Corynebacterium diphtheriae is the pathogenic
bacterium that causes
diphtheria. It is also known as the
Klebs-Löffler bacillus, because it was discovered in 1884 by German
bacteriologists Edwin Klebs (1834 – 1912) and
Friedrich Löffler (1852 – 1915).
Classification
Four subspecies are recognized:
C. d. mitis,
C. d. intermedius,
C. d. gravis, and
C. d. belfanti.
The four subspecies differ slightly in their colonial morphology and
biochemical properties, such as the ability to metabolize certain
nutrients, but all may be toxigenic (and therefore cause diphtheria) or
not toxigenic.
C. diphtheriae produces diphtheria toxin which alters protein function in the host by inactivating the
elongation factor EF-2. This causes pharyngitis and 'pseudomembrane' in the throat. The
diphtheria toxin gene is encoded by a
bacteriophage found in toxigenic strains, integrated into the bacterial chromosome.
To accurately identify
C. diphtheriae, a
Gram stain is performed to show
Gram-positive, highly
pleomorphic organisms with no particular arrangement. Special stains like
Alberts's stain and
Ponder's stain are used to demonstrate the
metachromatic granules
formed in the polar regions. The granules are called as polar granules,
Babes Ernst granules, volutin, etc. An enrichment medium, such as
Löffler's medium, is used to preferentially grow
C. diphtheriae. After that, a differential plate known as
tellurite agar, allows all
Corynebacteria (including
C. diphtheriae) to reduce tellurite to metallic tellurium. The tellurite reduction is
colormetrically indicated by brown colonies for most
Cornyebacteria species or by a black halo around the
C. diphtheriae colonies.
A low concentration of iron is required in the medium for toxin
production. At high iron concentrations, iron molecules bind to an
aporepressor on the beta
bacteriophage, which carries the
Tox gene. When bound to iron, the apo
repressor shuts down toxin production.
[1] Elek's test for toxogenicity is used to determine whether the organism is able to produce the diphtheria toxin.
Pathogenesis
In areas where diphtheria is endemic,
C. diphtheriae in the
nasopharyngeal passageways is common. Toxigenic strains in susceptible
individuals can cause disease by multiplying and secreting diphtheria
toxin into either skin or nasopharyngeal lesions. The diphtheritic
lesion is often covered by a pseudomembrane composed of fibrin,
bacteria, and inflammatory cells. Diphtheria toxin can be
proteolytically cleaved into two fragments: an N-terminal fragment A
(catalytic domain), and fragment B (transmembrane and receptor binding
domain). Fragment A catalyzes the NAD+ -dependent ADP-ribosylation of
elongation factor 2, thereby inhibiting protein synthesis in eukaryotic
cells. Fragment B binds to the cell surface receptor and facilitates the
delivery of fragment A to the cytosol.
Sensitivity
The bacterium is sensitive to the majority of
antibiotics, such as the
penicillins,
ampicillin,
cephalosporins,
quinolones,
chloramphenicol,
tetracyclines,
cefuroxime, and
trimethoprim.
Genetics
The genome of
C. diphtheriae consists of a single circular chromosome of 2,5 Mbp, with no plasmids.
[2][3] The genome shows an extreme
compositional bias, being noticeably higher in G+C near the origin than at the terminus.
See also
References
- Nester, Eugene W. et al. (2004). Microbiology: A Human Perspective (Fourth ed.). Boston: McGraw-Hill. ISBN 0-07-247382-7.
- Cerdeño-Tárraga,
A. M.; Efstratiou, A; Dover, L. G.; Holden, M. T.; Pallen, M; Bentley,
S. D.; Besra, G. S.; Churcher, C; James, K. D.; De Zoysa, A;
Chillingworth, T; Cronin, A; Dowd, L; Feltwell, T; Hamlin, N; Holroyd,
S; Jagels, K; Moule, S; Quail, M. A.; Rabbinowitsch, E; Rutherford, K.
M.; Thomson, N. R.; Unwin, L; Whitehead, S; Barrell, B. G.; Parkhill, J
(2003). "The complete genome sequence and analysis of Corynebacterium diphtheriae NCTC13129". Nucleic acids research 31 (22): 6516–23. doi:10.1093/nar/gkg874. PMC 275568. PMID 14602910. edit
- Sangal, V; Tucker, N. P.; Burkovski, A; Hoskisson, P. A. (2012). "The
draft genome sequence of Corynebacterium diphtheriae bv. Mitis NCTC
3529 reveals significant diversity between the primary disease-causing
biovars". Journal of Bacteriology 194 (12): 3269. doi:10.1128/JB.00503-12. PMC 3370853. PMID 22628502. edit
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