Corynebacterium

Question 1

corynebacterium diphtheriae

Answer 1

all effects of the disease are due to an exotoxin

diphtheroids - other species are corynebacterium -> normal flora

Question 2

morphology and general characteristics

Answer 2

• aerobic, small , pleomorphic, non-spore forming GRAM POSITIVE RODS
• club-shaped rods from chinese letter or palisade arrangements
• may contain metachromatic granules that stain bluish-purple with methylene blue

Question 3

C.dip is grown on what medi

Answer 3

tinsdale agar that contains potassium tellurite which a.) inhibits the growth of normal flora and b.) reduced by C. diphtheriae to produce brown to black colonies

Question 4

Virulence factors - how does it work

Answer 4

1. Diphtheria toxin (DT) - the most important virulence factor of C. diphtheriae
   - acts to inhibit protein synthesis, exerting a cytotoxic effect.
   2 DT possess an A-B type structure characteristic of several exotoxins.
   a. The host cell receptor bound by the B subunit of DT is the heparin binding EGF-receptor.
   Following receptor mediated endocytosis, the B subunit facilitates the translocation of the A
   fragment from the phagosome to the cytosol.
   b. The target protein of the enzymatically active A subunit of DT is Elongation Factor - 2 (EF-2).
   During protein synthesis, EF-2 is required for translocation of polypeptidyl-tRNA from the acceptor
   to the donor site on the eukaryotic ribosome.
   DT catalyzes the transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD) to EF-2,
   resulting in the inhibition of protein synthesis and subsequent cell death.. ADP-Ribosylation is the
   mechanism of action for a number of exotoxins although the target protein may vary.

Question 5

control of diphtheria toxin production

Answer 5

a. The structural gene for DT (tox gene) is a component of a bacteriophage of C. diphtheriae calledbeta (β) phage. The β phage is a lysogenic or temperate phage. Only C. diphtheriae strains containing the β phage lysogen produce DT and cause diphtheria. Lysogenic conversion refers to the conversion of nontoxigenic diphtheria bacilli to toxigenic forms upon phage infection.

B. The tox gene of the β phage is regulated by a C. diphtheriae chromosomally encoded repressor,
DtxR, complexed with iron. Under low concentrations of iron, the tox gene would become de-repressed
causing an increase in toxin production. Thus iron plays a critical role in the expression of virulence.

Question 6

pathogenesis and clinical consideration

Answer 6

little invasive capacity-> will remain at intial site of infection in the pharynx

-Malaise, sore throat, and fever are present and a patch of exudate or membrane develops on the tonsils, uvula, soft palate, or pharyngeal wall.

This classic gray-white pseudomembrane is composed of bacteria, fibrin, dead epithelial cells, red cells and white cells which bleed when scraped. This pseudomembrane may obstruct breathing and detachment can lead to suffocation.

Cervical lymphadenitis and edema may
occur and produce a “bull-neck” appearance.

Toxin produced by C. diphtheriae in the pharynx can enter the circulation and disseminate leading to the
inhibition of protein synthesis in a variety of tissues.

Systemic complications may include peripheral
neuropathy, myocarditis and congestive heart failure.
Infection of the skin with C. diphtheriae may lead to cutaneous diphtheria - a chronic skin ulcer with a
dirty-gray membranous base.

Non-toxigenic strains of C. diphtheriae may produce a mild pharyngitis but NOT the typical toxic
manifestations of diphtheria

Question 7

lab diagnosis

Answer 7

isolation and identification of C. diphtheriae

• potassium tellurite/ tinsdale agar
• biochemical tests

Question 8

immunity

Answer 8

dependent on the presence of antibodies which neutralize DT

Question 9

treatment

Answer 9

Neutralization of toxin by passive administration of anti-toxin. The diphtheria antitoxin is prepared in
horses. The administration of heterologous antiserum could lead to serum sickness (type III
hypersensitivity). Complications may also include anaphylactic responses depending on the patient’s
history of previous heterologous passive immunizations.

Elimination of toxin producing bacteria by the administration of antimicrobial drugs, with erythromycin and penicillin being favored.

Question 10

epidemiology , prevention and control

Answer 10

-human is the only reservoir - acquired by contact of non-immune subjects with nasal carriers

active immunization with diphtheria toxoid prevents disease at ages 2,4,6 months and boosters at 15-18 months and one before school