
Filamentous hemagglutinin is a large (220 kDa) protein that forms filamentous structures on the cell surface. FHA binds to galactose residues on a sulfated glycolipid.
the pertussis toxin (PTx), is also involved in adherence to the tracheal epithelium. Pertussis toxin is a 105 kDa protein composed of six subunits: S1, S2, S3, (2)S4, and S5.. Some components of the cell-bound toxin (S2 and S3) function as adhesins, and appear to bind the bacteria to host cells.S2 binds specifically to a glycolipid called lactosylceramide, which is found primarily on the ciliated epithelial cells. S3 binds to a glycoprotein found mainly on phagocytic cells.
Toxicity: Mainly through elevating the cAMP level , result in disrupting cell function.Pertussis toxin:
The A subunit gains enzymatic activity and transfers the ADP ribosyl moiety of NAD to the membrane-bound regulatory protein Gi that normally inhibits the eukaryotic adenylate cyclase. The Gi protein is inactivated and cannot perform its normal function to inhibit adenylate cyclase .
The intracellular levels of cAMP increase .
Increased intracellular cAMP affects normal biological signaling. The toxin causes several systemic effects, among which is an increased release of insulin,
causing hypoglycemia .The role of the toxin in whooping cough is not known.It inhibits the early recruitment of neutrophils and macrophages, and interferes with the early chemokine production and the inhibition of the
neutrophil chemotaxis.
Adenylate cyclase toxin:This exotoxin penetrates the host cells, is activated by calmodulin and catalyzes the conversion of ATP to cAMP. Like pertussigen, it also inhibits phagocyte and NK cell functions.
the cAMP increase caused by this toxin is short-lived.
Tracheal cytotoxin:
This is a peptidoglycan-like molecule (monomer) which binds to ciliated epithelial cells, thus interfering with ciliary movement. In higher concentrations, it causes ciliated epithelial cell extrusion and destruction. The destruction of these cells contributes to pertussis.
Dermonecrotic (heat-labile) toxinDermonecrotic toxin is a very strong vaso-constrictor and causes ischemia and extravasation of leukocytes and, in association with tracheal cytotoxin, causes necrosis of the tracheal tissue
Diagnosis:Symptoms are characteristic. Laboratory diagnosis is made by obtaining a nasopharyngeal aspirate and primary culture on Bordet-Gengou medium (potato-glycerol-blood agar).
Prevention and treatment:
A killed whole bacterial vaccine is normally administered as DPT combination .
Erythromycin is the current drug of choice.