Corynebacterium

Corynebacterium
C. ulcerans colonies on a blood agar plate
Scientific classification
Kingdom:	Bacteria
Phylum:	Actinobacteria
Order:	Actinomycetales
Suborder:	Corynebacterineae
Family:	Corynebacteriaceae
Genus:	Corynebacterium Lehmann & Neumann 1896
Species
C. accolens C. afermentans C. ammoniagenes C. amycolatum C. argentoratense C. aquaticum C. auris C. bovis C. diphtheriae C. equi (now Rhodococcus equi) C. efficiens C. flavescens C. glucuronolyticum C. glutamicum C. granulosum C. haemolyticum C. halofytica C. kroppenstedtii C. jeikeium (group JK) C. macginleyi C. matruchotii C. minutissimum C. parvum (Propionibacterium acnes) C. paurometabolum C. propinquum C. pseudodiphtheriticum (C. hofmannii) C. pseudotuberculosis (C. ovis) C. pyogenes - Trueperella pyogenes C. urealyticum (group D2) C. renale C. resistens C. spec C. striatum C. tenuis C. ulcerans C. urealyticum C. xerosis

Corynebacterium (/kɔːrˈaɪnəbækˌtɪəriəm/, /kɔːrˈɪnə-/) 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.^[1] Some are useful in industrial settings such as C. glutamicum.^[2] 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.^[3]

The term comes from the Greek κορωνη, corönë ("knotted rod") and βακτηριον, bacterion ("rod"). The term "diphtheroids" is used to represent corynebacteria that are nonpathogenic; for example, C. diphtheriae would be excluded (reference?). The term diphtheroid comes from Greek διφθερα, diphthera—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 Dietzia genus, 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.^[4]

Characteristics

The principal features of the Corynebacterium genus were described by Collins and Cummins in 1986.^[5] They are gram-positive, catalase-positive, nonspore-forming, nonmotile, rod-shaped bacteria that are straight or slightly curved.^[6] 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 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 lifecycles, they occur in various lengths, and they frequently have thickenings at either end, depending on the surrounding conditions.^[7]

Cell wall

The cell wall is distinctive, with a predominance of mesodiaminopimelic acid in the murein wall^[1][6] 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-Rhap-(1 → 4)--D-GlcNAc-phosphate. These form a complex commonly seen in Corynebacterium species: the mycolyl-AG–peptidoglican (mAGP).^[8]

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.^[5] 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.^[6] 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.^[1][6] The nondiphtheiroid Corynebacterium species can even be found in the mucosa and normal skin flora of humans and animals.^[1][6] 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.^[9] Other pathogenic species in humans include: C. amicolatum, C. striatum, C. jeikeium, C. urealyticum, and C. xerosis;^[10][11] all of these are important as pathogens in immunosuppressed patients. Pathogenic species in other animals include C. bovis and C. renale.^[12]

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.^[13] 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^[14] It can occasionally infect wounds, the vulva, the conjunctiva, and the middle ear. It can be spread within a hospital.^[15] 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.^[9]

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.^[16] C. tenuis is believed to cause trichomycosis palmellina and trichomycosis axillaris.^[17] C. striatum may cause axillary odor.^[18] C. minutissimum causes erythrasma.

Industrial uses

Nonpathogenic species of Corynebacterium are used for very important industrial applications, such as the production of amino acids,^[19][20] nucleotides, and other nutritional factors (Martín, 1989); bioconversion of steroids;^[21] degradation of hydrocarbons;^[22] cheese aging;^[23] and production of enzymes (Khurana et al., 2000). Some species produce metabolites similar to antibiotics: bacteriocins of the corynecin-linocin type,^[15][24][25] antitumor agents,^[26] etc. One of the most studied species is C. glutamicum, whose name refers to its capacity to produce glutamic acid in aerobic conditions.^[27] 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 ^[28]

Expression of functionally active human epidermal growth factor has been brought about in C. glutamicum,^[29] 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.^[30]

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

Species

• Corynebacterium efficiens

Most species of corynebacteria are not lipophilic.

Nonlipophilic

The nonlipophilic bacteria may be classified as fermentative and nonfermentative:

• Fermentative corynebacteria
  • Corynebacterium diphtheriae group
  • Corynebacterium xerosis and Corynebacterium striatum
  • Corynebacterium minutissimum
  • Corynebacterium amycolatum
  • Corynebacterium glucuronolyticum
  • Corynebacterium argentoratense
  • Corynebacterium matruchotii
  • Corynebacterium glutamicum
  • Corynebacterium sp.^[31]
• Nonfermentative corynebacteria
  • Corynebacterium afermentans subsp. afermentans
  • Corynebacterium auris
  • Corynebacterium pseudodiphtheriticum
  • Corynebacterium propinquum^[31]

Lipophilic

• Corynebacterium jeikeium
• Corynebacterium urealyticum
• Corynebacterium afermentans subsp. lipophilum
• Corynebacterium accolens
• Corynebacterium macginleyi
• CDC coryneform groups F-1 and G
• Corynebacterium bovis^[31]

Novel corynebacteria that do not contain mycolic acids

• Corynebacterium kroppenstedtii^[32]

References

1. Collins MD, Hoyles L, Foster G, Falsen E (May 2004). "Corynebacterium caspium sp. nov., from a Caspian seal (Phoca caspica)". Int. J. Syst. Evol. Microbiol. 54 (Pt 3): 925–8. doi:10.1099/ijs.0.02950-0. PMID 15143043.
2. Burkovski A (editor). (2008). Corynebacteria: Genomics and Molecular Biology. Caister Academic Press. ISBN 1-904455-30-1. .
3. Woese CR (June 1987). "Bacterial evolution". Microbiol. Rev. 51 (2): 221–71. PMC 373105. PMID 2439888.
4. Gao, B.; Gupta, R. S. (2012). "Phylogenetic Framework and Molecular Signatures for the Main Clades of the Phylum Actinobacteria". Microbiology and Molecular Biology Reviews. 76 (1): 66–112. doi:10.1128/MMBR.05011-11. PMC 3294427. PMID 22390973.
5. Collins, M. D. & Cummins, C. S. (1986). Genus Corynebacterium Lehmann and Neumann 1896, 350AL. In Bergey's Manual of Systematic Bacteriology, vol. 2, pp. 1266–1276. Edited by P. H. A. Sneath, N. S. Mair, M. E. Sharpe & J. G. Holt. Baltimore: Williams & Wilkins.
6. Yassin AF, Kroppenstedt RM, Ludwig W (May 2003). "Corynebacterium glaucum sp. nov". Int. J. Syst. Evol. Microbiol. 53 (Pt 3): 705–9. doi:10.1099/ijs.0.02394-0. PMID 12807190.
7. Keddie RM, Cure GL (April 1977). "The cell wall composition and distribution of free mycolic acids in named strains of coryneform bacteria and in isolates from various natural sources". J. Appl. Bacteriol. 42 (2): 229–52. doi:10.1111/j.1365-2672.1977.tb00689.x. PMID 406255.
8. Seidel M, Alderwick LJ, Sahm H, Besra GS, Eggeling L (February 2007). "Topology and mutational analysis of the single Emb arabinofuranosyltransferase of Corynebacterium glutamicum as a model of Emb proteins of Mycobacterium tuberculosis". Glycobiology. 17 (2): 210–9. doi:10.1093/glycob/cwl066. PMID 17088267.
9. Costa JJ, Michel JL, Rappuoli R, Murphy JR (October 1981). "Restriction map of corynebacteriophages beta c and beta vir and physical localization of the diphtheria tox operon". J. Bacteriol. 148 (1): 124–30. PMC 216174. PMID 6270058.
10. (Oteo et al., 2001; Lagrou et al., 1998; Boc & Martone, 1995);Kono M, Sasatsu M; Aoki, T (1983). "R plasmids in Corynebacterium xerosis strains". Antimicrob. Agents Chemother. 23: 506–8. doi:10.1128/aac.23.3.506.
11. Pitcher DG (1983). "Deoxyribonucleic acid base composition of Corynebacterium diphtheriae and corynebacteria with cell wall type IV". FEMS Microbiol. Lett. 16 (2–3): 291–5. doi:10.1111/j.1574-6968.1983.tb00305.x.
12. Watts y col., 2001; Hirsbrunner G et al. Nephrectomy for chronic, unilateral suppurative pyleonephritis in cattle. Tierarztl Prax, 1996 Feb, 24(1), 17 - 21; [Nephrectomy_for_chronic_unilateral_suppurative_pyleonephritis_in_cattle]
13. MedlinePlus - Difteria
14. IIZUKA, Hideyo; FURUTA, Joana Akiko; OLIVEIRA, Edison P. Tavares de. (1980). "Diphtheria: immunity in an infant population in the city of S. Paulo, SP, Brazil". Rev. Saúde Pública. 14 (4): 462–8. doi:10.1590/S0034-89101980000400005. ISSN 0034-8910.
15. Kerry-Williams SM, Noble WC (October 1986). "Plasmids in group JK coryneform bacteria isolated in a single hospital". J Hyg (Lond). 97 (2): 255–63. doi:10.1017/S0022172400065347. PMC 2083551. PMID 3023480.
16. Cristóbal Leóna; Javier Ariza (2004). "Guías para el tratamiento de las infecciones relacionadas con catéteres intravasculares de corta permanencia en adultos: conferencia de consenso SEIMC-SEMICYUC". Enferm Infecc Microbiol Clin. 22 (2): 92–101. doi:10.1157/13056889. PMID 14756991.
17. Trichomycosis axilarris at eMedicine
18. Natsch, A.; Gfeller, H.; Gygax, P.; Schmid, J. (2005). "Isolation of a bacterial enzyme releasing axillary malodor and its use as a screening target for novel deodorant formulations1". International Journal of Cosmetic Science. 27 (2): 115–22. doi:10.1111/j.1467-2494.2004.00255.x. PMID 18492161.
19. Hongo, M., Oki, T. and Ogata, S. (1972). "Phage contamination and control". In K. Yamada; S Kinoshita; T. Tsunoda; K. Aida. The Microbial Production of Amino Acids. New York: John Wiley. pp. 63–83.
20. Yamada, K., Kinoshita, S., Tsunoda, T. and Aida, K. 1972. The Microbial Production of Amino Acids. Wiley, New York.
21. Constantinides A (January 1980). "Steroid transformation at high substrate concentrations using immobilized Corynebacterium simplex cells". Biotechnol. Bioeng. 22 (1): 119–36. doi:10.1002/bit.260220110. PMID 7350926.
22. Cooper DG, Zajic JE, Gracey DE (February 1979). "Analysis of corynomycolic acids and other fatty acids produced by Corynebacterium lepus grown on kerosene". J. Bacteriol. 137 (2): 795–801. PMC 218359. PMID 422512.
23. Lee CW, Lucas S, Desomazeaud MJ (1985). "Phenylalanine and tyrosine catabolism in some cheese coryneform bacteria". FEMS Microbiol. Lett. 26 (2): 201–5. doi:10.1111/j.1574-6968.1985.tb01591.x.
24. Kerry-Williams SM, Noble WC (1984). "Plasmid associated bacteriocin production in a JK-type coryneform bacterium". FEMS Microbiol. Lett. 25 (2–3): 179–182. doi:10.1111/j.1574-6968.1984.tb01451.x.
25. Suzuki T, Honda H, Katsumata R (1972). "Production of antibacterial compounds analogous to chloramphenicol by n-paraffin-grown bacteria". Agr. Biol. Chem. 36 (12): 2223–8. doi:10.1271/bbb1961.36.2223.
26. Milas L, Scott MT (1978). "Antitumor activity of Corynebacterium parvum". Adv. Cancer Res. Advances in Cancer Research. 26: 257–306. doi:10.1016/S0065-230X(08)60090-1. ISBN 978-0-12-006626-1. PMID 343523.
27. Abe, S., Takayama, K. and Kinoshita, S. (1967). "Taxonomical studies on glutamic acid-producing bacteria". J. Gen. Appl. Microbiol. 13 (3): 279–301. doi:10.2323/jgam.13.279.
28. Kjeldsen, K. 2008. Optimization of an industrial L-lysine producing corynebacterium glutamicum strain. Research paper. Center for microbial biotechnology department of systems biology technical University of Denmark.
29. Date M, Yokoyama K, Umezawa Y, Matsui H, Kikuchi Y (January 2006). "Secretion of human epidermal growth factor by Corynebacterium glutamicum." Lett Appl Microbiol. 42 (1): 66-70.
30. Meissner D, Vollstedt A, van Dijl JM, Freudl R (September 2007). "Comparative analysis of twin-arginine (Tat)-dependent protein secretion of a heterologous model protein (GFP) in three different gram-positive bacteria." Appl Microbiol Biotechnol. 76 (3): 633-42.
31. Until this point in list the ref is: Funke G, von Graevenitz A, Clarridge JE, Bernard KA (January 1997). "Clinical microbiology of coryneform bacteria". Clin. Microbiol. Rev. 10 (1): 125–59. PMC 172946. PMID 8993861.
32. Collins M. D.; Falsen E.; Åkervall E.; Sjöden B.; Alvarez A. (1998). "Corynebacterium kroppenstedtii sp. nov., a novel corynebacterium that does not contain mycolic acids". International Journal of Systematic Bacteriology. 48 (4): 1449–1454. doi:10.1099/00207713-48-4-1449.

• 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

Further reading

• Burkovski A (editor). (2008). Corynebacteria: Genomics and Molecular Biology. Caister Academic Press. ISBN 1-904455-30-1. .