Corynebacterium diphtheriae

Corynebacterium diphtheriae
	Corynebacterium diphtheriae
Systematics
Department :	Actinobacteria
Order :	Actinomycetales
Subordination :	Corynebacterineae
Family :	Corynebacteriaceae
Genre :	Corynebacterium
Type :	Corynebacterium diphtheriae
Scientific name
	Corynebacterium diphtheriae
	( Kruse 1886) Lehmann & Neumann 1896

The bacterium Corynebacterium diphtheriae is the causative agent of diphtheria . It is also known as the Klebs-Loeffler bacillus because it was discovered in 1884 by Edwin Klebs (1834–1913) and Friedrich Loeffler (1852–1915). The bacterium forms a toxin ( diphtheria toxin ), which is what makes it dangerous.

morphology

Corynebacterium diphtheriae is a gram-positive , facultatively anaerobic , club-shaped bacterium. The cell wall contains mycolic acids . Because it has no flagella , it is immobile. Most of the tribes have pili . It does not form capsules or spores . With the Neisser staining , characteristic terminal swellings of polyphosphates and calcium, which are called polar bodies, can be shown. Under the microscope, the individual rods (length up to 5 µm, thickness 0.8 µm) are often V- or Y-shaped and are reminiscent of Chinese characters. For studies it is important that the Corynebacteria can be divided into biotypes based on the average number of polar bodies .

Biotype	Number of polar bodies
Corynebacterium diphtheriae mitis	5 to 6
Corynebacterium diphtheriae gravis	1 to 2
Corynebacterium diphtheriae intermedius	3 to 4

Epidemiology

Because humans are the only pathogen reservoir, the spread of the bacterium can be combated very well with vaccinations. While there were 3 million diseases in World War II , the incidence is very low today. In Central Europe it is approx. 0.001 / 100,000 / year. In the first years after the end of the USSR , there was a massive increase in the number of diseases in the successor states when vaccination programs collapsed. Today, however , C. diphtheriae is again successfully combated there by means of large-scale vaccination campaigns. However, diphtheria remains a problem in many developing countries .

Pathogenesis

The transmission occurs through close contact (face-to-face) with infected people, mostly through droplets, more rarely also through contaminated objects. The pathogen enters the body through the mucous membrane, conjunctiva or wounds and multiplies there. Diphtheria toxin, which is not produced by all strains of C. diphtheriae , locally damages the epithelial cells so that a pseudomembrane is formed in the nasopharynx. This thick, gray coating consists of a fibrin network in which dead cell components, bacteria and leukocytes are stored. The tissue under the pseudomembrane is necrotic . If the pseudomembrane spreads to the larynx , it can cause severe shortness of breath and ultimately death. The poison also works throughout the body, primarily damaging the heart , kidneys , adrenal glands , motor nerves and liver . Skin infections and endocarditis have also been observed regardless of the effects of the poison .

Diphtheria toxin

The genetic information for the toxin tox + is not a priori in the genome of C. diphtheriae , but in a virus, the so-called prophage beta. The gene is transduced into the bacterial genome . The “cooperation” of these genes is so close that the dtxR gene , which regulates tox + , can be found on the bacterial genome . In the presence of iron, dtxR switches off the production of the poison.

Similar to other AB bacterial toxins , the spherical diphtheria toxin consists of a larger B part and a smaller A part. The B part contains a binding site with which it connects to a receptor ( HB-EGF-precursor - heparin-binding epidermal growth factor , dt .: heparin- binding precursor of the epidermal growth factor EGF ), which is often found on human cells, binds. The HB-EGF precursor is particularly abundant in the cell membranes of heart, nerve or kidney cells, which explains why these cells in particular prefer to take up the toxin. The poison is then taken up in an endocytic vacuole in the cell, where it is Toxin unfolds at a pH of 5. As a result, hydrophobic components appear, which insert into the membrane of the vacuole. The A portion of the toxin is exposed to the cytoplasm of the cell and cleaved. On the A part there is an enzyme that transfers an ADP-ribosyl to the elongation factor eEF2 of NAD ⁺ . This inhibits the elongation factor, protein biosynthesis can no longer take place and ultimately the cell dies. The diphtheria toxin is so potent that one molecule is enough to kill a cell.

The detection is carried out by means of real-time PCR , followed by confirmation by means of an electrical test .

cultivation

In the laboratory may C. diphtheriae at 37 ° C on blood agar and serum-containing culture media or Hoyle agar grown are (normal atmosphere containing 10% CO ₂ addition). A nutrient medium made from Löffler's serum enables good growth and forms the characteristic morphology.

Visible colonies form after 18-24 hours at temperatures of 15–40 ° C. Since tellurite is reduced to tellurium by the bacteria and enriched intracellularly, media containing tellurite color the colonies black over time. Concentrations above 100 mg / ml have an inhibitory effect on other bacteria from the pharyngeal flora so that C. diphtheriae can be identified selectively; However, no conclusions can be drawn about toxin formation.

Biochemical investigations enable species differentiation, alternatively this is done via MALDI-TOF .

Reporting requirement

In Germany the suspicion of an illness, the illness diphtheria and the death from it as well as in particular are notifiable according to § 6 . Likewise, the direct or indirect detection of toxin-forming Corynebacteria is notifiable by name in accordance with Section 7 of the Infection Protection Act , if the evidence indicates an acute infection.

In Austria, diphtheria is a notifiable disease in accordance with Section 1 (1) of the 1950 Epidemic Act . The reporting obligation relates to cases of illness and death.

In Switzerland, the clinical suspicion of the disease diphtheria and the initiation of a pathogen-specific laboratory diagnosis and a positive laboratory analysis result (or a negative result in a test for the toxin gene) for the pathogen Corynebacterium diphtheriae (and other toxin-producing corynebacteria ) must be reported ( according to the epidemic law) EpG) in connection with the Epidemics Ordinance and Annex 1 or Annex 3 of the Ordinance of the FDHA on the reporting of observations of communicable diseases in humans .

literature

RR MacGregor: Corynebacterium diphtheriae. In: Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 6th edition. 2005.
Marlies Höck and Helmut Hahn: Corynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 309 ff .

Web links

Commons : Corynebacterium diphtheriae - Collection of images, videos and audio files

CoryneRegNet - Database of Corynebacterial Transcription Factors and Regulatory Networks

Individual evidence

^ ^A ^b Friedrich Hofmann: Diphtheria. In: Heinz Spiess, Ulrich Heininger, Wolfgang Jilg (Eds.): Impfkompendium . 8th edition. Georg Thieme Verlag, 2015, ISBN 978-3-13-498908-3 , p. 148 ff .
↑ ^a ^b ^c Marlies Höck and Helmut Hahn: Korynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 309 , doi : 10.1007 / 978-3-662-48678-8_37 .
↑ ^a ^b ^c Marlies Höck and Helmut Hahn: Korynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 310 , doi : 10.1007 / 978-3-662-48678-8_37 .
↑ ^a ^b ^c Marlies Höck and Helmut Hahn: Korynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 312 , doi : 10.1007 / 978-3-662-48678-8_37 .
↑ ^a ^b ^c ^d Marlies Höck and Helmut Hahn: Corynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 313 , doi : 10.1007 / 978-3-662-48678-8_37 .

[:0-1] A ^b Friedrich Hofmann: Diphtheria. In: Heinz Spiess, Ulrich Heininger, Wolfgang Jilg (Eds.): Impfkompendium . 8th edition. Georg Thieme Verlag, 2015, ISBN 978-3-13-498908-3 , p. 148 ff .

[:2-2] Marlies Höck and Helmut Hahn: Korynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 309 , doi : 10.1007 / 978-3-662-48678-8_37 .

[:1-3] Marlies Höck and Helmut Hahn: Korynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 310 , doi : 10.1007 / 978-3-662-48678-8_37 .

[:4-4] Marlies Höck and Helmut Hahn: Korynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 312 , doi : 10.1007 / 978-3-662-48678-8_37 .

[:3-5] Marlies Höck and Helmut Hahn: Corynebacteria . In: Sebastian Suerbaum, Gerd-Dieter Burchard, Stefan HE Kaufmann, Thomas F. Schulz (eds.): Medical microbiology and infectious diseases . Springer-Verlag, 2016, ISBN 978-3-662-48678-8 , pp. 313 , doi : 10.1007 / 978-3-662-48678-8_37 .