Classification
Gram-positive bacteria:
Most bacteria can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thick layer of peptidoglycan retain the crystal violet stain utilized in Gram staining but are not affected by the safranin counterstain. These bacteria appear as purple-blue on the stain, making them gram positive. The bacteria can be further classified according to morphology (branching filaments, bacilli, and cocci in clusters or chains) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The cocci can also be further identified. Staphylococci can be narrowed down based on the presence of the enzyme coagulase and on their sensitivity to the antibiotic novobiocin. Streptococci are grown on blood agar and classified based on which form of hemolysis they employ (a, b, or g). Streptococci are further narrowed based on their response to the pyrrolidonyl-β-naphthylamide (PYR) test, their sensitivity to specific antimicrobials (optochin and bacitracin), and their ability to grow on sodium chloride (NaCl) media.
General Characteristics
Basic features
General characteristics of Corynebacterium species include:
- Gram-positive, club-shaped bacilli (coryne = club shaped)
- Non-motile
- Non-spore forming
- Non-encapsulated
- Aerobic or facultatively anaerobic
- Contain metachromatic (volutin) granules
Micrograph of Corynebacterium diphtheriae
Image: “12163” by the CDC/Graham Heid. License: Public domain.Growth and biochemical properties
- Catalase positive (split hydrogen peroxide into water and oxygen)
- Oxidase negative, indole negative
- Ferment glucose, starch, and glycogen
- Grow well at 37°C (98.6°F) on blood or serum-containing media:
- Hoyle’s/Tinsdale’s agar (tellurite medium; C. diphtheriae forms black colonies)
- Loeffler’s medium (enhances development of metachromatic granules)
Corynebacterium ulcerans colonies on a blood agar plate
Image: “Corynebacterium ulcerans 01” by the CDC/Dr. W.A. Clark. License: Public domain.
Corynebacterium diphtheriae on Tinsdale’s agar plate
Image: “16561” by the CDC. License: Public domain.
Clinically relevant species
- C. diphtheriae:
- Major pathogenic species
- Causes diphtheria (pharyngitis and cutaneous forms)
- Non-diphtherial Corynebacterium (diphtheroids):
- Mostly contaminants
- May be pathogenic, especially in immunocompromised hosts
- C. minutissimum:
- Normal skin inhabitant
- Can cause erythrasma: superficial infection of intertriginous areas
- Many species cause diseases in domestic animals.
Corynebacterium diphtheriae
Epidemiology
- In immunized individuals, the rate is low: < 5 per 100,000.
- Remains endemic in certain parts of the world (Brazil, Nigeria, India, certain parts of the former Soviet Union)
- No racial or sex predilection
- Can affect children and adults
Transmission
- Humans are the only known reservoir.
- Airborne droplets
- Direct contact with respiratory secretions
- Contact with skin lesions
- Can be transmitted by immunized and asymptomatic carriers
Virulence factors
- Not an invasive organism
- Pathogenicity is based on diphtheria toxin (exotoxin):
- Only produced if lysogenized by a β-bacteriophage
- Has 2 subunits:
- A—active
- B—binding
- B binds to the cell membrane and A enters the cell.
- Ribosylation of elongation factor (EF-2)
- Inhibits protein synthesis
- Causes cell death
Clinical presentation
Diphtheria (respiratory):
- Sore throat, malaise, cervical lymphadenopathy, low-grade fever
- Pharyngeal erythema with spots of white and gray exudate
- Can also have nasal, laryngeal, and tracheobronchial forms
- Pseudomembranes:
- Form in ⅓ of cases
- Composed of fibrin, necrotic debris, inflammatory cells, and organisms
- Tightly adherent to underlying tissue; bleeds with scraping
- Can spread to any portion of the respiratory tract
- “Malignant diphtheria”:
- Associated with extensive pseudomembranes (“pseudomembranous pharyngitis”)
- Severe “bull’s neck” lymphadenopathy
- Severe swelling of tonsils and uvula
- Can result in airway obstruction, respiratory stridor, and eventual death
- Exam tip: A common question stem may include an immigrant with a sore throat; physical exam reveals tonsils with grayish exudate.
Diphtheria: pediatric patient with diphtheria presenting with the characteristic grayish-white membrane covering the posterior pharyngeal wall
Image: “39015940254_849c8705a0_c” by Russell Watkins/Department for International Development. License: CC BY 2.0.
Patient infected by Corynebacterium: severe lymphadenopathy, known as “bull’s neck”
Image: “5325” by CDC. License: Public domain.
Complications/systemic toxemia:
- Cardiac:
- Myocarditis
- Arrhythmias
- Neurologic:
- Local neuropathies
- Cranial neuropathies
- Peripheral neuritis
- Renal: renal failure from hypertension or direct exotoxin effects
Cutaneous (wound) diphtheria:
- Initial papule that becomes a chronic, non-healing ulcer
- Ulcer is usually covered with a grey membrane.
- May be caused by toxin or non-toxin-producing strains
- In the United States, most common among alcoholic homeless men or drug users
Cutaneous diphtheria: chronic non-healing ulcer
Image: “1941” by the CDC. License: Public domain.
Identification
- Cultures:
- Should be obtained from throat or nose, including a portion of membrane
- Cultured on Loeffler’s or tellurite media
- Toxin detection:
- Elek’s test: isolates toxin-producing bacteria from the pseudomembrane
- Enzyme immunoassay (EIA)
Prevention
- Toxoid vaccine
- Infants are protected by maternal antibodies.
Management
- Passive immunization or anti-toxin: 1st line
- Antibiotics: Erythromycin or penicillin are the 1st choices for 14 days.
- Supportive management:
- Airway protection
- Bedrest
Mnemonic
“ABCDEFGs of Corynebacterium diphtheriae”:
- ADP-ribosylation
- β-bacteriophage
- Corynebacterium
- Diphtheriae
- Elongation Factor 2 (EF-2)
- Granules
References
- Barroso L.F., & Pegram P.S. (2020). Clinical manifestations, diagnosis, and treatment of diphtheria. UpToDate. Retrieved December 28, 2020, from https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-treatment-of-diphtheria?search=diphtheria&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H11
- Barroso L.F., & Pegram P.S. (2019). Epidemiology and pathophysiology of diphtheria. UpToDate. Retrieved December 28, 2020, from https://www.uptodate.com/contents/epidemiology-and-pathophysiology-of-diphtheria?search=diphtheria&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2
- Frassetto, L.A. (2019). Corynebacterium Infections Treatment & Management. https://emedicine.medscape.com/article/215100-treatment
- Nisha R. (2020). Corynebacterium diphtheriae: Properties, Pathogenesis, and Lab Diagnosis. https://microbeonline.com/corynebacterium-diphtheriae-properties-pathogenesis-diagnosis/
