Gram-Positive Pathogens: High G+C Bacteria (Corynebacterium)

Gram-Positive Bacteria: High G+C Pathogens

Overview of High G+C Gram-Positive Bacteria

High G+C Gram-positive bacteria are a diverse group characterized by a high proportion of guanine and cytosine nucleotides in their DNA. This group includes several medically important genera, such as Corynebacterium, Mycobacterium, Propionibacterium, Nocardia, and Actinomyces. These bacteria can be classified based on their morphology into bacilli (rod-shaped) and filamentous forms.

• Bacilli: Corynebacterium, Mycobacterium, Propionibacterium

• Filamentous: Nocardia, Actinomyces

High G+C Bacilli: Corynebacterium

General Characteristics

Corynebacterium species are non-endospore forming, Gram-positive rods commonly found in plants and animals. They inhabit the skin and respiratory, intestinal, urinary, and genital tracts. These bacteria reproduce by binary fission (specifically, snapping division), which leads to characteristic V-shapes and palisade arrangements. A distinctive feature is the presence of metachromatic granules (polyphosphate inclusions).

• Non-endospore forming

• Snapping division produces V-shapes and palisades

• Metachromatic granules are diagnostic

• Commonly found on skin and mucosal surfaces

Pathogenic Species: Corynebacterium diphtheriae

Corynebacterium diphtheriae is the causative agent of diphtheria, a serious respiratory disease. Its pathogenicity is primarily due to the production of diphtheria toxin.

Virulence Factor: Diphtheria Toxin

The major virulence factor of C. diphtheriae is the diphtheria toxin, encoded by a lysogenic bacteriophage. The toxin is an A+B type exotoxin that inhibits protein synthesis in host cells.

• Lysogenic phage carries the gene for diphtheria toxin

• A+B subunit structure:

  • B subunit binds to host cell growth factor receptors, facilitating endocytosis

  • A subunit is released into the cytosol, where it enzymatically inactivates elongation factor 2 (EF2), halting protein synthesis

• Result: Cell death due to inhibition of protein synthesis

Equation:

$\text{Diphtheria Toxin (A subunit)} + \text{EF2} \rightarrow \text{Inactivated EF2} \rightarrow \text{Inhibition of protein synthesis}$

Pathogenesis and Disease: Diphtheria

Diphtheria is transmitted via respiratory droplets or direct contact. The disease severity depends on the immune status of the host.

• Transmission: Respiratory droplets, direct contact

• Symptoms: Fever, pharyngitis, and formation of a thick pseudomembrane in the throat

• Pseudomembrane: Composed of dead cells, leukocytes, bacteria, and fibrin; can obstruct airways and cause suffocation

• Complications: Toxin absorption into the bloodstream can lead to systemic effects and organ damage

Example: Severe diphtheria can cause airway obstruction and myocarditis due to systemic toxin effects.

Diagnosis, Treatment, and Prevention

Diagnosis of diphtheria is based on clinical presentation and laboratory tests. Key diagnostic features include the presence of a pseudomembrane and detection of toxin production.

• Pseudomembrane in the throat is a hallmark sign

• Elek test: Immunodiffusion assay to detect diphtheria toxin

• Loeffler’s medium: Used for culturing Corynebacterium species

• Treatment:

  • Antitoxin administration to neutralize circulating toxin

  • Antibiotics (e.g., erythromycin) to eliminate bacteria

• Prevention:

  • DTaP vaccine (Diphtheria, Tetanus, and Pertussis) given in childhood, with booster every 10 years

Example: The Elek test is used to confirm toxin production by C. diphtheriae isolates.

Summary Table: Key Features of Corynebacterium diphtheriae

Feature	Description
Cell Morphology	Gram-positive, non-endospore forming rods; palisade arrangement
Virulence Factor	Diphtheria toxin (A+B exotoxin)
Transmission	Respiratory droplets, direct contact
Clinical Disease	Diphtheria (fever, pharyngitis, pseudomembrane)
Diagnosis	Pseudomembrane, Elek test, culture on Loeffler’s medium
Treatment	Antitoxin, erythromycin
Prevention	DTaP vaccine

Additional info: The notes focus on Corynebacterium diphtheriae as a representative of High G+C Gram-positive bacilli. Other genera (e.g., Mycobacterium, Propionibacterium, Nocardia, Actinomyces) are mentioned in the overview but not detailed in these slides.