Bordetella pertusis
Transcript of Bordetella pertusis
Bordetella pertussis
Presented by: Hina Amir
TOPIC
Introduction
Effect on human
FactorsTransmission
Binding
Invasion
Tissue damage
Vaccination
Today's perspective
CONTENTS
• (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
(Todar 2004). (Todar 2004, Wood and Friedman 1998).
STAGE 1:
Catarrhal or colonization phase.
1-2 Weeks. symptoms resemble a cold or anupper respiratory infection. coughing, fever.Coryza
STAGE 2:
The toxemic, or paroxysmal.
• 1-6 weeks, but may persist for up to 10 weekscharacterized by severe, prolonged coughing.Cyanosis, Vomiting. This coughing is accompaniedby the inspiratory “whoop” at this stage
STAGE 3:
Convalescent phase.
Usually 7-10 days; range of 4-21 . marked byreduction in attacks of severe coughing overthree to four weeks
Complications - vomiting, pneumonia. Fits/ Low Glu/Hyperinsulinaemia.
Classically referred to as the "100 day" cough.
Transmittion
• Parton, R.(1999)
Person to person via•Aerosolized droplets from cough or sneeze•Direct contact with secretions from respiratory tract ofinfectious person
Older children and adults are important sources of disease forinfants and young children. Infants <12 months have greatestrisk for complications and death
Pertussis, or whooping cough, is a highly contagiousrespiratory tract infection. It affects an estimated 39 millionpeople each year, and kills 297,000 people worldwide.
• Parton, R.(1999)
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 locuscodes 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.
• http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit2/bacpath/u1fig26a.html
ADHESINS:
Filamentous hemagglutininadhere to galactoseresidues of the glycolipids-----Epithelial cells.
Pertussis toxin 1 subunit---bacterial cell wall 2 subunit----glycolipidson membrane
Pertactinfurther enables the bacteria to adhere to cells.
Pertussis toxin (PT) 5 subunits (S1 to S5), in which the S1 subunit is the active portion andS2-S5 subunits are responsible to bind with receptors on target cells.(PT) binds to the membrane, the toxic subunit (S1) is inserted and5'ADP ribosylation catalyzes a membrane protein, GI and is related tothe control of the intracellular adenylate cyclase.This increases intracellular levels of cAMP leading to disruption ofcellular functions, decrease in phagocytic function of phagocytes such aschemotaxis, engulfment, oxidative burst and bactericidal killing.lymphocytosis and alteration of hormonal activities that are regulatedby cAMP, such as increased insulin and histamine production
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 intoa monomeric rigid.Mature FHA recognize receptors:(1) the first, for binding to sulphated sugars on mucus secretingepithelial cells,(2) A region comprising CR3 integrins on macrophages and ciliarycells(3) the carbohydrate recognition domain (CRD on macrophagesand ciliated cells25
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, killsrespiratory epithelial cell by a complex mechanism involvingintracellular interleukin 1 and nitric oxideciliostasis
• LPS
• Like most Gram negative pathogens, B. pertussis alsocontains a Lipopolysaccharide coat that acts as anEndotoxin and can aid colonization by agglutinatinghuman 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, althoughfurther studies are needed to confirm its role in themechanism of pathogenicity of B. pertussis
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.
Antibodies :neutralization of toxinsinhibition of binding by extracellular pertussisfacilitation of uptake by phagocytes. The bacterial protein BrkA, however, provides resistance to
killing. Opsonization may also facilitate uptake bymacrophages, within which bacteria can survive and evadeimmune responses.
(Fernandez and Weiss , (Mills 2001). (Sumilla et al. 2004)
• The characteristics of this resurgence changeddramatically 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
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
Prevention - Immunization with pertussis vaccine Treatment. Antibiotic treatment, usually erythromycin
- Increased fluids- Increased restAntibiotic treatment of choice remains erythromycin for 14 days, although currently used schemes successfully shortened, seven days.
Other effective antibiotics to kill the bacteria, such as clarithromycinand azithromycin. In case of resistance or intolerance to macrolides, the most convenient choice is trimethoprim-sulfamethoxazole.
Babu, M. M., J. Bhargavi, R. S. Saund, S. K. Singh, 2001. Virulence Factors of Bordetellapertussis. 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 pertussis as 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
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