Editing Corynebacterium diphtheriae (section)

== Pathogenicity ==
{{Main|Diphtheria}}
[[File:Dirty white pseudomembrane classically seen in diphtheria 2013-07-06 11-07.jpg|upright=1.3|thumb|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.<ref name="pmid32003344"/>  ''C. diphtheriae'' is a rod-shaped, Gram-positive, non spore-forming, and nonmotile bacterium.<ref>{{Cite web|url=https://www.cdc.gov/diphtheria/index.html|title=Diphtheria Infection {{!}} Home {{!}} CDC|date=2017-04-10|website=www.cdc.gov|language=en-us|access-date=2017-11-27}}</ref>  ''C. diphtheriae'' has shown to exclusively infect humans. It is believed that humans may be the reservoir for this pathogen. However, there have been extremely rare cases in which ''C. diphtheriae'' has been found in animals. These infections were only toxigenic in two dogs and two horses.<ref>{{cite journal | vauthors = Tyler R, Rincon L, Weigand MR, Xiaoli L, Acosta AM, Kurien D, Ju H, Lingsweiler S, Prot EY | display-authors = 6 | title = Toxigenic Corynebacterium diphtheriae Infection in Cat, Texas, USA | journal = Emerging Infectious Diseases | volume = 28 | issue = 8 | pages = 1686–1688 | date = August 2022 | pmid = 35876749 | pmc = 9328917 | doi = 10.3201/eid2808.220018 }}</ref>

The disease occurs primarily in tropical regions and [[developing countries]]. Immunocompromised individuals, poorly immunized adults, and unvaccinated children are at the greatest risk of contracting diphtheria. Mode of transmission is person-to-person contact via respiratory droplets (i.e., coughing or sneezing). Less commonly, it could also be passed by touching open sores or contaminated surfaces. During the typical course of disease, the body region most commonly affected is the upper respiratory system. A thick, grey coating accumulates in the nasopharyngeal region, making breathing and swallowing more difficult. The disease remains contagious for at least two weeks following the disappearance of symptoms but has been known to last for up to a month.<ref>{{Cite news |url= https://medlineplus.gov/diphtheria.html |title=Diphtheria | work = MedlinePlus | publisher = U.S. National Library of Medicine |access-date=2017-11-27 }}</ref>

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. This could cause even more dangerous symptoms such as shortness of breath.<ref name=":2" /> 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).<ref name=":0">{{cite journal | vauthors = Hadfield TL, McEvoy P, Polotsky Y, Tzinserling VA, Yakovlev AA | title = The pathology of diphtheria | journal = The Journal of Infectious Diseases | volume = 181 | issue = Suppl 1 | pages = S116–S120 | date = February 2000 | pmid = 10657202 | doi = 10.1086/315551 | doi-access = free }}</ref>

The first step of ''C. diphtheriae'' infection involves the toxigenic bacteria colonizing a mucosal layer. In young children, this typically occurs in the upper respiratory tract mucosa. In adults, the infection is limited mostly to the tonsillar region. Some unusual sites of infection include the heart, larynx, trachea, bronchi, and anterior areas of the mouth including the buccal mucosa, the lips, tongue, and the hard and soft palate.<ref name="pmid31804499">{{cite journal | vauthors = Sharma NC, Efstratiou A, Mokrousov I, Mutreja A, Das B, Ramamurthy T | title = Diphtheria | journal = Nature Reviews. Disease Primers | volume = 5 | issue = 1 | pages = 81 | date = December 2019 | pmid = 31804499 | doi = 10.1038/s41572-019-0131-y | s2cid = 208737335 | doi-access = free }}</ref> The bacteria have several virulence factors to help them localize on areas of the respiratory tract, many of which are yet to be fully understood as diphtheria does not affect many model hosts such as mice. One common virulence factor that has been studied ''in vitro'' is DIP0733, a multi-functional protein that has been shown to have a role in bacterial adhesion to host cells and fibrogen-binding qualities. In experiments with mutant strains of the ''C. diphtheriae'', adhesion and epithelial infiltration decreased significantly. The ability to bind to extracellular matrices aids the bacteria in avoiding detection by the body's immune system.<ref>{{cite journal | vauthors = Antunes CA, Sanches dos Santos L, Hacker E, Köhler S, Bösl K, Ott L, de Luna M, Hirata R, Azevedo VA, Mattos-Guaraldi AL, Burkovski A | display-authors = 6 | title = Characterization of DIP0733, a multi-functional virulence factor of Corynebacterium diphtheriae | journal = Microbiology | volume = 161 | issue = Pt 3 | pages = 639–647 | date = March 2015 | pmid = 25635272 | doi = 10.1099/mic.0.000020 | doi-access = free }}</ref>

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.<ref name="pmid31804499"/>

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 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 colour and then later becomes dirty-grey and tough due to the necrotic epithelium.<ref name="pmid31804499"/>

Pseudomembrane formation on the trachea or bronchi will decrease the 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.<ref name="pmid31804499"/>