Classification
Gram-negative bacteria:
Most bacteria can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thin layer of peptidoglycan do not retain the crystal violet stain utilized in Gram staining. These bacteria do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative. These bacteria can be further classified according to morphology (diplococci, curved rods, bacilli, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteria can be more narrowly identified by growing them on specific media (triple sugar iron (TSI) agar) where their enzymes can be identified (urease, oxidase) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain
** Pleomorphic rod/coccobacillus
*** Require special transport media
General Characteristics
Basic features of Bordetella
- Gram-negative coccobacilli
- Encapsulated
- Non-motile
- Non-spore forming
- Obligate aerobes
Biochemistry and growth
- Very fastidious
- Do not ferment carbohydrates
- Inhibited by fatty acids (need media that absorb the fatty acids to grow)
- Difficult to culture; isolated on:
- Bordet-Gengou agar (blood, potato extract, and glycerol plus antibiotics and nicotinamide)
- Regan-Lowe medium (charcoal with defibrinated horse blood)
Pathogenic species
- B. pertussis (most important): causes pertussis (whooping cough)
- B. parapertussis: can also cause pertussis
- B. bronchiseptica: rare in humans, but can infect immunocompromised hosts
Gram stain of B. pertussis
Image: “Gram stain of Bordetella pertussis” by the CDC Public Health Image Library. License: Public domain.
Scanning electron micrograph of Bordetella bronchiseptica
Image: “File:Bordetella bronchiseptica” by the CDC/ Janice Carr. License: Public domain.
Bordetella Pertussis
Epidemiology
- Incidence worldwide: 24 million cases per year
- Deaths worldwide: approximately 161,000 per year
- Incidence in the United States: 15,000 cases in 2018
- Vaccination reduces the incidence significantly in young children, but does not confer lifelong immunity.
- Cyclical epidemics occur every 2–5 years.
- Disease is less severe in adolescents and adults than in young children.
Transmission
- No known environmental reservoirs
- Transmitted by respiratory droplets
- Many household contacts can have asymptomatic or very mild disease, frequently undiagnosed.
- Incubation period is 1 to 3 weeks (most commonly 7–10 days).
Pathophysiology
Pathogenesis:
- The 1st step is inhalation.
- Bacteria adhere to the ciliated epithelium of the nasopharynx and upper respiratory tract by various protein adhesins.
- Cause tissue damage and loss of protective epithelial cells by toxin production
- Results in microaspiration and cough
- Fatal cases are associated with:
- Necrotizing bronchiolitis
- Alveolar hemorrhage
- Fibrinous edema
- Intracellular bacteria in alveolar macrophages and ciliated epithelium (evade intracellular digestion)
Virulence factors:
- Filamentous hemagglutinin pili:
- Allow for attachment to ciliated, respiratory epithelium
- Pertussis toxin (A/B toxin):
- Ribosylates (inhibits) guanine nucleotide-binding protein (Gi)
- Increases cyclic adenosine monophosphate (cAMP)
- Impairs phagocytosis
- Causes lymphocytosis
- Adenylate cyclase toxin:
- Increases cAMP similar to the Bordetella anthracis EF-2 toxin
- Induces apoptosis of macrophages
- Tracheal toxin:
- Induces nitric oxide gas production
- Damages respiratory epithelium
Pathogenesis of Bordetella pertussis: Filamentous hemagglutinin binds to the ciliated epithelial cells, poisoning the cells, inhibiting the mucociliary elevation. Another mechanism is the prevention of intracellular digestion by phagocytosis, thereby evading the immune system.
Image by Lecturio.
Pathophysiologic mechanisms underlying the virulence and pathogenic factors
Image by Lecturio.
Clinical presentation
- Pertussis is a form of bronchitis.
- In children, classically has 3 stages:
- Catarrhal stage: congestion, coryza (runny nose), conjunctivitis, low-grade fevers (1–2 weeks)
- Paroxysmal stage (2–8 weeks):
- Severe coughing episodes on expiration
- “Whoops” on inspiration (whooping, paroxysmal cough)
- Post-tussive vomiting
- In infants, often presents with apnea instead of coughing paroxysms
- Convalescent stage: decreased frequency of coughing (4 weeks to months)
- In adults and adolescents:
- Often milder than in children
- Prolonged cough (> 2 weeks) is frequently the only symptom.
- Also known as the “100-day cough”
Chest radiograph of an 11-year-old patient with Bordetella pertussis infection Reinforcement of the perihilar bronchovascular reticulum and heterogeneous infiltrates on the inferior third of both lung fields.
Image: “Bordetella pertussis an agent not to forget: a case report.” by Melo N, Dias AC, Isidoro L, Duarte R. License: CC BY 2.0Identification
Specimen collection:
- Nasopharyngeal swab or aspiration
- Cotton-tipped swabs should not be used because they contain fatty acids toxic to B. pertussis.
- Polyester or calcium alginate swabs should be used instead.
- Specimen should be obtained from the posterior nasopharynx.
Tests:
- Culture (on special media)
- Polymerase chain reaction (PCR)
- Serology: primarily research applications
Prevention
- Acellular vaccine
- Component of the diphtheria, tetanus, and acellular pertussis (DTaP) combined vaccine
References
- Cornea P., & Lipsky B. (2020). Pertussis infection: Epidemiology, microbiology, and pathogenesis. UpToDate. Retrieved January 4, 2021, from https://www.uptodate.com/contents/pertussis-infection-epidemiology-microbiology-and-pathogenesis?search=bordetella&source=search_result&selectedTitle=4~41&usage_type=default&display_rank=4
- Cornea P., & Lipsky B. (2020). Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis. UpToDate. Retrieved January 4, 2021, from https://www.uptodate.com/contents/pertussis-infection-in-adolescents-and-adults-clinical-manifestations-and-diagnosis?search=bordetella&source=search_result&selectedTitle=1~41&usage_type=default&display_rank=1
- Guiso N. (2015). Bordetella pertussis. In Nicholson LK, & Janoff EN. (Eds.), Mucosal Immunology (4th ed.) https://www.sciencedirect.com/topics/medicine-and-dentistry/bordetella-pertussis
