Corynebacterium diphtheriae is a Gram-positive, club-shaped bacillus that is non-motile and non-capsulated, and it is the causative agent of diphtheria.
Diphtheria is a toxin-mediated disease, meaning that the clinical manifestations are primarily due to toxin production rather than bacterial invasion alone.
The severity of the disease can vary widely, ranging from mild, localized infections to severe systemic illness associated with high mortality.
A critical virulence factor of C. diphtheriae is its ability to produce diphtheria toxin, which determines its pathogenic potential.
Only toxigenic strains of C. diphtheriae are capable of causing classical diphtheria.
These toxigenic strains are lysogenic, indicating that they are infected with a specific corynebacteriophage.
The bacteriophage carries the tox gene, which encodes the diphtheria toxin and is essential for toxin synthesis and disease causation.
Diphtheria Toxin and Lysogeny
The diphtheria toxin is encoded by the tox gene, which is not a native part of all Corynebacterium diphtheriae strains.
This tox gene is carried by specific corynebacteriophages, highlighting the role of lysogeny in diphtheria pathogenicity.
Non-toxigenic strains of C. diphtheriae can become toxigenic if they are infected by a phage carrying the tox gene.
Once produced, the diphtheria toxin acts at the cellular level by inhibiting protein synthesis in host cells.
The toxin exerts its effect by inactivating elongation factor-2 (EF-2), a molecule essential for translation during protein synthesis.
Inactivation of EF-2 results in cessation of protein production, ultimately causing cell death.
This cellular damage leads to tissue necrosis, which is responsible for many of the local and systemic manifestations of diphtheria.
Classification of Corynebacterium diphtheriae
Corynebacterium diphtheriae is classified using two main systems that aid in its identification and epidemiological study.
One system is biotype classification, which is based on colony morphology, biochemical reactions, and the severity of disease produced by the organism.
The second system is lysotype classification, which depends on the organism’s sensitivity to different corynebacteriophages.
Among these systems, biotype classification holds major clinical and epidemiological importance, as it helps in understanding disease patterns, outbreak severity, and public health impact.
Biotypes of Corynebacterium diphtheriae
McLeod and Anderson classified Corynebacterium diphtheriae into three major biotypes to aid in laboratory identification and clinical correlation.
This classification is based on colony characteristics on tellurite blood agar, microscopic morphology, biochemical reactions, and the severity of disease associated with each type.
The three recognized biotypes of C. diphtheriae are Gravis, Intermedius, and Mitis.
Comparison of Biotypes of Corynebacterium diphtheriae
Gravis – “G = Grave & Great size”
Cells: Short rods, uniform staining, few or no granules
Biotyping of Corynebacterium diphtheriae plays an important role in epidemiological surveillance, as it helps track disease patterns and sources during outbreak investigations.
The gravis and intermedius biotypes are more frequently associated with severe outbreaks and higher disease severity, making their identification clinically significant.
Toxigenicity testing is essential for accurate diagnosis and management, using methods such as Elek’s test or PCR detection of the tox gene.
This testing is crucial because all biotypes of C. diphtheriae—gravis, intermedius, and mitis—can be either toxigenic or non-toxigenic, and disease severity depends on toxin production rather than biotype alone.
Conclusion
The biotypes of Corynebacterium diphtheriae, namely gravis, intermedius, and mitis, show clear differences in morphology, colony characteristics, biochemical behavior, and clinical severity.
Knowledge of these differences is essential for accurate laboratory diagnosis and correct interpretation of culture findings.
Understanding biotypes also aids in epidemiological studies, including tracking transmission patterns and identifying outbreaks.
This information is crucial for effective disease control and prevention strategies, particularly in regions where diphtheria continues to be endemic or epidemic.
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