bordetella pertusis

1. Bordetella pertussis
Presented by: Hina Amir
TOPIC

2.  Introduction
 Effect on human
 Factors
Transmission
Binding
Invasion
Tissue damage
 Vaccination
 Today's perspective
CONTENTS

3. • (Hoppe 1999) , Todar 2004)
 Gram-negative
 Aerobic
 Nonmotile
 Coccobacillus
 Size: 0.8-0.4 um
 Human Pathogen
 Isolated in 1906
by Bordet and
Gengou.
 Habitat: mammalian
respiratory epithelium
WHOOPING COUGH
Bordetella pertussis

5. (Todar 2004). (Todar 2004, Wood and Friedman 1998).
 STAGE 1:
Catarrhal or colonization phase.
1-2 Weeks. symptoms resemble a cold or an
upper respiratory infection. coughing, fever.
Coryza  STAGE 2:
The toxemic, or paroxysmal.
• 1-6 weeks, but may persist for up to 10 weeks
characterized by severe, prolonged coughing.
Cyanosis, Vomiting. This coughing is accompanied
by the inspiratory “whoop” at this stage
 STAGE 3:
Convalescent phase.
Usually 7-10 days; range of 4-21 . marked by
reduction in attacks of severe coughing over
three to four weeks
 Complications - vomiting, pneumonia. Fits/ Low
Glu/Hyperinsulinaemia.
 Classically referred to as the "100 day" cough.

7. Transmittion
• Parton, R.(1999)
 Person to person via
•Aerosolized droplets from cough or sneeze
•Direct contact with secretions from respiratory tract of
infectious person
Older children and adults are important sources of disease for
infants and young children. Infants <12 months have greatest
risk for complications and death
 Pertussis, or whooping cough, is a highly contagious
respiratory tract infection. It affects an estimated 39 million
people each year, and kills 297,000 people worldwide.

8. • Parton, R.(1999)

9.  Bvg locus encodes proteins that transmit extracellular signals to
the cellular transcription machinery, causing changes in gene
expression.
 With the exception of tracheal cytotoxin, expression of virulence
factors is coordinately regulated by the products of the bvg locus
codes for BvgA, BvgS, BvgR.
 BvgA is activated by phosphorylation, following which it activates
the promoters P1, P2, P3, P4, PFHA, and other promoters of the
Virulence Activated Genes (vag), a class of loci including genes
encoding the adhesins and toxins.

11. • http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit2/bacpath/u1fig26a.html
ADHESINS:
Filamentous
hemagglutinin
adhere to galactose
residues of the
glycolipids-----Epithelial
cells.
Pertussis toxin
1 subunit---bacterial
cell wall
2 subunit----glycolipids
on membrane
Pertactin
further enables the
bacteria to adhere
to cells.

12. Pertussis toxin (PT)
 5 subunits (S1 to S5), in which the S1 subunit is the active portion and
S2-S5 subunits are responsible to bind with receptors on target cells.
(PT) binds to the membrane, the toxic subunit (S1) is inserted and
5'ADP ribosylation catalyzes a membrane protein, GI and is related to
the control of the intracellular adenylate cyclase.
This increases intracellular levels of cAMP leading to disruption of
cellular functions, decrease in phagocytic function of phagocytes such as
chemotaxis, engulfment, oxidative burst and bactericidal killing.
lymphocytosis and alteration of hormonal activities that are regulated
by cAMP, such as increased insulin and histamine production

13. Filamentous hemagglutinin . (FHA)
Protein, participate in the interaction of B. pertussis with host cells,
classified as an adhesion,
filamentous structure about 2nm wide and 50nm long, folded into
a monomeric rigid.
Mature FHA recognize receptors:
(1) the first, for binding to sulphated sugars on mucus secreting
epithelial cells,
(2) A region comprising CR3 integrins on macrophages and ciliary
cells
(3) the carbohydrate recognition domain (CRD on macrophages
and ciliated cells25

15. Pertactin (PRN)
PRN can contribute to bacterium-host cell interaction as an
adhesin PRN was found to have a role in defense against neutrophils
(PMN), suggesting immunomodulation with consequences similar to
those of adenylate cyclase toxin.
Arginine-Glycine-Aspartic acid mimic mammalian adhesion
proteins
Tracheal Cytotoxin (TCT)
This disaccharide-tetrapeptide, derived from peptidoglycan, kills
respiratory epithelial cell by a complex mechanism involving
intracellular interleukin 1 and nitric oxide
ciliostasis

16. • LPS
• 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.
Fimbriae (FIM)
These surface appendages, function as adhesins.
Binding of fimbriae to monocytes results in activation of CR3
(complement receptor type-3)31, the monocyte receptor of FHA.
Dermonecrotic toxin (DNT)
It is a heat-labile toxin and is considered contributes to
localized tissue destruction in human infections, although
further studies are needed to confirm its role in the
mechanism of pathogenicity of B. pertussis

17.  NO and the pro-inflammatory cytokines, IL-1and TNF-αinduced by bacterial toxins,
especially LPS, TCT and PT, as well as contributing to bacterial elimination, also
mediate local lung pathology and are responsible for many of the systemic and
neurological consequences of the infection. IFN-γsecreted early in infection by cells of
the innate immune system, and later in infection by Th1 cells, stimulates recruitment
and activation of macrophages and neutrophils and provides help for B cells to secrete
opsonizing . Opsonized or non-opsonized bacteria are taken up by neutrophils and
macrophages which are killed by NO or reactive oxygen intermediates.

18.  Antibodies :
neutralization of toxins
inhibition of binding by extracellular pertussis
facilitation of uptake by phagocytes.
 The bacterial protein BrkA, however, provides resistance to
killing. Opsonization may also facilitate uptake by
macrophages, within which bacteria can survive and evade
immune responses.
(Fernandez and Weiss , (Mills 2001). (Sumilla et al. 2004)

19. • The characteristics of this resurgence changed
dramatically in 2005.
• DTP (diphtheria, tetanus, pertussis)
• Possible Reasons
• 1) genetic changes in B. pertussis
• 2) a decrease in vaccine efficacy
• 3) a more rapid occurrence of waning immunity
• 4) increased recognition and reporting of pertussis
• 5) newer laboratory diagnostic tests.
Cherry JD, Olin P (1999), Higgs,R.2012

20.  Syncope (temporary loss of consciousness/faint)
 Sleep disturbance
 Incontinence
 Rib fractures
 Complications among infants
◦ Pneumonia (22%)
◦ Seizures (2%)
◦ Encephalopathy (<0.5%)
 Death
◦ Infants, particularly those who have not received a primary
vaccination series, are at risk for complications and mortality.
20

21.  Prevention - Immunization with pertussis vaccine
 Treatment.
 Antibiotic treatment, usually erythromycin
- Increased fluids
- Increased rest
Antibiotic treatment of choice remains erythromycin for 14 days,
although currently used schemes successfully shortened, seven days.
 Other effective antibiotics to kill the bacteria, such asclarithromycin
and azithromycin. In case of resistance or intolerance tomacrolides,
the most convenient choice istrimethoprim-sulfamethoxazole.

22.  Babu, M. M., J. Bhargavi, R. S. Saund, S. K. Singh, 2001. Virulence Factors of Bordetella
pertussis. Current Sciency 80: 1512-1522.
 Mouallem, M., Z. Farfel, E. Hanski, 1990. Bordetella pertussis Adenylate Cyclase Toxin:
Intoxication of Host Cells by Bacterial Invasion. Infection and Immunity 58: 3759-3764.
 Pittman M. The concept of pertussisas a toxin-mediated disease.Pediatr Infect Dis J. 1984;3:467.
 Cherry JD, Olin P (1999) The science and fiction of pertussis vaccines. Pediatrics 104: 1381–
1383. doi: 10.1542/peds.104.6.1381
 Hewlett et al. 2014. Pertussis Pathogenesis - What We Know and What We Don’t Know. J.
Infectious diseases.209.982-985
 Higgs, R. 2012. Immunity to the respiratory pathogen Bordetella pertussis

23. Atkinson W, Hamborsky J, McIntyre L,
Wolfe S, eds. (2007). Epidemiology and
prevention of vaccine preventable
disease. (10th Ed., pp. #81-100).
Atlanta, Georgia: Center for Disease