Corynebacterium

Corynebacterium () is a genus of bacteria that are Gram-positive and aerobic. They are bacilli (rod-shaped), and in some phases of life they are, more particularly, club-shaped, which inspired the genus name ("coryneform" means "club-shaped").
They are widely distributed in nature in the microbiota of animals (including the human microbiota) and are mostly innocuous, most commonly existing in commensal relationships with their hosts. Some are useful in industrial settings such as "C. glutamicum". Others can cause human disease, including most notably diphtheria, which is caused by "C. diphtheriae". As with various species of a microbiota (including their cousins in the genera "Arcanobacterium" and "Trueperella"), they usually are not pathogenic but can occasionally opportunistically capitalize on atypical access to tissues (via wounds) or weakened host defenses.
Taxonomy.
The genus "Corynebacterium" was created by Lehmann and Neumann in 1896 as a taxonomic group to contain the bacterial rods responsible for causing diphtheria. The genus was defined based on morphological characteristics. Based on studies of 16S-rRNA, they have been grouped into the subdivision of gram-positive eubacteria with high G:C content, with close phylogenetic relationship to "Arthrobacter", "Mycobacterium", "Nocardia", and "Streptomyces".
The term comes from Greek κορύνη, ' 'club, mace, staff, knobby plant bud or shoot' and βακτήριον, ' 'little rod'. The term "diphtheroids" is used to represent corynebacteria that are non-pathogenic; for example, "C. diphtheriae" would be excluded. The term diphtheroid comes from Greek διφθέρα, "" 'prepared hide, leather'.
Genomics.
Comparative analysis of corynebacterial genomes has led to the identification of several conserved signature indels which are unique to the genus. Two examples of these conserved signature indels are a two-amino-acid insertion in a conserved region of the enzyme phosphoribose diphosphate:decaprenyl-phosphate phosphoribosyltransferase and a three-amino-acid insertion in acetate kinase, both of which are found only in "Corynebacterium" species. Both of these indels serve as molecular markers for species of the genus "Corynebacterium". Additionally, 16 conserved signature proteins, which are uniquely found in "Corynebacterium" species, have been identified. Three of the conserved signature proteins have homologs found in the genus "Dietzia", which is believed to be the closest related genus to "Corynebacterium". In phylogenetic trees based on concatenated protein sequences or 16S rRNA, the genus "Corynebacterium" forms a distinct clade, within which is a distinct subclade, cluster I. The cluster is made up of the species "C. diphtheriae, C. pseudotuberculosis, C. ulcerans, C. aurimucosum, C. glutamicum," and "C. efficiens". This cluster is distinguished by several conserved signature indels, such as a two-amino-acid insertion in LepA and a seven- or eight-amino-acid insertions in RpoC. Also, 21 conserved signature proteins are found only in members of cluster I. Another cluster has been proposed, consisting of "C. jeikeium" and "C. urealyticum", which is supported by the presence of 19 distinct conserved signature proteins which are unique to these two species. Corynebateria have a high G+C content ranging from 46-74 mol%.
Characteristics.
The principal features of the genus "Corynebacterium" were described by Collins and Cummins in 1986. They are gram-positive, catalase-positive, non-spore-forming, non-motile, rod-shaped bacteria that are straight or slightly curved. Metachromatic granules are usually present representing stored phosphate regions. Their size falls between 2 and 6 μms in length and 0.5 μm in diameter. The bacteria group together in a characteristic way, which has been described as the form of a "V", "palisades", or "Chinese characters". They may also appear elliptical. They are aerobic or facultatively anaerobic, chemoorganotrophs. They are pleomorphic through their lifecycles, they occur in various lengths, and they frequently have thickenings at either end, depending on the surrounding conditions.
Cell wall.
The cell wall is distinctive, with a predominance of mesodiaminopimelic acid in the murein wall and many repetitions of arabinogalactan, as well as corynemycolic acid (a mycolic acid with 22 to 26 carbon atoms), bound by disaccharide bonds called L-Rha"p"-(1 → 4)--D-GlcNAc-phosphate. These form a complex commonly seen in "Corynebacterium" species: the mycolyl-AG–peptidoglican (mAGP).
Culture.
Corynebacteria grow slowly, even on enriched media. In terms of nutritional requirements, all need biotin to grow. Some strains also need thiamine and PABA. Some of the "Corynebacterium" species with sequenced genomes have between 2.5 and 3.0 million base pairs. The bacteria grow in Loeffler's medium, blood agar, and trypticase soy agar (TSA). They form small, grayish colonies with a granular appearance, mostly translucent, but with opaque centers, convex, with continuous borders. The color tends to be yellowish-white in Loeffler's medium. In TSA, they can form grey colonies with black centers and dentated borders that look similar to flowers ("C. gravis"), or continuous borders ("C. mitis"), or a mix between the two forms ("C. intermedium").
Habitat.
"Corynebacterium" species occur commonly in nature in the soil, water, plants, and food products. The nondiphtheiroid "Corynebacterium" species can even be found in the mucosa and normal skin flora of humans and animals. Unusual habitats, such as the preen gland of birds have been recently reported for "Corynebacterium uropygiale". Some species are known for their pathogenic effects in humans and other animals. Perhaps the most notable one is "C. diphtheriae", which acquires the capacity to produce diphtheria toxin only after interacting with a bacteriophage. Other pathogenic species in humans include: "C. amycolatum", "C. striatum", "C. jeikeium", "C. urealyticum", and "C. xerosis"; all of these are important as pathogens in immunosuppressed patients. Pathogenic species in other animals include "C. bovis" and "C. renale". This genus has been found to be part of the human salivary microbiome.
Role in disease.
The most notable human infection is diphtheria, caused by "C. diphtheriae". It is an acute and contagious infection characterized by pseudomembranes of dead epithelial cells, white blood cells, red blood cells, and fibrin that form around the tonsils and back of the throat. In developed countries, it is an uncommon illness that tends to occur in unvaccinated individuals, especially school-aged children, elderly, neutropenic or immunocompromised patients, and those with prosthetic devices such as prosthetic heart valves, shunts, or catheters. It is more common in developing countries It can occasionally infect wounds, the vulva, the conjunctiva, and the middle ear. It can be spread within a hospital. The virulent and toxigenic strains are lysogenic, and produce an exotoxin formed by two polypeptide chains, which is itself produced when a bacterium is transformed by a gene from the β prophage.
Several species cause disease in animals, most notably "C. pseudotuberculosis", which causes the disease caseous lymphadenitis, and some are also pathogenic in humans. Some attack healthy hosts, while others tend to attack the immunocompromised. Effects of infection include granulomatous lymphadenopathy, pneumonitis, pharyngitis, skin infections, and endocarditis. Corynebacterial endocarditis is seen most frequently in patients with intravascular devices. Several species of "Corynebacterium" can cause trichomycosis axillaris. "C. striatum" may cause axillary odor. "C. minutissimum" causes erythrasma.
Industrial uses.
Nonpathogenic species of "Corynebacterium" are used for very important industrial applications, such as the production of amino acids, nucleotides, and other nutritional factors (Martín, 1989); bioconversion of steroids; degradation of hydrocarbons; cheese aging; and production of enzymes. Some species produce metabolites similar to antibiotics: bacteriocins of the corynecin-linocin type, antitumor agents, etc. One of the most studied species is "C. glutamicum", whose name refers to its capacity to produce glutamic acid in aerobic conditions. This is used in the food industry as monosodium glutamate in the production of soy sauce and yogurt.
Species of "Corynebacterium" have been used in the mass production of various amino acids including glutamic acid, a food additive that is made at a rate of 1.5 million tons/ year. The metabolic pathways of "Corynebacterium " have been further manipulated to produce lysine and threonine.
L-Lysine production is specific to "C. glutamicum" in which core metabolic enzymes are manipulated through genetic engineering to drive metabolic flux towards the production of NADPH from the pentose phosphate pathway, and L-4-aspartyl phosphate, the commitment step to the synthesis of L-lysine, lysC, dapA, dapC, and dapF. These enzymes are up-regulated in industry through genetic engineering to ensure adequate amounts of lysine precursors are produced to increase metabolic flux. Unwanted side reactions such as threonine and asparagine production can occur if a buildup of intermediates occurs, so scientists have developed mutant strains of" C. glutamicum" through PCR engineering and chemical knockouts to ensure production of side-reaction enzymes are limited. Many genetic manipulations conducted in industry are by traditional cross-over methods or inhibition of transcriptional activators.
Expression of functionally active human epidermal growth factor has been brought about in "C. glutamicum", thus demonstrating a potential for industrial-scale production of human proteins. Expressed proteins can be targeted for secretion through either the general secretory pathway or the twin-arginine translocation pathway.
Unlike gram-negative bacteria, the gram-positive "Corynebacterium" species lack lipopolysaccharides that function as antigenic endotoxins in humans.
Species.
Most species of corynebacteria are not lipophilic.
Nonlipophilic.
The nonlipophilic bacteria may be classified as fermentative and nonfermentative: