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==Overview==
==Overview==
'''''Corynebacterium diphtheriae''''' is a pathogenic [[bacterium]] that causes [[diphtheria]]. It is also known as the '''Klebs-Löffler bacillus''', because it was discovered in 1884 by Germany|German [[Bacteriology|bacteriologists]] Edwin Klebs (1834 – 1912) and Friedrich Löffler (1852 – 1915).
''Corynebacterium diphtheriae'' is a pathogenic [[bacterium]] that causes [[diphtheria]]. It is a [[Facultative anaerobic organism|facultatively anaerobic]], [[Gram positive]] organism, characterized by non-encapsulated, non-sporulated, immobile, straight or curved rods. The [[genome]] of ''C. diphtheriae'' contains 2,488,635 [[nucleotides]], 2,389 [[genes]], and  69 structural [[RNA]] genes. [[Gram-stain]] will result in a blue-purple coloration due to containing [[polymetaphosphate]] [[granules]]. Many strains of ''C. diphtheriae'' produce [[diphtheria toxin]], a [[protein|protein]] [[exotoxin]], with a molecular weight of 62 [[Dalton (unit)|kilodaltons]] which ADP-ribosylates host [[Elongation factor|EF-2]], resulting in the inhibition of protein synthesis and producing signs of [[diphtheria]]. ''C. diptheriae'' is exclusively pathogenic in humans. ''C. diphtheriae'' can be classified into following four subspecies: ''mitis'', ''intermedius'', ''gravis'', and ''belfanti''. Diagnosis of''C. diphtheriae'' includes a [[Gram stain]] procedure; results will indicate [[gram-positive]], pleomorphic [[bacteria]] that will dye violet-blue and resemble clubs. ''C.diphtheriae'' causes [[diphtheria]] disease in non-immunized human hosts via secreted toxins. Toxigenic strains of the [[bacterium]] will secrete toxins in [[nasopharyngeal]] or skin [[lesions]]; it is common for hosts to carry ''C. diphtheriae'' in the [[nasopharyngeal]] region without displaying symptoms. [[Lysogenic]] conversion of nontoxigenic-toxigenic phenotypes of the [[bacterium]] can occur following transmission, allowing non-human/affected hosts to transmit [[diphtheria]] to humans. C. diphtheriae'' is sensitive to [[antibiotic]] therapy.


==Morphology and toxin production==
==Morphology and Structure==
''C. diphtheriae'' is a [[Facultative anaerobic organism|facultatively anaerobic]], [[Gram positive]] organism, characterized by non-encapsulated, non-sporulated, immobile, straight or curved rods with a length of 1 to 8 µm and width of 0.3 to 0.8 µm, which form ramified aggregations in culture (looking like "Chinese characters"). The bacterium may contain polymetaphosphate aggregates called Volutin granules. It is pathogenic only in humans.
*''C. diphtheriae'' is a [[Facultative anaerobic organism|facultatively anaerobic]], [[Gram positive]] organism, characterized by non-encapsulated, non-sporulated, immobile, straight or curved rods.<ref name="pmid21413281">{{cite journal |vauthors=Baron S, Murphy JR |title=Medical Microbiology |journal= |volume=4 |issue= |pages= |year=1996 |pmid=21413281 |doi= |url=}}</ref><ref name="pmid106070"></ref>
 
*The [[genome]] of ''C. diphtheriae'' contains 2,488,635 [[nucleotides]], 2,389 [[genes]], and  69 structural [[RNA]] genes.<ref name="Cerdeno-Tarraga2003">{{cite journal|last1=Cerdeno-Tarraga|first1=A. M.|title=The complete genome sequence and analysis of Corynebacterium diphtheriae NCTC13129|journal=Nucleic Acids Research|volume=31|issue=22|year=2003|pages=6516–6523|issn=1362-4962|doi=10.1093/nar/gkg874}}</ref>
Many strains of ''C. diphtheriae'' produce [[diphtheria toxin]], a [[protein|proteic]] [[exotoxin]], with a molecular weight of 62 [[Dalton (unit)|kilodaltons]] which ADP-ribosylates host [[Elongation factor|EF-2]], which results in the inhibition of protein synthesis and thus is responsible for the signs of diphtheria. The inactivation of this toxin with an antitoxic serum ([[antitoxin]]) is the basis of the antidiphtheric [[vaccination]]. However, not all strains are toxigenic; the ability to produce the exotoxin is conferred on the bacterium when it is infected by a [[bacteriophage]] (a mechanism termed "lysogenic activation"). A non-toxigenic strain can thus become toxigenic by the infection of such a bacteriophage.<ref>{{cite book |last=Nester |first=Eugene W. |year=2004 |title=Microbiology: A Human Perspective |edition=Fourth |location=Boston |publisher=McGraw-Hill |isbn=0-07-247382-7 |display-authors=etal}}</ref>
**As a [[gram-positive]] bacteria, ''C. diphtheriae'' contains a [[cell membrane]] and a [[lipid]]-rich [[murein]] layer outside.
*[[Cell wall]] sugars of ''C. diphtheriae'' include [[arabinose]], [[galactose]], and [[mannose]].
*[[Gram-stain]] will result in a blue-purple coloration due to containing [[polymetaphosphate]] [[granules]].
*Many strains of ''C. diphtheriae'' produce [[diphtheria toxin]], a [[protein|protein]] [[exotoxin]], with a molecular weight of 62 [[Dalton (unit)|kilodaltons]] which ADP-ribosylates host [[Elongation factor|EF-2]], resulting in the inhibition of protein synthesis and producing signs of [[diphtheria]].<ref>{{cite book |last=Nester |first=Eugene W. |year=2004 |title=Microbiology: A Human Perspective |edition=Fourth |location=Boston |publisher=McGraw-Hill |isbn=0-07-247382-7 |display-authors=etal}}</ref>
**The inactivation of this toxin with an antitoxic serum ([[antitoxin]]) is the basis of the antidiphtheric [[vaccination]].
***Not all strains are toxigenic; the ability to produce the [[exotoxin]] is conferred on the bacterium when it is infected by a [[bacteriophage]] through a mechanism termed [[lysogenic]] activation.  
***A non-toxigenic strain can become toxigenic by the infection of such a bacteriophage.
*''C. diptheriae'' is exclusively pathogenic in humans.<ref name="pmid1749380">{{cite journal |vauthors=von Behring E, Kitasato S |title=[The mechanism of diphtheria immunity and tetanus immunity in animals. 1890] |language=German |journal=Mol. Immunol. |volume=28 |issue=12 |pages=1317, 1319–20 |year=1991 |pmid=1749380 |doi= |url=}}</ref>


==Classification==
==Classification==
Three subspecies are recognized: ''C. diphtheriae mitis'', ''C. diphtheriae intermedius'', and ''C. diphtheriae gravis''. The three subspecies differ slightly in their ability to metabolize certain nutrients, but all may be toxigenic (and therefore cause diphtheria) or non-toxigenic.
''C. diphtheriae'' can be classified into the following four subspecies:<ref name="pmid21413281">{{cite journal |vauthors=Baron S, Murphy JR |title=Medical Microbiology |journal= |volume=4 |issue= |pages= |year=1996 |pmid=21413281 |doi= |url=}}</ref><ref name="pmid106070">{{cite journal |vauthors=Chang DN, Laughren GS, Chalvardjian NE |title=Three variants of Corynebacterium diphtheriae subsp. mitis (Belfanti) isolated from a throat specimen |journal=J. Clin. Microbiol. |volume=8 |issue=6 |pages=767–8 |year=1978 |pmid=106070 |pmc=275340 |doi= |url=}}</ref>
*''C. diphtheriae mitis''
*''C. diphtheriae intermedius''
*''C. diphtheriae gravis''
*''C. diphtheriea belfanti''<ref name="urlPinkbook | Diphtheria | Epidemiology of Vaccine Preventable Diseases | CDC">{{cite web |url=http://www.cdc.gov/vaccines/pubs/pinkbook/dip.html |title=Pinkbook &#124; Diphtheria &#124; Epidemiology of Vaccine Preventable Diseases &#124; CDC |format= |work= |accessdate=}}</ref>


==Diagnosis==
==Diagnosis==
*Diagnosis of''C. diphtheriae'' includes a [[Gram stain]] procedure.
**Results will indicate [[gram-positive]], pleomorphic [[bacteria]] that will dye violet-blue and resemble clubs.<ref name="urlPinkbook | Diphtheria | Epidemiology of Vaccine Preventable Diseases | CDC">{{cite web |url=http://www.cdc.gov/vaccines/pubs/pinkbook/dip.html |title=Pinkbook &#124; Diphtheria &#124; Epidemiology of Vaccine Preventable Diseases &#124; CDC |format= |work= |accessdate=}}</ref>
*Additional tests include Albert's stain and Loeffler's stain.
*''C. diphtheriae'' should be cultured on an erichment medium, namely to allow it to overgrow any other organisms present in the specimen.<ref>{{cite book |last=Nester |first=Eugene W. |year=2004 |title=Microbiology: A Human Perspective |edition=Fourth |location=Boston |publisher=McGraw-Hill |isbn=0-07-247382-7 |display-authors=etal}}</ref>
**A selective plate [[tellurite agar]] which allows all ''Corynebacteria'' (including ''C. diphtheriae'') to reduce tellurite to metallic tellurium and produce brown colonies
***''C. diphtheriae'' is the only [[corynebacterium]] that will produce a black halo around the colonies.


In order to accurately identify ''C. diphtheriae'', a [[Gram stain]] is performed to show gram-positive, highly pleomorphic organisms with no particular arrangement (resembling chinese letters). Then, culture the organism on an erichment medium, namely Löffler's serum, to allow it to overgrow any other organisms present in the specimen. After that, use a selective plate known as [[tellurite agar]] which allows all ''Corynebacteria'' (including ''C. diphtheriae'') to reduce tellurite to metallic tellurium producing brown colonies and, only in the case of ''C. diphtheriae'', a black halo around the colonies allowing for easy differentation of the organism.  
==Pathophysiology==
 
*''C.diphtheriae'' causes [[diphtheria]] disease in non-immunized human hosts via secreted toxins.<ref name="pmid21413281">{{cite journal |vauthors=Baron S, Murphy JR |title=Medical Microbiology |journal= |volume=4 |issue= |pages= |year=1996 |pmid=21413281 |doi= |url=}}</ref><ref name="pmid106070">
It's worth noting that a low concentration of iron is required in the medium for toxin production; as at high iron concentrations, iron molecules bind to a [[repressor]] which shuts down toxin production<ref>Microbiology: A Human Perspective. Fourth edition. McGraw Hill</ref>. This is most appreciated when performing [[Elek's test]] for toxogenecity, in order to know if the organism is able to produce the diphtheria toxin or not.
**Toxigenic strains of the [[bacterium]] will secrete toxins in [[nasopharyngeal]] or skin [[lesions]]; it is common for hosts to carry ''C. diphtheriae'' in the [[nasopharyngeal]] region without displaying symptoms.
**A low concentration of iron is required in the medium for toxin production; at high iron concentrations, iron molecules bind to a [[repressor]] which shuts down toxin production<ref>{{cite book |last=Nester |first=Eugene W. |year=2004 |title=Microbiology: A Human Perspective |edition=Fourth |location=Boston |publisher=McGraw-Hill |isbn=0-07-247382-7 |display-authors=etal}}</ref>
*''C.diphtheriae'' is transmitted through [[respiratory]] droplets, secretions, or direct contact.
*[[Lysogenic]] conversion of nontoxigenic-toxigenic phenotypes of the [[bacterium]] can occur following transmission, allowing non-human/affected hosts to transmit [[diphtheria]] to humans.


==Sensitivity==
==Sensitivity==
The bacterium is sensitive to the majority of [[antibiotics]], such as the [[penicillin]]s, [[ampicillin]], [[cephalosporin]]s, [[quinolone]]s, [[chloramphenicol]], [[tetracycline]]s, [[cefuroxime]] and [[trimethoprim]].
''C. diphtheriae'' is sensitive to the following antibiotics:<ref name="pmid4627747">{{cite journal |vauthors=Zamiri I, McEntegart MG |title=The sensitivity of diphtheria bacilli to eight antibiotics |journal=J. Clin. Pathol. |volume=25 |issue=8 |pages=716–7 |year=1972 |pmid=4627747 |pmc=477485 |doi= |url=}}</ref>
==Genetics==
*[[Benzylpenicillin]]
The genome of ''C. diphtheriae'' consists of a single circular chromosome of 2,5 Mbp, with no plasmids.<ref name="pmid14602910">{{cite journal| author=Cerdeño-Tárraga AM, Efstratiou A, Dover LG, Holden MT, Pallen M, Bentley SD et al.| title=The complete genome sequence and analysis of Corynebacterium diphtheriae NCTC13129. | journal=Nucleic Acids Res | year= 2003 | volume= 31 | issue= 22 | pages= 6516-23 | pmid=14602910 | doi= | pmc=275568 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14602910  }} </ref><ref name="pmid22628502">{{cite journal| author=Sangal V, Tucker NP, Burkovski A, Hoskisson PA| title=The draft genome sequence of Corynebacterium diphtheriae bv. mitis NCTC 3529 reveals significant diversity between the primary disease-causing biovars. | journal=J Bacteriol | year= 2012 | volume= 194 | issue= 12 | pages= 3269 | pmid=22628502 | doi=10.1128/JB.00503-12 | pmc=3370853 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22628502  }} </ref>
*[[Ampicillin]]
 
*[[Oxytetracycline]]
==References==
*[[Erythromycin]]
<references/>
*Cephaloradine
*[[Lincomycin]]
*[[Clindamycin]]
*[[Neomycin]]


==External links==
==External links==
* [https://www.cebitec.uni-bielefeld.de/groups/gi/software/coryneregnet/ CoryneRegNet] - Database of Corynebacterial Transcription Factors and Regulatory Networks''
* [https://www.cebitec.uni-bielefeld.de/groups/gi/software/coryneregnet/ CoryneRegNet] - Database of Corynebacterial Transcription Factors and Regulatory Networks''


==References==
{{reflist|2}}


 
[[Category:Infectious Disease]]


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Revision as of 15:55, 13 October 2016

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This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Diphtheria.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Luke Rusowicz-Orazem, B.S.

Corynebacterium diphtheriae
Gram stained Corynebacterium diphtheriae culture
Gram stained Corynebacterium diphtheriae culture
Scientific classification
Kingdom: Bacteria
Phylum: Actinobacteria
Order: Actinomycetales
Family: Corynebacteriaceae
Genus: Corynebacterium
Species: C. diphtheriae
Binomial name
Corynebacterium diphtheriae
Kruse, 1886

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Overview

Corynebacterium diphtheriae is a pathogenic bacterium that causes diphtheria. It is a facultatively anaerobic, Gram positive organism, characterized by non-encapsulated, non-sporulated, immobile, straight or curved rods. The genome of C. diphtheriae contains 2,488,635 nucleotides, 2,389 genes, and 69 structural RNA genes. Gram-stain will result in a blue-purple coloration due to containing polymetaphosphate granules. Many strains of C. diphtheriae produce diphtheria toxin, a protein exotoxin, with a molecular weight of 62 kilodaltons which ADP-ribosylates host EF-2, resulting in the inhibition of protein synthesis and producing signs of diphtheria. C. diptheriae is exclusively pathogenic in humans. C. diphtheriae can be classified into following four subspecies: mitis, intermedius, gravis, and belfanti. Diagnosis ofC. diphtheriae includes a Gram stain procedure; results will indicate gram-positive, pleomorphic bacteria that will dye violet-blue and resemble clubs. C.diphtheriae causes diphtheria disease in non-immunized human hosts via secreted toxins. Toxigenic strains of the bacterium will secrete toxins in nasopharyngeal or skin lesions; it is common for hosts to carry C. diphtheriae in the nasopharyngeal region without displaying symptoms. Lysogenic conversion of nontoxigenic-toxigenic phenotypes of the bacterium can occur following transmission, allowing non-human/affected hosts to transmit diphtheria to humans. C. diphtheriae is sensitive to antibiotic therapy.

Morphology and Structure

Classification

C. diphtheriae can be classified into the following four subspecies:[1][2]

  • C. diphtheriae mitis
  • C. diphtheriae intermedius
  • C. diphtheriae gravis
  • C. diphtheriea belfanti[6]

Diagnosis

  • Diagnosis ofC. diphtheriae includes a Gram stain procedure.
  • Additional tests include Albert's stain and Loeffler's stain.
  • C. diphtheriae should be cultured on an erichment medium, namely to allow it to overgrow any other organisms present in the specimen.[7]
    • A selective plate tellurite agar which allows all Corynebacteria (including C. diphtheriae) to reduce tellurite to metallic tellurium and produce brown colonies
      • C. diphtheriae is the only corynebacterium that will produce a black halo around the colonies.

Pathophysiology

  • C.diphtheriae causes diphtheria disease in non-immunized human hosts via secreted toxins.[1]
  • C.diphtheriae is transmitted through respiratory droplets, secretions, or direct contact.
  • Lysogenic conversion of nontoxigenic-toxigenic phenotypes of the bacterium can occur following transmission, allowing non-human/affected hosts to transmit diphtheria to humans.

Sensitivity

C. diphtheriae is sensitive to the following antibiotics:[8]

External links

  • CoryneRegNet - Database of Corynebacterial Transcription Factors and Regulatory Networks

References

  1. 1.0 1.1 1.2 Baron S, Murphy JR (1996). "Medical Microbiology". 4. PMID 21413281.
  2. 2.0 2.1 Chang DN, Laughren GS, Chalvardjian NE (1978). "Three variants of Corynebacterium diphtheriae subsp. mitis (Belfanti) isolated from a throat specimen". J. Clin. Microbiol. 8 (6): 767–8. PMC 275340. PMID 106070.
  3. Cerdeno-Tarraga, A. M. (2003). "The complete genome sequence and analysis of Corynebacterium diphtheriae NCTC13129". Nucleic Acids Research. 31 (22): 6516–6523. doi:10.1093/nar/gkg874. ISSN 1362-4962.
  4. Nester, Eugene W.; et al. (2004). Microbiology: A Human Perspective (Fourth ed.). Boston: McGraw-Hill. ISBN 0-07-247382-7.
  5. von Behring E, Kitasato S (1991). "[The mechanism of diphtheria immunity and tetanus immunity in animals. 1890]". Mol. Immunol. (in German). 28 (12): 1317, 1319–20. PMID 1749380.
  6. 6.0 6.1 "Pinkbook | Diphtheria | Epidemiology of Vaccine Preventable Diseases | CDC".
  7. Nester, Eugene W.; et al. (2004). Microbiology: A Human Perspective (Fourth ed.). Boston: McGraw-Hill. ISBN 0-07-247382-7.
  8. Zamiri I, McEntegart MG (1972). "The sensitivity of diphtheria bacilli to eight antibiotics". J. Clin. Pathol. 25 (8): 716–7. PMC 477485. PMID 4627747.


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