Corynebacterium

Corynebacterium (kôr"u-nē-bak-tēr'ē-um, ku-rin'u-) is a genus of Gram-positive rod-shaped bacteria. They are widely distributed in nature and are mostly innocuous.^[1] Some are useful in industrial settings such as C. glutamicum.^[2] Others can cause human disease. C. diphtheriae, for example, is the pathogen responsible for diphtheria.

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. Thanks to studies of 16S-rRNA, they have been grouped into the subdivision of Gram-positive eubacteria with high G:C content, with close philogenetic relationship to Arthrobacter, Mycobacterium, Nocardia, and Streptomyces.^[3] The term comes from the Greek corönë ("knotted rod") and bacterion ("rod"). The term "diphtheroids" is used to represent Corynebacteria that are non-pathogenic; for example, C. diphtheriae would be excluded.

Characteristics

The principal features of the Corynebacterium genus were described by Collins and Cummins in 1986.^[4] They are Gram-positive, catalase positive, non-spore-forming, non-motile, rod-shaped bacteria that are straight or slightly curved.^[5] 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 cycle: they come in various lengths and frequently have thickenings at either end, depending on the surrounding conditions.^[6]

Cell wall

The cell wall is distinctive, with a predominance of meso-diaminopimelic acid in the murein wall^[1][5] 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).^[7]

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.^[4] Some of the Corynebacterium 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.^[5] The color tends to be yellowish white in Loeffler's medium. In TSA, it 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

Corynebacteria species occur commonly in nature in the soil, water, plants, and food products.^[1][5] The non-diphtheiroid Corynebacterium can even be found in the mucosa and normal skin flora of humans and animals.^[1][5] 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.^[8] Other pathogenic species in humans include: C. amicolatum, C. striatum, C. jeikeium, C. urealyticum, and C. xerosis (Oteo et al., 2001; Lagrou et al., 1998; Boc & Martone, 1995);^[9][10] all of these are important as pathogens in immunosuppressed patients. Pathogenic species in other animals include C. bovis and C. renale.^[11]

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.^[12] It is an uncommon illness that tends to occur in unvaccinated individuals, especially school-aged children, those in developing countries,^[13] 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.^[14] 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.^[8]

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.^[15] C. tenuis is believed to cause trichomycosis palmellina and trichomycosis axillaris.^[16] C. striatum may cause axillary odor.^[17] C. minutissimum causes erythrasma.

Industrial Uses

Non-pathogenic species of Corynebacterium are used for very important industrial applications, such as the production of amino acids,^[18][19] nucleotides, and other nutritional factors (Martín, 1989); bioconversion of steroids;^[20] degradation of hydrocarbons;^[21] cheese aging;^[22] and production of enzymes (Khurana et al., 2000). Some species produce metabolites similar to antibiotics: bacteriocins of the corynecin-linocin type,^[14][23][24] anti-tumor agents,^[25] etc. One of the most studied species is C. glutamicum, whose name refers to its capacity to produce glutamic acid in aerobic conditions.^[26] 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 popular food additive that is made at a rate of 1.5 million tons/ year by Corynebacterium. The metabolic pathways of Corynebacterium have been further manipulated to produce lysine and threonine.

Expression of functionally active human epidermal growth factor has been done in C. glutamicum,^[27] 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).^[28]

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

Species

Most species of corynebacteria are non-lipophilic, but some are lipophilic.

Non-lipophilic

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 sp. ^[29]

• Nonfermentative Corynebacteria
  • Corynebacterium afermentans subsp. afermentans
  • Corynebacterium auris
  • Corynebacterium pseudodiphtheriticum
  • Corynebacterium propinquum^[29]

Lipophilic

• Corynebacterium jeikeium
• Corynebacterium urealyticum
• Corynebacterium afermentans subsp. lipophilum
• Corynebacterium accolens
• Corynebacterium macginleyi
• CDC coryneform groups F-1 and G
• Corynebacterium bovis^[29]

References

• 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 [2]

Further reading

• Burkovski A (editor). (2008). Corynebacteria: Genomics and Molecular Biology. Caister Academic Press. ISBN 1904455301. [3]. http://www.horizonpress.com/cory.