Virulence factors of Bordetella pertussis

• Bordetella pertussis is a small non-motile, non-sporing ovoid.
• Gram negative cocco-bacillus.
• It measures about 1-1.5µm x 0.3µm and is haemolytic.
• Capsulated (fresh isolates from patients), strict aerobes and fastidious.
• On staining with toludine blue, metachromatic granules are seen.
• The genes coding for B. pertussis virulence factors are under the control of two sets of genes, which may act in tandem.
• The genes coding for adhesins and pertussis toxin are inactive at 25⁰C but active when the temperature is raised to 37⁰C.
• Changes in external environment may “turn off” the genes responsible for virulence to allow survival and dissemination by carriers infected with less virulent pertussis.
• The various virulence factors are as follows:

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a) Adhesins

• Adherence of B.pertussis to ciliated epithelial cells is essential for the pathogenesis of the organisms.
• This is mediated by capsular fimbriae or agglutinogens.
• The most important is filamentous haemagglutinin which also causes agglutination of red blood cells.

b) Toxins

• Toxins are of various types. They are:

i) Pertussis toxin(PT)

• It is a major virulent factor playing a central role in pathogenesis of whooping cough.
• It is produced only by B.  pertussis.
• PT is synonymous with the earlier terms such as, histamine sensitizing factor, islet cell activating factor.
• It has a molecular weight of 117,000 which are made up of two units, A and B.
• A unit is enzymatically active.
• The B-unit binds the toxin to the target cells and helps A-unit to cross the membrane.
• The toxin causes increased concentration of cAMP within the target cell.
• Production of PT is controlled by regulator PT gene.
• This toxin increases sensitivity to histamine and serotonin resulting in the increased susceptibility to anaphylaxis.
• It raises the level of insulin causing the reduction in blood sugar and inhibits epinephrine induced hyperglycaemia.
• It causes leukocytois by altering the migration pattern of lymphocytes.
• It is a potent T cell mitogen that causes accumulation of lymphocytes in the intravascular compartment.
• It increases binding to CR3 receptor of phagocytic cells and causes phagocytosis without the involvement of the superoxide burst.

ii) Adenylate cyclase-like toxin (ACT)

• It is produced by all Bordetellae except B. avium.
• ACT enters non-infected cells and causes intracellular increase in cAMP leading to intoxication of mammalian cells.
• It also inhibits chemotaxis and superoxide burst in polymorphonuclear leucocytes, which helps in intracellular survival of B. pertussis.

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iii) Tracheal cytotoxin(TCT)

• It is a Bordetella toxin derived from the peptidoglycan of cell wall and present in all species of Bordetellae.
• TCT induces ciliostasis in the epithelial cells, followed by extrusion of these cells from the epithelium of respiratory tract.
• This makes a person more prone to secondary infection.

iv) Endotoxin LPS

• It does not have any important role in pathogenesis but anti-LPS antibody aids in the immune clearance of Bordetellae.

References: 

i) https://www.nature.com/articles/nrmicro3235

ii) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC96429/

Virulence factors of Bordetella pertussis