Any medical concept and for that matter any item to be memorized has following needs, acquire the concept, commit it to short and then long term memory, attach a handle to it for later recall, and rapid recall.
While flying for AANP conference I sat back in my seat and thought about how to present this pathogen in a way that it becomes sticky in student’s mind. It might be interesting for some of you to see how the lecture and images evolved as I strived to accomplish other goals. This pathogen is still in progress though!
Corynebacterium Properties
Gram +ive, non spore forming rods. Usually arranged in V or L shaped. These rods are club shaped with beady appearance. Beads are filled with highly polymerized polyphosphate. This is how high energy phosphate bonds are stored. These beads appear metachromatic. Metachromatic means that these beads appear red when stained with a dye that stains the rest of the cell blue. See the images below where I try to capture these ideas.
Figure 1.1: Gram +ive (purple color). Club shaped rods. Polychromatic beads with high energy phosphate bonds (reddish). Arranged in V or L.
Target Population
Corynebacterium primarily targets children.
Figure 1.2: Corynebacterium Diphtheria standing amongst children ready to infect them.
Mode of Transmission
Both the toxic and non-toxic species of Corynebacterium reside in the upper respiratory tract. Humans are the only reservoir for this pathogen. Transmission occurs via air-borne droplets. It can also infect an existing skin wound in people with poor skin hygiene.
Figure 1.3: Corynebacterium flying on a droplet from one person to another person.
Pathogenesis
Corynebacterium Diphtheria causes nervous and cardiac tissue damage by releasing an exotoxin in the blood. This is why the gray membrane in child’s throat should not be scrapped as it will cause bleeding and send a pile of exotoxin in the blood.
Corynebacterium needs a temperate lysogenic bacteriophage to be able to cause pathology.
Figure 1.4: a bacteriophage must become part of the Corynebacterium Diphtheria to enable it to make diphtheria exotoxin. Notice the spider like bacteriophage with models to make exotoxin unit B (hand) and the unit A (action guy).
Diphtheria Exotoxin and its Mechanism of Action
Exotoxin has two subunits:
- Subunit A for action.
- Subunit B for binding.
Figure 1.5: Club shaped beady rod with an exotoxin hanging from it, ready to go to work. The B subunit is the hand that will grab a receptor on the cell, and the A subunit is the action guy who will disable elongation factor 2 (EF2) leading to halting of the protein synthesis. Causing cell to die. (Note ideally there should be a bacteriophage sitting in this CD cell.)
Mechanism of Pathogenies
- Subunit B that helps bind with the receptor on a cell. Binding in turn leads to internalization of both the subunits as a vesicle. In our diagrams I made this subunit as a hand to grab the cell.
- Subunit A helps with action. This subunit is cleaved in the vesicle and then released in the cytoplasm. There it causes ADP-ribosylation of the elongation factor 2. Elongation factor 2 is responsible to grab transfer RNAs with amino-acids and bring them to ribosome where proteins are manufactured. The amino-acid attached to the tRNA is used to elongate the protein chain. Elongation factor 2 when ADP-ribosylated fails to bind with the tRNA. Result is halting of the protein synthesis which leads to the cell death.
Figure 1.6: A rough sketch showing diphtheria exotoxin subunit B binding to the cell receptor (hand grabbing the cell receptor). Note the subunit A sitting ready to go in and stop the EF2 (lower right.) Middle right shows that the EF2 (fish) is bringing a tRNA to a ribosome to help elongate the protein being synthesized in the ribosome.
Clinical Findings
- Rare in the US.
- Thick gray sticky pseudomembrane composed of necrotic epithelial cells, inflammatory cells, dead bacteria, exotoxin, etc. This membrane is observed over the tonsil and throat. It is usually darker, thicker, and larger in quantity than strep throat.
- Fever
- Sore throat
- Cervical adenopathy
Complication
- Airway obstruction due to the membrane extending into the larynx and trachea.
- Myocarditis with arrhythmia and circulatory collapse.
- Weakness or paralysis due to damage to the nerves. Cranial nerves are more frequently involved. Regurge of fluids through nose due to weakness or paralysis of the soft palate and pharynx.
Cutaneous Diphtheria
- Gray membrane on ulcerated skin.
- Indolent and noninvasive to the surrounding tissue.
Treatment
As soon as you suspect that the patient has diphtheria you should immediately start them on the diphtheria antitoxin. This antiserum is made in horse so hypersensitivity must be checked. The antitoxin will bind the free exotoxin and neutralize it. This is the treatment of choice.
Penicillin G or Erythromycin will then kill the pathogen reducing the exotoxin production.
Culture
Corynebacterium Diphtheriae grows on potassium tellurite and loffler’s medium.
Figure 1.7: two loafs of bread (loaffler’s) had a bet that the pathogen is corynebacterium or not. One of them was correct. So the other one is saying that I TELL you U were RITE (K+ Tellurite).
Note
Hope you enjoyed studying with such sketches. Feedback is appreciated. And, if you can contribute even better art then we all will be grateful to you.
Mobeen Syed