This gives an understanding of Corynebacterium diphtheriae , the disease it causes, epidemiology, pathogenesis and diagnosis.

1. Corynebacterium diphtheriae
Clinical Microbiology
Rishabh Parashar (A0999319008)

2. Introduction
Corynebacterium diphtheriae
• Responsible for causing Diphtheria.
• Also known as Klebs-Loffler bacillus.
• Infection occurs majorly in the upper respiratory tract
• Might cause Fever, sore throat and malaise.
• Thick green layer is observed on the site of infection.
• Transmission happens with the help of droplets,
secretions or direct contact.
• Proper vaccination around the world has made it a
rather rare disease, especially in developed countries.

3. Corynebacterium diphtheriae
Morphology and classification
Corynebacterium diphtheriae
• Gram-positive rods.
• Pleomorphic in nature.
• Club shaped ( swelling is observed on either or both ends)
• Non-capsulate, non-spore forming and non-motile.
• High GC content
• Four subspecies: C.d. gravis, C.d. mitis, C.d. intermidius, C.d.
belfanti. Gram stain

4. Corynebacterium diphtheriae
Media for Cultivation
• Blood agar
• Loeffler’s serum slope
• Tellurite blood agar
• Tinsdale’s medium
• Hoyle’s tellurite lysed-blood agar
Blood agar Tinsdale’s medium

5. Epidemiology
Corynebacterium diphtheriae
• Occurrence is rare in developed countries because of proper mass immunization.
• Diphtheria is still considered as an endemic in some developing and under-developed
counties of South America, Southeast Asia and Africa (Poor health infrastructure).
• Out of the 4,680 cases in 2013, 80% were from India and Indonesia alone.
• C. ulcerans is still very common in industrialized countries.
• ( the level of health infrastructure can be understood by paying attention of the
figure)Only 30% of the countries reached the target of 80% DPT3 coverage.
• Schick test played vital role in assessing immunity to diphtheria toxin.

6. Epidemiology
Corynebacterium diphtheriae

7. Pathogenesis
Corynebacterium diphtheriae
• Diphtheria toxin is responsible for causing the disease.
• Lesions formed are usually surrounded by a pseudo-membrane.
• Pathogenesis of Diphtheria can be determined on the basis of two
factors:
1. Ability of the strain to colonize nasopharyngeal cavity or skin.
2. Ability of the strain to produce toxin.

8. Toxin Production
Pathogenesis
Corynebacterium diphtheriae
• Tox gene is responsible for production of Diphtheria toxin.
• An iron-activated repressor – DtxR regulates tox gene.
• When iron becomes growth rate limiting substrate, iron dissociates from
DtxR, tox gene is depressed which results in the formation of diphtheria
toxin.
• The toxin is composed of three structural domains:
Receptor
Catalytic
activity
Transmembrane
delivery

9. Toxin Production
Pathogenesis
Corynebacterium diphtheriae
Steps involved in intoxicating a cell:
• Binding of toxin to its cell surface receptor.
• Internalization of the toxin by receptor-mediated
endocytosis.
• Insertion of the transmembrane domain into the
membrane and the facilitated delivery of the
catalytic domain to the cytosol.
• ADP-ribosylation of EF-2, which results in the
irreversible inhibition of protein synthesis.

10. Diagnosis and Control
Corynebacterium diphtheriae
Diagnosis:
• Cotton tips are used to swab tonsils or calcium alginate swabs may be used to collect nasal swabs.
• After isolation, the C. diphtheria is identified as mitis, intermedius or gravis.
• Toxicity of strain is determined by Elek immunodiffusion test which is based on formation of toxin-
antitoxin band.
Control:
• Majorly dependent on immunization with diphtheria toxoid (formaldehyde-inactivated diphtheria toxin)
• For antibiotic treatment, macrolides and benzylpenicillin are usually prefered.