Corynebacterium diphtheriae

C.dip

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General features of Corynebacterium
Gram positive rodaerobicrelatively lengthy generation time
Reservoir
Humans
Transmissioin is via:
Respiratory dropletsdirect contact with the skin
Pathogenesis
-virulence is due to production of the diptheria exotoxin which causes damage-the toxin is immunogenic which stimulates production of antitoxin antibodies within hours-rare in US due to vaccination-organism can asymptomtically colonize the skin and oropharynx
Virulence Factors
1. diphtheria exotoin
Diphtheria exotoxin
-protein with potent cytotoxin features-Tox gene is encoded by a bacteriophage but the regulatory element is on the chromosome-iron serves as a co repressor (when iron high, toxin expression low)-as organism multiplies, it depletes iron which leads to increased expression of toxin-inhibits protein synthesis leading to cell death-has A-B subunit structure
Describe A B structure of the diphtheria exotoxin
-Contains an active A subunit that catalyzes toxin activity and a binding B subunit that mediates receptor binding and membrane insertion-the receptor for the B subunit is heparin binding epidermal growth factor that is found on tissues of heart, muscles, respiratory tract-after receptor binding, the toxin is engulfed by the cell-once inside the cell, the A and B subunit separate and the A subunit is released into the cytoplasm -A and B separate-A blocks elongation factor 2 (EF2)therefore protein synthesis halted
Clinical Presentations
1. respiratory infections2. skin infections
1. Respiratory infections
-incubation period is 2-4 days -starts out as a sore throat-a patch of pseudomembrane develops on either side of the tonsils, uvula, soft palate, or pharyngeal wall-major swelling of the lymph nodes in neck = bullneck-complications include --obstruction of airway--systemic effects of toxin due to absorption into blood--can lead to organ damage and myocarditis
Describe the pseudomembrane
-membrane caused by the action of the diphtheria exotoxin on the epithelium at the site of the infections-can move up towards nasopharynx or down towards trachae-very well adhered- bleeding and additional tissue damage if there is an attempt to remove
2. Skin infection
-leads to lesions ranging from a simple pustule to a chronic, non-healing ulcer-can see a coinfection with S.aureus or S.pyogenes-complications are infrequent-not a reportable disease so case numbers are unknown
Treatment
-neutralization of toxin by administering diphtheria antitoxin-administration of toxoid vaccine-use penicillin or erythromycin to eliminate organisms
Prevention
-vaccine uses the toxoid (inactivated toxin)-this stimulates immunity to the toxoid- not the organism-for children, either DTaP, DT-both require 5 doses as 2,4,5,15-18 months, 4-6years-adults get either Tdap or Td -boosters needed every 10 years