Corynebacterium

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.[5]

The term comes from Greek κορύνη, korýnē 'club, mace, staff, knobby plant bud or shoot'[6] and βακτήριον, baktḗrion 'little rod'.[7] 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, diphthérā 'prepared hide, leather'.[8][9]

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. diptheriae, 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.[10] Corynebateria have a high G+C content ranging from 46-74 mol%.[11]

The principal features of the genus Corynebacterium were described by Collins and Cummins in 1986.[12] They are gram-positive, catalase-positive, non-spore-forming, non-motile, rod-shaped bacteria that are straight or slightly curved.[13] 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.[14]

Corynebacterium species occur commonly in nature in the soil, water, plants, and food products.[2][13] The nondiphtheiroid Corynebacterium species can even be found in the mucosa and normal skin flora of humans and animals.[2][13] Unusual habitats, such as the preen gland of birds have been recently reported for Corynebacterium uropygiale.[16] 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.[17] Other pathogenic species in humans include: C. amycolatum, C. striatum, C. jeikeium, C. urealyticum, and C. xerosis;[18][19][20][21][22] all of these are important as pathogens in immunosuppressed patients. Pathogenic species in other animals include C. bovis and C. renale.[23] This genus has been found to be part of the human salivary microbiome.[24]

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.[25] 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[26] It can occasionally infect wounds, the vulva, the conjunctiva, and the middle ear. It can be spread within a hospital.[27] 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.[17]

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.[28] C. tenuis is believed to cause trichomycosis palmellina and trichomycosis axillaris.[29] C. striatum may cause axillary odor.[30] C. minutissimum causes erythrasma.

Nonpathogenic species of Corynebacterium are used for very important industrial applications, such as the production of amino acids,[31][32] nucleotides, and other nutritional factors (Martín, 1989); bioconversion of steroids;[33] degradation of hydrocarbons;[34] cheese aging;[35] and production of enzymes.[36] Some species produce metabolites similar to antibiotics: bacteriocins of the corynecin-linocin type,[27][37][38] antitumor agents,[39] etc. One of the most studied species is C. glutamicum, whose name refers to its capacity to produce glutamic acid in aerobic conditions.[40] 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.[41]

Expression of functionally active human epidermal growth factor has been brought about in C. glutamicum,[42] 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.[43]

Unlike gram-negative bacteria, the gram-positive Corynebacterium species lack lipopolysaccharides that function as antigenic endotoxins in humans.

• Corynebacterium efficiens

Most species of corynebacteria are not lipophilic.

• Burkovski, Andreas, ed. (2008). Corynebacteria: Genomics and Molecular Biology. Caister Academic Press. ISBN 978-1-904455-30-1.
• Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 978-0-8385-8529-0.CS1 maint: extra text: authors list (link)
• Database of Corynebacterial Transcription Factors and Regulatory Networks
• Rollins, David M. University of Maryland: Pathogentic Microbiology: Corynebacterium
• A. Khamis, D. Raoult, B. La Scola. 2004. rpoB gene sequencing for identification of Corynebacterium species. Journal of Clinical Microbiology. 42(9):3925–3931.
• A. Poetsch, U. Haußmann, A. Burkovski. 2011. Proteomics of corynebacteria: From biotechnology workhorses to pathogens. Proteomics 2011(11):3244–3255. Available from: https://doi.org/10.1002/pmic.201000786
• D. Goldenberger et al. 2014. Extended characterization of Corynebacterium pyruviciproducens based on clinical strains from Canada and Switzerland. Journal of Clinical Microbiology. 52(9), 3180–3183.
• E. Hacker et al. 2015. Colonization of human epithelial cell lines by Corynebacterium ulcerans from human and animal sources. [Internet].  Microbiology (United Kingdom). 161(8):1582–1591. Available from: https://doi.org/10.1099/mic.0.000121
• K. A. Bernard, C. Munro, D. Wiebe, E. Ongsanso. 2002., Characteristics of rare or recently described Corynebacterium species recovered from human clinical material in Canada. Journal of Clinical Microbiology. 40(11):4375–4381.
• M. Bittel, S. Gastiger, B. Amin, J. Hofmann, A. Burkovski. 2018. Surface and Extracellular Proteome of the Emerging Pathogen Corynebacterium ulcerans. Proteomes. 6(2):18. Available from: https://doi.org/10.3390/proteomes6020018
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• N. Hansmeier, T. C. Chao, J. Kalinowski, A. Pühler, A. Tauch. 2006. Mapping and comprehensive analysis of the extracellular and cell surface proteome of the human pathogen Corynebacterium diphtheriae. [Internet] Proteomics 2006(6):2465–2476. Available from: https://doi.org/10.1002/pmic.200500360
• P. Riegel, R. Ruimy, R. Christen, H. Monteil. 1996. Species identities and antimicrobial susceptibilities of Corynebacteria isolated from various clinical sources. European Journal of Clinical Microbiology and Infectious Diseases. 15(8), 657–662.
• Riegel P, Ruimy R, Christen R, Monteil H. 1996. Species identities and antimicrobial susceptibilities of corynebacteria isolated from various clinical sources. [Internet] European Journal of Clinical Microbiology & Infectious Diseases: Official Publication of the European Society of Clinical Microbiology. 15(8):657-62. Available from: https://search.proquest.com/docview/78481820?accountid=10355
• V. Carfora et al. 2018. Non-toxigenic Corynebacterium ulcerans sequence types 325 and 339 isolated from two dogs with ulcerative lesions in Italy. [Internet] Journal of Veterinary Diagnostic Investigation. 30(3):447–450. Available from: https://doi.org/10.1177%2F1040638718764786
• Y. Nishio et al. 2007. Evolutionary process of amino acid biosynthesis in Corynebacterium at the whole genome level. [Internet]. Molecular Biology and Evolution. 21(9):1683–1691. Available from: https://doi.org/10.1093/molbev/msh175