Corynebacterium

''Corynebacterium'' () is a genus of Gram-positive bacteria and most are aerobic. They are bacilli (rod-shaped), and in some phases of life they are, more specifically, 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, such as '' C. glutamicum'', are commercially and industrially useful. Others can cause human disease, including, most notably, diphtheria, which is caused by '' C. diphtheriae''. Like various species of microbiota (including their relatives in the genera '' Arcanobacterium'' and '' Trueperella''), they are usually not pathogenic, but can occasionally capitalize opportunistically 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 relationships 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 (CSIs) that are unique to the genus. Two examples of CSIs 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 these 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. Corynebacteria 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, for Coryn Taylor 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 μm 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.

Some corynebacteria are lipophilic (such as CDC coryneform groups F-1 and G, '' C. accolens'', '' C. afermentans'' subsp. ''lipophilum'', '' C. bovis'', '' C. jeikeium'', '' C. macginleyi'', '' C. uropygiale'', and '' C. urealyticum''), but medically relevant corynebacteria are typically not. The nonlipophilic bacteria may be classified as fermentative (such as '' C. amycolatum''; '' C. argentoratense'', members of the '' C. diphtheriae'' group, '' C. glucuronolyticum'', '' C. glutamicum'', '' C. matruchotii'', '' C. minutissimum'', '' C. striatum'', and '' C. xerosis'') or nonfermentative (such as '' C. afermentans'' subsp. ''afermentans'', '' C. auris'', '' C. pseudodiphtheriticum'', and '' C. propinquum'').

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). Unlike most corynebacteria, '' Corynebacterium kroppenstedtii'' does not contain mycolic acids.

Culture

Corynebacteria grow slowly, even on enriched media. In 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 either resemble flowers (''C. gravis''), continuous borders (''C. mitis''), or a mix between the two forms (''C. intermedium'').

Habitat

''Corynebacterium'' species occur commonly in nature in soil, water, plants, and food products. The non-diphtheroid ''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, 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 produce an exotoxin formed by two polypeptide chains, which is itself produced when a bacterium is transformed by a gene from the β prophage.SIB
Viral exotoxin
Expasy: ViralZone. Accessed 2 Feb 2021

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 important industrial applications, such as the production of amino acids and nucleotides, 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.

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, , , and . 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

''Corynebacterium'' comprises the following species:

* '' C. accolens'' Neubauer et al. 1991

* '' C. afermentans'' Riegel et al. 1993
* '' C. alimapuense'' Claverias et al. 2019
* "'' C. alkanolyticum''" Lee and Reichenbach 2006
* '' C. ammoniagenes'' (Cooke and Keith 1927) Collins 1987
* '' C. amycolatum'' Collins et al. 1988
* '' C. anserum'' Liu et al. 2021
* '' C. appendicis'' Yassin et al. 2002

* '' C. aquatimens'' Aravena-Román et al. 2012
* '' C. aquilae'' Fernández-Garayzábal et al. 2003
* '' C. argentoratense'' Riegel et al. 1995
* "'' C. asperum''" De Briel et al. 1992
* '' C. atrinae'' Kim et al. 2015
* '' C. atypicum'' Hall et al. 2003
* '' C. aurimucosum'' Yassin et al. 2002
* '' C. auris'' Funke et al. 1995
* '' C. auriscanis'' Collins et al. 2000

* '' C. belfantii'' Dazas et al. 2018

* '' C. beticola'' Abdou 1969 (Approved Lists 1980)

* "'' C. bouchesdurhonense''" Ndongo et al. 2017
* "'' C. bouchesdurhonense''" Lo et al. 2019
* '' C. bovis'' Bergey et al. 1923 (Approved Lists 1980)
* '' C. callunae'' (Lee and Good 1963) Yamada and Komagata 1972 (Approved Lists 1980)
* '' C. camporealensis'' Fernández-Garayzábal et al. 1998
* '' C. canis'' Funke et al. 2010
* '' C. capitovis'' Collins et al. 2001
* '' C. casei'' Brennan et al. 2001
* '' C. caspium'' Collins et al. 2004

* '' C. choanae'' Busse et al. 2019

* '' C. ciconiae'' Fernández-Garayzábal et al. 2004
* '' C. comes'' Schaffert et al. 2021
* '' C. confusum'' Funke et al. 1998
* '' C. coyleae'' Funke et al. 1997
* '' C. crudilactis'' Zimmermann et al. 2016

* '' C. cystitidis'' Yanagawa and Honda 1978 (Approved Lists 1980)
* "'' C. defluvii''" Yu et al. 2017
* "'' C. dentalis''" Benabdelkader et al. 2020
* '' C. deserti'' Zhou et al. 2012
* '' C. diphtheriae'' (Kruse 1886) Lehmann and Neumann 1896 (Approved Lists 1980)
* '' C. doosanense'' Lee et al. 2009
* '' C. durum'' Riegel et al. 1997
* '' C. efficiens'' Fudou et al. 2002
* '' C. endometrii'' Ballas et al. 2020

* '' C. epidermidicanis'' Frischmann et al. 2012

* '' C. faecale'' Chen et al. 2016
* '' C. falsenii'' Sjödén et al. 1998

* '' C. felinum'' Collins et al. 2001

* '' C. flavescens'' Barksdale et al. 1979 (Approved Lists 1980)
* '' C. fournieri'' corrig. Diop et al. 2018

* '' C. frankenforstense'' Wiertz et al. 2013
* '' C. freiburgense'' Funke et al. 2009
* '' C. freneyi'' Renaud et al. 2001

* '' C. gerontici'' Busse et al. 2019

* '' C. glaucum'' Yassin et al. 2003
* '' C. glucuronolyticum'' Funke et al. 1995
* '' C. glutamicum'' (Kinoshita et al. 1958) Abe et al. 1967 (Approved Lists 1980)
* '' C. glyciniphilum'' (ex Kubota et al. 1972) Al-Dilaimi et al. 2015

* '' C. gottingense'' Atasayar et al. 2017

* '' C. guangdongense'' Li et al. 2016

* "'' C. haemomassiliense''" Boxberger et al. 2020
* '' C. halotolerans'' Chen et al. 2004
* '' C. hansenii'' Renaud et al. 2007
* '' C. heidelbergense'' Braun et al. 2021
* '' C. hindlerae'' Bernard et al. 2021

* '' C. humireducens'' Wu et al. 2011

* "'' C. ihumii''" Padmanabhan et al. 2014
* '' C. ilicis'' Mandel et al. 1961 (Approved Lists 1980)
* '' C. imitans'' Funke et al. 1997
* "'' C. incognitum''" Boxberger et al. 2021

* '' C. jeddahense'' Edouard et al. 2017
* '' C. jeikeium'' Jackman et al. 1988
* '' C. kalinowskii'' Schaffert et al. 2021
* "'' C. kefirresidentii''" Blasche et al. 2017
* '' C. kroppenstedtii'' Collins et al. 1998
* '' C. kutscheri'' (Migula 1900) Bergey et al. 1925 (Approved Lists 1980)
* '' C. lactis'' Wiertz et al. 2013
* "'' C. lactofermentum''" Gubler et al. 1994

* '' C. jeikliangguodongiiium'' Zhu et al. 2020

* '' C. lipophiloflavum'' Funke et al. 1997

* '' C. lizhenjunii'' Zhou et al. 2021
* '' C. lowii'' Bernard et al. 2016
* '' C. lubricantis'' Kämpfer et al. 2009
* '' C. lujinxingii'' Zhang et al. 2021
* '' C. macginleyi'' Riegel et al. 1995
* '' C. marinum'' Du et al. 2010
* '' C. maris'' Ben-Dov et al. 2009
* '' C. massiliense'' Merhej et al. 2009
* '' C. mastitidis'' Fernandez-Garayzabal et al. 1997
* '' C. matruchotii'' (Mendel 1919) Collins 1983

* '' C. minutissimum'' (ex Sarkany et al. 1962) Collins and Jones 1983

* '' C. mucifaciens'' Funke et al. 1997
* '' C. mustelae'' Funke et al. 2010
* '' C. mycetoides'' (ex Castellani 1942) Collins 1983
* '' C. nasicanis'' Baumgardt et al. 2015

* "'' C. neomassiliense''" Boxberger et al. 2020

* '' C. nuruki'' Shin et al. 2011
* '' C. occultum'' Schaffert et al. 2021
* '' C. oculi'' Bernard et al. 2016

* '' C. otitidis'' (Funke et al. 1994) Baek et al. 2018
* "'' C. pacaense''" Bellali et al. 2019
* "'' C. parakroppenstedtii''" Luo et al. 2022
* "'' C. parvulum''" Nakamura et al. 1983

* '' C. pelargi'' Kämpfer et al. 2015

* '' C. phocae'' Pascual et al. 1998
* "'' C. phoceense''" Cresci et al. 2016
* '' C. pilbarense'' Aravena-Roman et al. 2010
* '' C. pilosum'' Yanagawa and Honda 1978 (Approved Lists 1980)

* '' C. pollutisoli'' Negi et al. 2016
* '' C. propinquum'' Riegel et al. 1994
* "'' C. provencense''" Ndongo et al. 2017
* "''C. provencense''" Lo et al. 2019
* '' C. pseudodiphtheriticum'' Lehmann and Neumann 1896 (Approved Lists 1980)

* "'' C. pseudokroppenstedtii''" Luo et al. 2022
* '' C. pseudopelargi'' Busse et al. 2019
* '' C. pseudotuberculosis'' (Buchanan 1911) Eberson 1918 (Approved Lists 1980)

* '' C. pyruviciproducens'' Tong et al. 2010
* '' C. qintianiae'' Zhou et al. 2021

* '' C. renale'' (Migula 1900) Ernst 1906 (Approved Lists 1980)
* '' C. resistens'' Otsuka et al. 2005
* '' C. riegelii'' Funke et al. 1998
* '' C. rouxii'' Badell et al. 2020

* '' C. sanguinis'' Jaén-Luchoro et al. 2020
* "'' C. segmentosum''" Collins et al. 1998

* "'' C. senegalense''" Ndiaye et al. 2019

* '' C. silvaticum'' Dangel et al. 2020

* '' C. simulans'' Wattiau et al. 2000
* '' C. singulare'' Riegel et al. 1997
* '' C. sphenisci'' Goyache et al. 2003
* '' C. spheniscorum'' Goyache et al. 2003
* '' C. sputi'' Yassin and Siering 2008
* '' C. stationis'' (ZoBell and Upham 1944) Bernard et al. 2010
* '' C. striatum'' (Chester 1901) Eberson 1918 (Approved Lists 1980)
* '' C. suicordis'' Vela et al. 2003
* '' C. sundsvallense'' Collins et al. 1999
* '' C. suranareeae'' Nantapong et al. 2020
* '' C. tapiri'' Baumgardt et al. 2015
* '' C. terpenotabidum'' Takeuchi et al. 1999
* '' C. testudinoris'' Collins et al. 2001

* '' C. thomssenii'' Zimmermann et al. 1998
* '' C. timonense'' Merhej et al. 2009
* '' C. trachiae'' Kämpfer et al. 2015

* '' C. tuberculostearicum'' Feurer et al. 2004

* '' C. tuscaniense'' corrig. Riegel et al. 2006
* "'' C. uberis''" Kittl et al. 2022
* '' C. ulcerans'' (ex Gilbert and Stewart 1927) Riegel et al. 1995
* '' C. ulceribovis'' Yassin 2009

* '' C. urealyticum'' Pitcher et al. 1992
* '' C. ureicelerivorans'' Yassin 2007
* "'' C. urinapleomorphum''" Morand et al. 2017

* '' C. urinipleomorphum'' corrig. Niang et al. 2021
* '' C. urogenitale'' Ballas et al. 2020
* '' C. uropygiale'' Braun et al. 2016
* '' C. uterequi'' Hoyles et al. 2013

* '' C. variabile'' corrig. (Müller 1961) Collins 1987

* '' C. vitaeruminis'' corrig. (Bechdel et al. 1928) Lanéelle et al. 1980

* '' C. wankanglinii'' Zhang et al. 2021
* '' C. xerosis'' (Lehmann and Neumann 1896) Lehmann and Neumann 1899 (Approved Lists 1980)
* '' C. yudongzhengii'' Zhu et al. 2020
* '' C. zhongnanshanii'' Zhang et al. 2021

References

Further reading

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Database of Corynebacterial Transcription Factors and Regulatory Networks
* Rollins, David M. University of Maryland: Pathogentic Microbiology: Corynebacteriu

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Bacteria genera
Corynebacterium
Gram-positive bacteria
Pathogenic bacteria