Corynebacterium and Diphtheria Quiz

Non-Spore-Forming Gram-Positive Rods

• Corynebacterium diphtheriae is a non-spore-forming gram-positive rod.
• Other important pathogens in this group include Corynebacterium diphtheriae, Listeria monocytogenes, and Gardnerella vaginalis.

Corynebacterium diphtheriae

• Corynebacterium diphtheriae causes Diphtheria.
• Other Corynebacterium species (Diphtheroids) are implicated in opportunistic infections.

Genera and Species

• Various genera and species of Corynebacterium are listed, including toxigenic and nontoxigenic forms.

Disease

• Diphtheria is caused by C. diphtheriae.
• Diphtheroids are implicated in opportunistic infections.

Clinical Findings

• Respiratory diphtheria has an incubation period of 2-6 days.
• Inflammation begins in the respiratory tract, leading to sore throat, exudative pharyngitis, pseudomembrane formation, and low-grade fever.
• Prostration and dyspnea follow, potentially leading to suffocation if not treated promptly.
• Heart damage, visual disturbances, swallowing difficulties, and paralysis can occur but usually resolve.
• Death may result from asphyxia or heart failure.
• Cutaneous diphtheria results in ulcerating skin lesions covered by a gray membrane. The lesions are typically indolent and do not invade surrounding tissue.

Transmission

• Humans are the only natural host.
• Transmission occurs via airborne droplets.
• The organism can also infect the skin, especially in tropical regions or those with poor hygiene practices.

Pathogenesis

• Exotoxin production is essential for pathogenicity.
• Invasiveness is also needed for the organism to establish itself.
• Diphtheria toxin inhibits protein synthesis by ADP-ribosylation of elongation factor-2 (EF-2).
• The toxin affects all eukaryotic cells but has no effect on analogous factors in prokaryotic cells.

Diphtheria Exotoxin

• The exotoxin is a single polypeptide with two functional domains.
• The binding domain mediates toxin attachment to glycoprotein receptors on the cell membrane.
• The active domain has enzymatic activity to cleave nicotinamide adenine dinucleotide (NAD) and transfer the remaining ADP-ribose to EF-2, thus inactivating it.
• The DNA for the toxin is part of a temperate bacteriophage (beta phage) DNA that integrates into the bacterial chromosome during the lysogenic phase.
• C. diphtheriae cells not lysogenized by this phage do not produce exotoxin and are nonpathogenic.

Host Response

• A local inflammation in the throat, with a fibrinous exudate forming a gray pseudomembrane, is a common response.
• Antibodies neutralize exotoxin activity by blocking the binding domain from the receptors, preventing entry into the cell.

Immune Status

• Schick's test assesses immune status to diphtheria.
• An intradermal injection of diphtheria toxin is used.
• No inflammation indicates the presence of antitoxin and immunity.

Laboratory Diagnosis

• Diagnosis involves isolating the organism and demonstrating toxin production.
• Throat swabs are cultured on Loeffler's Serum Slope Agar, Tellurite Blood Agar, and Blood Agar plates.
• The presence of gray-black tellurium, reduced from a tellurium salt in the plate media, is a diagnostic indicator.
• Toxin production can be confirmed using animal inoculation, antibody-based gel diffusion precipitin tests, PCR assays, in vivo/in vitro toxigenicity tests, and Elek tests.

Treatment

• Antitoxin is the treatment of choice, given immediately due to the delay in laboratory confirmation.
• Antibiotics (penicillin G or erythromycin) are used along with antitoxin.
• Maintenance of an open airway is crucial.
• Treatment of bacteremia or endocarditis must be guided by antibiotic susceptibility tests.

Prevention

• Diphtheria is rare due to widespread childhood immunization.
• Immunization typically uses a combination of diphtheria toxoid, tetanus toxoid, and acellular pertussis vaccine (DTaP).
• Diphtheria toxoid is produced by treating the exotoxin with formaldehyde, inactivating its toxicity while preserving its antigenicity.
• Boosters are recommended periodically due to immunity waning.
• Prophylactic antibiotic treatment may be used for unimmunized contacts.

Other Corynebacterium species

• These organisms are often part of the normal human flora but can cause opportunistic infections in immunocompromised individuals.
• Examples include C. jeikeium, C. urealyticum, and C. ulcerans.