Structure and Morphology of Bordetella pertussis and Corynebacterium diphtheriae
1. Bordetella pertussis
Bordetella pertussis is a small, aerobic, Gram-negative coccobacillus. It is non-motile and requires enriched media for growth due to its fastidious nature. The bacterium produces several antigenic and biologically active components, including pertussis toxin (PT), filamentous hemagglutinin (FHA), agglutinogens, adenylate cyclase toxin, pertactin, and tracheal cytotoxin. These components are critical virulence factors that allow the organism to adhere to respiratory epithelial cells, evade host immune defenses, and cause disease.
2. Corynebacterium diphtheriae
Corynebacterium diphtheriae is a Gram-positive, non-spore-forming rod with a characteristic club-shaped morphology. It is non-motile and facultatively anaerobic. The bacterium often appears in palisades or “Chinese letter” arrangements under the microscope due to its snapping division. Its virulence depends on the production of diphtheria toxin (DT), which is encoded by a tox gene introduced via lysogenic conversion by a β-phage.
Significance of Virulence Factors
1. Bordetella pertussis
The virulence factors of B. pertussis include:
- Pertussis Toxin (PT): A major exotoxin that disrupts cellular signaling by ADP-ribosylating G proteins, leading to increased cyclic AMP levels in host cells.
- Filamentous Hemagglutinin (FHA): Facilitates adherence to ciliated epithelial cells.
- Adenylate Cyclase Toxin: Inhibits phagocytosis by increasing intracellular cAMP in immune cells.
- Tracheal Cytotoxin: Damages ciliated epithelial cells, impairing mucociliary clearance.
These factors collectively paralyze the respiratory epithelium and evade immune responses.
2. Corynebacterium diphtheriae
The primary virulence factor of C. diphtheriae is:
- Diphtheria Toxin (DT): An AB exotoxin that inhibits protein synthesis by ADP-ribosylating elongation factor 2 (EF-2). This leads to cell death and tissue necrosis.
- Lysogenic conversion by a β-phage carrying the tox gene is essential for toxin production.
Epidemiology
1. Bordetella pertussis
Pertussis remains a global health concern despite widespread vaccination. It primarily affects infants under six months who are not fully vaccinated but can also infect adolescents and adults with waning immunity. Pertussis outbreaks have been linked to the transition from whole-cell vaccines to acellular vaccines due to reduced long-term immunity.
2. Corynebacterium diphtheriae
Diphtheria occurs worldwide but is more common in areas with low vaccination coverage. Outbreaks are often associated with poor sanitation or disruptions in healthcare systems. Transmission occurs via respiratory droplets or contact with infected lesions.
Pathogenesis
1. Bordetella pertussis
B. pertussis attaches to ciliated epithelial cells using FHA and other adhesins. The toxins produced paralyze the cilia, induce inflammation, and interfere with pulmonary secretion clearance. Pertussis toxin suppresses immune responses by inhibiting chemotaxis of neutrophils while promoting lymphocytosis.
2. Corynebacterium diphtheriae
C. diphtheriae colonizes the upper respiratory tract where it releases diphtheria toxin locally at infection sites. The toxin causes pseudomembrane formation in the throat due to necrosis of epithelial cells and inflammatory exudate accumulation. Systemic absorption of DT can lead to myocarditis or neuropathy.
Mechanism of Action of Toxins
- Pertussis Toxin: ADP-ribosylates G proteins involved in signal transduction pathways, leading to dysregulated cellular functions such as impaired phagocytosis.
- Diphtheria Toxin: Inhibits protein synthesis by targeting EF-2 through ADP-ribosylation, resulting in cell death.
Role of Lysogenic Conversion
Lysogenic conversion plays a critical role in C. diphtheriae’s pathogenicity as it enables the bacterium to produce diphtheria toxin through integration of the tox gene carried by a β-phage into its genome. Without this conversion, C. diphtheriae would lack its primary virulence factor.
Laboratory Diagnosis
(a) Bordetella pertussis
Diagnosis involves:
- Culture: Gold standard but requires specialized media like Regan-Lowe agar.
- PCR: Highly sensitive for detecting bacterial DNA during early stages.
- Serology: Useful for later stages when culture/PCR sensitivity decreases.
(b) Corynebacterium diphtheriae
Diagnosis includes:
- Culture: Growth on selective media like tellurite agar.
- Toxigenicity Testing: Elek test confirms toxin production.
- PCR: Detects tox gene presence.
The identification of toxins rather than just organisms is crucial because non-toxigenic strains do not cause severe disease.
Treatment
(a) Bordetella pertussis
Antibiotics such as macrolides (e.g., azithromycin) are used primarily during early stages to reduce transmission rather than alter disease course significantly once symptoms appear.
(b) Corynebacterium diphtheriae
Treatment includes:
- Administration of antitoxin for neutralizing circulating DT.
- Antibiotics like penicillin or erythromycin eliminate bacterial carriage.
Prevention and Vaccination
Vaccines
1. Bordetella pertussis
The acellular pertussis vaccine (aP) contains purified antigens such as PT, FHA, and pertactin instead of whole-cell components:
- Administered as part of DTaP vaccine series at 2, 4, 6 months; booster doses at 15–18 months and 4–6 years.
- Adolescents/adults receive Tdap booster every 10 years.
Side effects include mild fever or injection site reactions but rarely severe allergic responses.
2. Corynebacterium diphtheriae
The DTaP vaccine also protects against diphtheria using an inactivated form of DT:
- Same schedule as above for children; boosters recommended every 10 years.
Adverse effects are similar: mild local reactions or fever.
Significance
Identifying toxins rather than organisms ensures accurate diagnosis since only toxigenic strains cause severe disease manifestations like systemic complications.
