Corynebacterium diphtheriae

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 strains which are toxigenic are ones which have been infected with a bacteriophage.[5][6]

The diphtheria toxin gene is encoded by the bacteriophage found in toxigenic strains, integrated into the bacterial chromosome.[7] To accurately identify C. diphtheriae, a Gram stain is performed to show Gram-positive, highly pleomorphic organisms with no particular arrangement. Special stains like Albert's stain and Ponder's stain are used to demonstrate the metachromatic granules formed in the polar regions. The granules are called polar granules, Babes Ernst granules or volutin granules. 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 colorimetrically indicated by brown colonies for most Cornyebacterium 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 aporepressor shuts down toxin production.[8] Elek's test for toxigenicity is used to determine whether the organism is able to produce the diphtheria toxin.[9]

An adherent, dense, grey pseudomembrane covering the tonsils is classically seen in diphtheria.

Corynebacterium diphtheriae is the bacterium that causes the disease called diphtheria. Bacteriophages introduce a gene into the bacterial cells that makes a strain toxigenic. The strains that are not infected with these viruses are harmless.[4] C. diphtheriae is a rod-shaped, Gram-positive, nonspore-forming, and nonmotile bacterium.[10] C. diphtheriae has shown to exclusively infect humans. It is believed that humans may be the reservoir for this pathogen. However, there has been extremely rare cases in which C. diphtheriae has been found in animals. These infections were only toxigenic in 2 dogs and 2 horses.[11]

The disease occurs primarily in tropical regions and underdeveloped countries. Immunocompromised individuals, poorly immunized adults, and unvaccinated children are at the greatest risk for contracting diphtheria. Mode of transmission is person-to-person contact via respiratory droplets (i.e., coughing or sneezing), and less commonly, by touching open sores or contaminated surfaces. During the typical course of disease, the only affected body region is the upper respiratory system. A thick, gray coating accumulates in the nasopharyngeal region, making breathing and swallowing more difficult. The disease remains contagious for at least two weeks following disappearance of symptoms, but has been known to last for up to a month.[12]

The most common routes of entry for C. diphtheriae are the nose, tonsils, and throat. Individuals suffering from the disease may experience sore throat, weakness, fever, and swollen glands. If left untreated, diphtheria toxin may enter the bloodstream, causing damage to the kidneys, nerves, and heart. Extremely rare complications include suffocation and partial paralysis. A vaccine, DTaP, effectively prevents the disease and is mandatory in the United States for participation in public education and some professions (exceptions apply).[13] The first step of C. diphtheriae infection involves the toxigenic bacteria colonising a mucosal layer. In young children, this typically occurs in the upper respiratory tract mucosa. In adults, faucial diphtheria is more common wherein the primary site of infection is typically the posterior mouth or upper pharynx region. Some unusual sites of infection include the heart, larynx, trachea, bronchi, and anterior areas of the mouth including the buccal mucosa, the lips, the tongue, and the hard and soft palate.[14]

The diphtheritic lesion is often covered by a pseudomembrane composed of fibrin, bacterial cells, 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.[14]

Once the bacteria have localized in one area, they start multiplying and create the inflammatory pseudomembrane. Individuals with faucial diphtheria typically have the pseudomembrane grow over the tonsil and accessory structures, uvula, soft palate, and possibly also the nasopharyngeal area. In upper respiratory tract diphtheria, the pseudomembrane can grow on the pharynx, larynx, trachea, and bronchi/bronchioles. The pseudomembrane starts off white in color and then later becomes dirty-gray and tough due to the necrotic epithelium.[14]

Psuedomembrane formation on the trachea or bronchi will decrease efficiency of airflow. Over time, the diffusion rate in the alveoli decreases due to the lower airflow and decreases the partial pressure of oxygen in the systemic circulation, which can cause cyanosis and suffocation.[14]

The bacterium is sensitive to the majority of antibiotics, such as the penicillins, ampicillin, cephalosporins, quinolones, chloramphenicol, tetracyclines, cefuroxime, and trimethoprim.

The genome of C. diphtheriae consists of a single circular chromosome of 2.5 Mbp, with no plasmids.[15] Its genome shows an extreme compositional bias, being noticeably higher in G+C near the origin than at the terminus.

The Corynebacterium diphtheriae genome is a single circular chromosome that has no plasmids. These chromosomes have a high G+C content.

• Cutaneous diphtheria
• Diphtheria vaccine

• CoryneRegNet—Database of Corynebacterial Transcription Factors and Regulatory Networks
• Corynebacterium diphtheriae genome
• Type strain of Corynebacterium diphtheriae at BacDive - the Bacterial Diversity Metadatabase