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Journal of Bacteriology & ParasitologyA New Paradigm for Genus Mycobacterium Population Structure
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Journal of Biotechnology & BiomaterialsOptimization of Fermentation Conditions of the Engineered Corynebacterium Glutamicum to Enhance L-Ornithine Production by Response Surface Methodology
Corynebacterium (kôr"u-nē-bak-tēr'ē-um, ku-rin'u-) is a genus of Gram-positive, aerobe, rod-shaped bacteria. They are widely distributed in nature and are mostly innocuous. Some are useful in industrial settings such as C. glutamicum. Others can cause human disease. C. diphtheriae, for example, is the pathogen responsible for diphtheria.
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. Thanks to 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 the Greek corönë ("knotted rod") and bacterion ("rod"). The term "diphtheroids" is used to represent corynebacteria that are nonpathogenic; for example, C. diphtheriae would be excluded. The term, diphtheroid, comes from Greek diphthera- prepared hide, leather.
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 2 amino acid insertion in a conserved region of the enzyme phosphoribose diphosphate:decaprenyl-phosphate phosphoribosyltransferase and a 3 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 Dietzia species, 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 distinct clade, within which is a distinct subclade, cluster I. The cluster is made up of the species C. diptheriae, C. pseudotuberculosis, C. ulcerans, C. aurimucosum, C. glutamicumi and C. efficiens. This cluster is distinguished by several conserved signature indels, such as a 2 amino acid insertion in LepA and a 7 or 8 amino acid insertions in RpoC. There are also 21 conserved signature proteins which 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.
The principal features of the Corynebacterium genus were described by Collins and Cummins in 1986. They are Gram-positive, catalase positive, nonspore-forming, nonmotile, rod-shaped bacteria that are straight or slightly curved. Metachromatic granules are usually present representing stored phosphate regions. Their size falls between 2-6 micrometers in length and 0.5 micrometers in diameter. The bacteria group together in a characteristic way, which has been described as the form of a "V", "palisades", or "Chinese letters". They may also appear elliptical. They are aerobic or facultatively anaerobic, chemoorganotrophs, with a 51–65% genomic G:C content. They are pleomorphic through their life cycles; they occur in various lengths and frequently have thickenings at either end, depending on the surrounding conditions.
The cell wall is distinctive, with a predominance of meso-diaminopimelic acid in the murein wall and many repetitions of arabinogalactan as well as corynemycolic acid (a mycolic acid with 22 to 26 carbon atoms), tied together by disaccharide bonds called L-Rhap-(1 → 4)--D-GlcNAc-phosphate. These form a complex commonly seen in Corynebacterium species: the mycolyl-AG–peptidoglican (mAGP).
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 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).
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. 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. amicolatum, 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.
Role in disease
The most notable human infection is diphtheria, caused by Corynebacterium 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. It is an uncommon illness that tends to occur in unvaccinated individuals, especially school-aged children, those in developing countries, elderly, neutropenic or immunocompromised patients, and those with prosthetic devices such as prosthetic heart valves, shunts, or catheters. 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. C. tenuis is believed to cause trichomycosis palmellina and trichomycosis axillaris. C. striatum may cause axillary odor. C. minutissimum causes erythrasma.
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 (Khurana et al., 2000). 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. It is used in the foods industry as monosodium glutamate (MSG) 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 Corynebacterium 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 there is a build up of intermediates and therefore 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 (Sec) or the twin-arginine translocation pathway (Tat).
Most species of corynebacteria are not lipophilic.
The nonlipophilic bacteria may be classified as fermentative and nonfermentative:
- Fermentative corynebacteria
- Nonfermentative corynebacteria
- Corynebacterium jeikeium
- Corynebacterium urealyticum
- Corynebacterium afermentans subsp. lipophilum
- Corynebacterium accolens
- Corynebacterium macginleyi
- CDC coryneform groups F-1 and G
- Corynebacterium bovis
Novel corynebacteria that does not contain mycolic acids
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|40x40px||Wikispecies has information related to: Corynebacterium|
- Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9.
- Database of Corynebacterial Transcription Factors and Regulatory Networks
- Rollins, David M. University of Maryland: Pathogentic Microbiology: Corynebacterium 
- Burkovski A (editor). (2008). Corynebacteria: Genomics and Molecular Biology. Caister Academic Press. ISBN 1-904455-30-1. .