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free encyclopedia species of prokaryote corynebacterium diphtheriae scientific classification domain bacteria kingdom bacillati phylum actinomycetota class actinomycetes order mycobacteriales family corynebacteriaceae genus corynebacterium species c diphtheriae binomial name corynebacterium diphtheriae kruse 1886 lehmann and neumann 1896 approved lists 1980 1 corynebacterium diphtheriae a is a gram positive pathogenic bacterium that causes diphtheria 2 it is also known as the klebs löffler bacillus because it was discovered in 1884 by german bacteriologists edwin klebs 1834 1913 and friedrich löffler 1852 1915 3 while nontoxigenic c diphtheriae may rarely produce systemic disease by invading tissues 4 virulence is enhanced when the bacteria are infected by a bacteriophage carrying a gene which gives rise to a toxin 5 this toxin causes the disease 6 diphtheria is caused by the adhesion and infiltration of the bacteria into the mucosal layers of the body primarily affecting the respiratory tract and causing the subsequent release of an exotoxin 7 the toxin has a localized effect on skin lesions as well as a metastatic proteolytic effects on other organ systems in severe infections 7 originally a major cause of childhood mortality respiratory diphtheria has become rare in the united states by the vigorous administration of diphtheria vaccines starting in 1914 8 9 the incidence of diphtheria has decreased since the development of a toxoid vaccine in 1923 10 although diphtheria outbreaks continue to occur this is often in developing countries where the majority of the population is not vaccinated 11 12 cutaneous diphtheria skin lesions infected by toxigenic c diphtheriae 4 are prevalent in tropical climates and may contribute to diphtheria outbreaks 13 10 classification edit 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 all may be either toxigenic and therefore cause diphtheria or not toxigenic strain subtyping involves comparing species of bacteria and categorizing them into subspecies 14 strain subtyping also helps with identifying the origin of a certain bacteria s outbreak however when it comes to the subtyping of c diphtheriae there is not a lot of useful or accurate classification due to the lack of publicly available resources to identify strains and therefore find the origin of outbreaks 15 corynebacterium diphtheriae is part of the c diphtheriae species complex which also includes c belfantii c pseudotuberculosis c rouxii c silvaticum c ulcerans 16 and c ramonii 17 toxin edit main article diphtheria toxin c diphtheriae produces the 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 that are toxigenic are ones which have been infected with a bacteriophage 18 19 the diphtheria toxin gene is encoded by a corynephage found in toxigenic strains integrated into the bacterial chromosome in the lysogenic phase of the bacteriophage 20 the diphtheria toxin repressor is mainly controlled by iron it serves as the essential cofactor for the activation of target dna binding 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 21 elek s test for toxigenicity is used to determine whether the organism is able to produce the diphtheria toxin 22 diphtheria toxin can also be produced by certain strains of corynebacterium ulcerans and corynebacterium pseudotuberculosis which are zoonotic pathogens 13 6 as well as other phage infected members of the c diphtheriae complex 16 17 identification edit to identify c diphtheriae a gram stain is performed to show gram positive highly pleomorphic organisms often looking like chinese letters stains such as 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 or volutin granules known under the eponymous name babes ernst granules after their inventors paul ernst and victor babes an enrichment medium such as löffler s medium preferentially grows 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 colourimetrically indicated by brown colonies for most corynebacterium species or by a black halo around the c diphtheriae colonies the organism produces catalase but not urease which differentiates it from corynebacterium ulcerans c diphtheriae does not produce pyrazinamidase which differentiates from corynebacterium striatum and corynebacterium jeikeium 23 pathogenicity edit main article diphtheria 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 6 c diphtheriae is a rod shaped gram positive non spore forming and nonmotile bacterium 24 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 25 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 26 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 27 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 7 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 28 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 29 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 28 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 28 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 28 transmission edit 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 15 vaccine edit a vaccine dtap effectively prevents the disease and is mandatory in the united states for participation in public education and some professions exceptions apply the invention of the toxoid vaccine which provides protection against corynebacterium diphtheriae caused a dramatic shift in the bacterium s rate of infection in the united states even though the vaccine was first made in the early 1800s it did not become widely available until the early 1910s according to the national health and nutrition examination survey nhanes 80 per cent of persons age 12 to 19 years were immune to diphtheria due to the wide use of the vaccine in the united states 30 diagnosis edit main article diphtheria diagnosis of respiratory c diphtheriae is made based on presentation clinically whereas non respiratory diphtheria may not be clinically suspected therefore laboratory testing is more reliant culturing is the most accurate kind of testing that will confirm or deny the prevalence of diphtheria toxins the testing is done by swabbing the possibly infected area as well as any lesions and sores 31 treatment and prevention edit main article diphtheria when a toxigenic strain of corynebacterium diphtheriae infects the human body it releases harmful toxins especially to the throat antitoxins are used to prevent further harm antibiotics are also used to fight the infection typical antibiotics that are used against diphtheria involve penicillin or erythromycin people infected with diphtheria must quarantine for at least 48 hours after being prescribed antibiotics to confirm that the person is no longer contagious tests are performed ensure that the bacteria have been cleared people are then vaccinated to prevent further transmission of the disease 32 the wide use of the diphtheria vaccine dramatically decreased the rate of infection and allows for primary prevention of the disease most people receive a 3 in 1 vaccine that consists of protection against diphtheria tetanus and pertussis which is commonly known as the dtap or tdap vaccine dtap vaccine is for children while the tdap vaccine is known for adolescents and adults 11 in the united states the dtap vaccine to parents of infants which typically involves a series of five shots is recommended these vaccines are injected through the arm or thigh and are administered when the infant is 2 months 4 months 6 months 15 18 months and then 4 6 years old 11 possible side events that are associated with the diphtheria vaccine include mild fever fussiness drowsiness or tenderness at the injection site although it is rare the dtap vaccine may cause an allergic reaction that causes hives or a rash to breakout within minutes of administering the vaccine 11 genetics edit the genome of c diphtheriae consists of a single circular chromosome of 2 5 mbp with no plasmids 33 its genome shows an extreme compositional bias being noticeably higher in g c near the origin than at the terminus 27 the corynebacterium diphtheriae genome is a single circular chromosome that has no plasmids these chromosomes have a high g c content which is what contributes to their high genetic diversity the high content of guanine and cytosine is not constant across the entire genome of the bacteria there is a terminus of replication around the 740kb region that causes a decrease in the g c content in other bacteria it is often seen that the g c content gets smaller near the terminus but c diphtheriae is a considerably strong genome that has this occurrence chromosomal replication is one of the ways this happens within this genome 27 notes edit pronunciation k ɔː ˈ r aɪ n ə b æ k t ɪər i ə m d ɪ f ˈ θ ɪər i i r ɪ n ə references edit parte ac corynebacterium lpsn hoskisson pa june 2018 microbe profile corynebacterium diphtheriae an old foe always ready to seize opportunity microbiology 164 6 865 867 doi 10 1099 mic 0 000627 pmc 6097034 pmid 29465341 barksdale l december 1970 corynebacterium diphtheriae and its relatives bacteriological reviews 34 4 378 422 doi 10 1128 br 34 4 378 422 1970 pmc 378364 pmid 4322195 1 2 mahesh m le t 2025 cutaneous diphtheria a potential lurking public health crisis annals of internal medicine clinical cases 4 9 doi 10 7326 aimcc 2025 0549 s2cid 281365405 ott l möller j burkovski a march 2022 interactions between the re emerging pathogen corynebacterium diphtheriae and host cells international journal of molecular sciences 23 6 3298 doi 10 3390 ijms23063298 pmc 8952647 pmid 35328715 1 2 muthuirulandi sethuvel dp subramanian n pragasam ak inbanathan fy gupta p johnson j et al 2019 insights to the diphtheria toxin encoding prophages amongst clinical isolates of corynebacterium diphtheriae from india indian journal of medical microbiology 37 3 423 425 doi 10 4103 ijmm ijmm_19_469 pmid 32003344 1 2 3 hadfield tl mcevoy p polotsky y tzinserling va yakovlev aa february 2000 the pathology of diphtheria the journal of infectious diseases 181 suppl 1 s116 s120 doi 10 1086 315551 pmid 10657202 national museum of american history the antibody initiative diphtheria treatments and prevention smithsonian retrieved 17 january 2026 tiwari ts wharton m 2018 19 diphtheria toxoid in plotkin sa orenstein wa offit pa edwards km eds plotkin s vaccines seventh ed elsevier pp 261 275 doi 10 1016 b978 0 323 35761 6 0001...