Study Notes on Bordetella and Pertussis: Biology, Pathogenesis, and Control

The Bordetella Genus and Pertussis

Introduction

Bordetella is a genus of Gram-negative bacteria, with Bordetella pertussis as the causative agent of whooping cough (pertussis). Other species, such as B. parapertussis and B. holmesii, can cause pertussis-like illness but are not covered by current vaccines.

• Whooping cough is a highly contagious respiratory disease.

• Infants are at greatest risk of severe disease and death.

• Adults and adolescents often serve as reservoirs, transmitting the disease asymptomatically.

Learning Objectives

• Describe the biology, epidemiology, and clinical features of pertussis.

• Explain transmission, colonization, and host manipulation by B. pertussis.

• Identify key virulence factors (adhesins and toxins) and their roles.

• Discuss host immune responses and evasion strategies.

• Compare natural, whole-cell, and acellular vaccine responses.

• Discuss current challenges in pertussis control and future vaccine strategies.

Biology and Epidemiology of Pertussis

Brief History

• 1906: B. pertussis identified as the cause of whooping cough (Jules Bordet & Octave Gengou).

• 1920s: Heat-killed vaccine developed (Pearl Kendrick & Grace Eldering).

• Despite vaccination, pertussis remains endemic worldwide.

Recent Outbreaks

• 2024 England: 12,200 confirmed cases, 756 infants affected, 9 infant deaths.

• Maternal vaccination rates have declined, contributing to increased cases.

• Childhood vaccination schedule: 2, 4, 12 months, 3 and 5 years.

Vaccine Coverage and Challenges

• High case numbers persist even in countries with >90% vaccine coverage.

• Waning immunity after acellular vaccination leads to recurrent outbreaks.

• Surveillance underestimates true incidence; only ~5% of infections are reported.

• Pertussis remains a leading cause of death in young children globally.

Pathogenesis of Bordetella pertussis

Stages of Infection

1. Exposure: Transmission via water droplets; cannot survive outside host; adults act as reservoirs.

2. Adherence: Attachment to ciliated respiratory epithelium via multiple adhesins.

3. Invasion: Penetration through epithelium and evasion of host defenses.

4. Infection: Growth and production of virulence factors; manipulation of host immune response.

5. Toxicity: Toxin effects and tissue damage.

6. Tissue Damage/Disease: Persistent colonization and immune evasion.

Clinical Course

Stage	Length	Clinical Features
Catarrhal	7-10 days (range 4-21)	Coryza, mild cough, most infectious stage
Paroxysmal	1-6 weeks (up to 10)	Paroxysmal cough, inspiratory whoop, vomiting after cough, exhaustion
Convalescent	7-10 days (range 4-21)	Gradual recovery, persistent cough

Virulence Factors: Adhesins and Toxins

Key Adhesins of Bordetella pertussis

Adhesin	Function	Key Features	Role in Infection
FHA (Filamentous hemagglutinin)	Major surface adhesin	Binds carbohydrates on epithelial cells	Colonization, immune modulation
Fimbriae (Fim2/Fim3)	Hair-like appendages	Extend bacterial reach	Strengthen attachment, stabilize colonization
Pertactin (Prn)	Outer membrane autotransporter	Contributes to epithelial adhesion	Enhances binding, immune modulation
OtbAB (BP1251/1252)	Novel "orphan" B-subunit adhesins	Critical for initial adhesion	Potential vaccine target

BvgAS Regulatory System

• Controls expression of virulence genes in response to environmental signals.

• B. bronchiseptica switches between Bvg+ and Bvg- phases; B. pertussis is mostly locked in Bvg+ phase.

• Promoter architecture determines timing and level of gene expression.

FHA and Fimbriae

• FHA mediates attachment to ciliated epithelial cells and immune cells.

• Fimbriae assembled via chaperone-usher pathway; major subunits are Fim2 and Fim3.

• Variation in fimbrial subunit expression affects immune recognition and vaccine efficacy.

Pertactin (Prn)

• Contributes to stable adhesion and immune modulation.

• Prn-specific antibodies enhance phagocytosis; Prn-deficient strains evade antibody-mediated clearance.

• Vaccine-driven selection pressure has increased prevalence of Prn-deficient strains.

OtbAB (BP1251/1252)

• Novel adhesins critical for initial adhesion to respiratory tissue.

• Immunogenic and neutralized by antibodies.

Toxins and Host Manipulation

Pertussis Toxin (PT)

• Blocks chemokine signaling, preventing neutrophil and macrophage recruitment.

• Secreted via a Type IV secretion system.

Adenylate Cyclase Toxin (ACT)

• Enters phagocytes and raises cAMP, inhibiting phagocytosis and dampening inflammation.

Tracheal Cytotoxin (TCT)

• Peptidoglycan fragment released during cell wall remodeling.

• Damages ciliated epithelial cells, causing ciliary stasis and mucus accumulation.

• Stimulates IL-1 production, contributing to local inflammation.

Endotoxin (LPS)

• Lipid A structure differences between B. pertussis and B. bronchiseptica affect immune response.

• B. bronchiseptica LPS elicits strong TLR4 activation; B. pertussis LPS has reduced activation, aiding immune evasion.

Host Immune Response and Evasion

Immune Modulation

• FHA interacts with CR3 on macrophages, influencing uptake and cytokine responses.

• B. pertussis can suppress inflammation and delay clearance.

• Enhances immune cell recruitment, which can be exploited for transmission.

Immune Evasion

• Manipulation of immune pathways delays recruitment of neutrophils and macrophages.

• Combined effects of adhesins and toxins allow persistent colonization and transmission.

Diagnosis, Treatment, and Prevention

Diagnostic Methods

• Culture: Gold standard but low sensitivity after 2 weeks of symptoms.

• PCR (IS481): Most sensitive and rapid; useful within first 3 weeks of cough.

• Serology (anti-PT): Useful after 3 weeks when bacterial load is low.

Antibiotic Treatment

Drug	Dosage	Regimen	Side Effects	Contraindications
Erythromycin	Children: 40-50 mg/kg/day	4 divided doses for 14 days	GI disturbances	Allergy, liver disease
Azithromycin	10 mg/kg/day	Once daily for 5 days	GI upset	Allergy
Clarithromycin	15 mg/kg/day	2 divided doses for 7 days	GI upset	Allergy

Vaccination

• Whole-cell and acellular vaccines available.

• Routine vaccination recommended.

• Whole-cell vaccines confer better protection but have more side effects.

• Acellular vaccines have fewer side effects but waning immunity.

Current Challenges and Future Directions

• Resurgent outbreaks despite vaccination.

• Need for improved vaccines, surveillance, and continued research.

• Pathogen evolution and changing immune landscapes challenge control strategies.

Summary Table: Bordetella Virulence Factors

Factor	Type	Function
Pertussis Toxin	Toxin	Immune modulation
Fimbriae (Fim2, Fim3)	Adhesin	Attachment
Filamentous Hemagglutinin (FHA)	Adhesin	Attachment, immune modulation
Pertactin (Prn)	Adhesin	Stable adhesion, immune modulation
OtbAB (BP1251/1252)	Adhesin	Initial adhesion

References

• Northumbria University, AP0504 - 2024

• World Health Organization (WHO) data

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