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Corynebacterium

Corynebacterium is a of Gram-positive, rod-shaped belonging to the phylum Actinobacteria, characterized by their pleomorphic, often club-shaped morphology, non-motile nature, and catalase-positive activity. These typically exhibit high G+C content in their DNA (ranging from 46% to 74%) and are either aerobic or facultatively , with approximately 170 validated as of 2025. Commonly found in diverse environments such as , , and as commensals on and mucous membranes, certain are significant pathogens or organisms. Medically, Corynebacterium species are notable for their role in infections, with C. diphtheriae being the primary cause of , a severe respiratory or cutaneous disease resulting from the production of a potent that inhibits protein synthesis in host cells. Other species, such as C. ulcerans and C. pseudotuberculosis, can cause zoonotic infections including diphtheria-like illnesses and caseous lymphadenitis in animals, respectively, while opportunistic pathogens like C. jeikeium and C. striatum are associated with nosocomial infections such as , bacteremia, and infections, particularly in immunocompromised individuals. Transmission often occurs via respiratory droplets, direct contact, or environmental fomites, and while is preventable through , emerging multidrug-resistant strains pose challenges in treatment. Beyond pathology, the genus holds industrial value, exemplified by C. glutamicum, a non-pathogenic species widely used in for the large-scale production of like L-glutamate and L-lysine, which are essential in food additives and . Taxonomically, species identification relies on methods such as 16S rRNA gene sequencing and rpoB gene analysis, reflecting the genus's phylogenetic diversity within the family Corynebacteriaceae. Overall, Corynebacterium exemplifies a versatile bacterial group bridging environmental adaptation, human health impacts, and biotechnological applications.

Taxonomy

Etymology and History

The genus name Corynebacterium derives from the Greek "korynē" (κορύνη), meaning , and "baktērion" (βακτήριον), meaning small or , alluding to the distinctive club-shaped or irregularly swollen observed in these . This nomenclature was formally proposed by Karl Bernhard Lehmann and Rudolf Otto in their 1896 bacteriological atlas, where they established the to encompass nonmotile, parasitic rods exhibiting this characteristic form, including the . The historical recognition of Corynebacterium began with the identification of C. diphtheriae as the etiological agent of , a major childhood disease in the 19th century. In 1883, Edwin Klebs first observed the bacterium in diphtheritic pseudomembranes, but it was Friedrich Loeffler who, in 1884, successfully isolated it in pure culture from infected tissues and fulfilled by reproducing the disease in animals, thereby linking the organism directly to pathogenesis. This isolation paved the way for the genus's formal establishment, as Lehmann and grouped C. diphtheriae—originally termed "Bacillus diphtheriae" by Loeffler—with similar club-shaped rods to differentiate them taxonomically. A pivotal advancement came in 1888 when Émile Roux and at the demonstrated that C. diphtheriae produced a soluble responsible for the systemic effects of , beyond local infection; they achieved this by injecting cell-free filtrates of bacterial cultures into pigs, which induced characteristic symptoms and death. This discovery not only elucidated the toxigenic mechanism but also spurred immunological research, including development. In the late , early classifications often lumped these organisms with branching actinomycetes like due to shared Gram-positive staining and rod-like forms, but Lehmann and Neumann's work shifted them to a distinct based on non-branching, pleomorphic and metachromatic granule staining properties. This separation reflected growing appreciation for morphological nuances in .

Classification and Phylogeny

Corynebacterium belongs to the Actinobacteria, class Actinomycetia, order Corynebacteriales, and family Corynebacteriaceae. This placement is supported by genome-based taxonomic analyses that delineate boundaries within the using average nucleotide identity and digital DNA-DNA hybridization values. The encompasses 168 species (as of November 2025), distinguished by their high G+C content in DNA, a characteristic shared across the Actinobacteria. Phylogenetically, Corynebacterium forms part of the CMN clade, which includes the genera Mycobacterium and Nocardia, based on 16S rRNA gene sequence analyses that reveal a monophyletic grouping within the high G+C . Close relationships extend to Arthrobacter, with some species historically reclassified between the genera due to shared biochemical and 16S rRNA similarities. These affiliations are further corroborated by conserved signature indels and signature proteins unique to Actinobacteria, providing molecular markers for the clade that encompass Corynebacterium and its relatives. Within the genus, species are divided into phylogenetic clusters derived from small-subunit rRNA sequence analyses. Cluster I comprises human and animal pathogens such as C. diphtheriae, C. ulcerans, and C. pseudotuberculosis, forming a robust monophyletic unit. Cluster II includes C. jeikeium, while Clusters III and IV encompass species like C. glutamicum and C. amycolatum, often associated with environmental niches such as . Species delineation has advanced with multi-locus typing (MLST), which sequences housekeeping genes to identify sequence types and detect recombination, as demonstrated in C. diphtheriae where it reveals distinct lineages. Whole-genome phylogenomics, accounting for , refines these relationships by constructing trees from core genomes, enhancing resolution for closely related taxa within Corynebacteriales.

Genomics

Genome Organization

The genomes of Corynebacterium species typically consist of a single circular with sizes ranging from 2.3 to 3.5 . These chromosomes exhibit a high G+C content, varying between 46 and 74 %, which contributes to the genetic stability and codon usage biases observed in this . For instance, the genome of C. glutamicum ATCC 13032 measures 3.3 with a G+C content of 53.8 %, while C. diphtheriae NCTC 13129 has a 2.5 at approximately 53.5 % G+C. Conserved genomic regions in Corynebacterium include the dapA-dapB , which encodes enzymes essential for diaminopimelate (DAP) synthesis and thus biosynthesis in the . The dapA codes for dihydrodipicolinate , which catalyzes the of aspartate-semialdehyde and pyruvate to form a key intermediate, while dapB encodes dihydrodipicolinate reductase, reducing this intermediate to tetrahydrodipicolinate. This is transcriptionally regulated and plays a in both production and integrity across like C. glutamicum. In pathogenic such as C. diphtheriae, additional conserved elements include toxin genes like tox, which encodes the and is integrated into the via lysogenic phage. Many Corynebacterium species harbor plasmids that confer traits such as or enhanced metabolic capabilities. For example, plasmids in the pCG1 family, native to C. glutamicum, are small (around 5-7 kb), cryptic elements with rolling-circle replication mechanisms that maintain low to moderate copy numbers. These plasmids, such as pCG1 itself, lack inherent resistance genes but serve as backbones for engineering metabolic pathways, including overproduction, by stably replicating without imposing significant metabolic burden. In contrast, other plasmids like pTET3 in C. glutamicum isolates encode , aiding survival in selective environments. CRISPR-Cas systems are present in multiple Corynebacterium species, providing adaptive immunity against bacteriophage infections through targeted DNA cleavage. In C. diphtheriae, type I-E and type II CRISPR-Cas variants have been identified, featuring cas gene clusters (e.g., cas1, cas2, cas9) adjacent to CRISPR arrays with 28-40 bp spacers derived from past phage encounters. These systems enable sequence-specific defense by incorporating new spacers during phage exposure, with the type II system in some strains showing novel configurations lacking certain cas genes but retaining interference functionality. Similar CRISPR arrays occur in non-pathogenic species like C. glutamicum, underscoring their role in phage resistance across the genus.

Comparative Genomics

Comparative genomic analyses have identified molecular markers, including conserved signature indels (CSIs) and conserved signature proteins (CSPs), that distinguish the Corynebacterium from other Actinobacteria. For the Corynebacteriales (encompassing Corynebacterium), three CSIs have been described: a 2-amino-acid insertion in the ABC-F family ATP-binding protein (Uup), a 1-amino-acid insertion in the chromosome partitioning protein ParB, and a 1-amino-acid deletion in alpha-ketoglutarate decarboxylase (KGD). Additionally, two CSPs (accession numbers NP_301197.1 and NP_301204.1) are uniquely found in members of this , providing robust phylogenetic markers for taxonomic circumscription. These signatures are absent in other Actinobacteria clades, supporting the of Corynebacteriales and highlighting evolutionary divergences within the . Pan-genome studies of Corynebacterium reveal an open and expansive repertoire, with a total of 114,775 identified across 140 strains, comprising 175 core present in 99–100% of genomes and 131 conserved in all strains. Core essential for synthesis, such as accD4, pks13, fadD32, and cmrA, are highly conserved, underscoring their fundamental role in cell envelope integrity and distinguishing Corynebacterineae from other . In contrast, the majority of (112,680 cloud present in ≤15% of genomes and 1,846 shell in 15–95%) represent accessory elements that facilitate niche , including those for environmental sensing, transport, and host interaction, enabling species-specific colonization of diverse habitats like , , and animal hosts. Recent genomic studies from 2020–2025 have elucidated microevolutionary dynamics in Corynebacterium, particularly in zoonotic species. A comprehensive of 582 C. ulcerans isolates from humans, pets, and across global locations identified 42 clonal groups and 17 sublineages using a core multilocus sequence typing scheme with 1,628 loci, revealing two dominant sublineages (SL325 and SL331) that account for over 70% of toxigenic strains. This work demonstrated frequent host jumps, with cryptic clusters indicating multi-host transmission involving companion animals and , but limited direct human- links, highlighting adaptive driven by ecological pressures. Horizontal gene transfer (HGT) plays a pivotal role in Corynebacterium evolution, notably through prophage integration that mobilizes . In C. ulcerans, the tox encoding is often carried on distinct , such as ΦCULC0102-I in strain 0102, which integrates into the tRNA^Arg and exhibits low (<18%) to in C. diphtheriae NCTC 13129, indicating independent acquisition events. Comparative analyses across show -mediated cross- of families, with five families identified in C. ulcerans, where variability in tox presence (e.g., 68.7% toxigenic in clonal group CG583) reflects ongoing HGT and contributes to pathogenicity emergence.

Morphology and Physiology

Cellular Morphology

Corynebacterium species are Gram-positive, non-motile, non-spore-forming rods characterized by a club-shaped appearance, with cells typically measuring 0.3–1.0 μm in diameter and 1.0–8.0 μm in length. These often exhibit irregular staining due to variations in thickness, appearing as straight, slightly curved, or swollen at one end. Under light microscopy, they frequently arrange in palisades, forming V- or L-shaped configurations, or cluster in angular patterns resembling . Cells of Corynebacterium display pleomorphism, manifesting as coccal, rod-like, or elongated filamentous forms, particularly under environmental stress such as limitation or exposure. This variability in shape and size contributes to their adaptability in diverse habitats. A distinctive feature is the presence of metachromatic granules, also known as volutin or Babes-Ernst bodies, which are intracellular deposits of that serve as storage. These granules, located at the poles, stain prominently with Albert's or Neisser's methods, appearing as dark blue or black against a lighter bacterial background, aiding in microscopic identification. Corynebacterium species are catalase-positive, facilitating the breakdown of hydrogen peroxide, while oxidase activity is variable across strains, with most testing negative. They are generally aerobic or facultatively anaerobic, supporting growth in oxygen-variable conditions.

Cell Wall Composition

The cell wall of Corynebacterium species forms a complex, multilayered envelope that distinguishes members of the Corynebacterineae suborder from other Gram-positive bacteria. The innermost component is peptidoglycan, classified as A1γ type, consisting of alternating β-1,4-linked N-acetylglucosamine and N-acetylmuramic acid residues cross-linked primarily through meso-diaminopimelic acid (meso-DAP) bridges between D-alanine and either glutamate or another DAP residue. This structure provides mechanical strength and shape maintenance to the rod-shaped cells. Covalently linked to the via phosphodiester bonds to muramic acid is , a highly branched heteropolysaccharide primarily composed of D-arabinofuranose and D-galactofuranose units, with species-specific inclusions such as in C. diphtheriae or glucose in C. amycolatum. The non-reducing terminal arabinan domains of are esterified with mycolic acids, which are α-branched, β-hydroxy fatty acids termed corynomycolates, typically containing 22–36 carbon atoms in total chain length. These mycolic acids, shorter than the 60–90 carbon counterparts in mycobacteria, form an outer pseudo-membrane layer that enhances hydrophobicity. The integrated mycolyl-arabinogalactan-peptidoglycan (mAGP) complex serves as the core scaffold of the , conferring low permeability to hydrophobic and hydrophilic molecules alike, akin to the outer membrane of . Non-covalently associated with the mAGP are lipoglycans, including lipomannan () and lipoarabinomannan (), which are glycosylated phosphatidyl-myo-inositol anchors with mannosylated or arabinomannosylated chains; these modulate innate immune recognition by interacting with host receptors, thereby contributing to immune evasion in pathogenic contexts. Species-specific variations in lipoglycan composition, such as predominance of LM in C. glutamicum versus LAM in C. xerosis, further influence host interactions. Mycolic acid profiles exhibit interspecies variation within the genus, with commensal species generally featuring shorter or more polar corynomycolates compared to the longer, less polar chains in pathogens like C. diphtheriae, impacting envelope integrity and potential.

Growth Requirements and Culture

Corynebacterium exhibit optimal at temperatures ranging from 30°C to 37°C, with many strains, such as those in medical contexts, thriving at 37°C under aerobic or microaerophilic conditions. The preferred range is 7.0 to 7.5, supporting robust in neutral to slightly alkaline environments. Oxygen requirements vary, but most are facultative aerobes capable of growth in ambient air, though some benefit from 5% CO₂ supplementation for enhanced recovery. Many Corynebacterium species display biotin auxotrophy, necessitating supplementation for growth; for instance, Corynebacterium glutamicum requires approximately 1 μg/L of in minimal media to achieve full development. Lipophilic strains, such as certain diphtheroids, further demand lipid additives like 0.1–1% Tween 80 to prevent poor or absent growth on standard media. In cultivation, Corynebacterium grows slowly, typically requiring 24 to 72 hours to form visible colonies, which appear as small (less than 1 mm), gray-white, dry, and non-hemolytic on blood agar. On Loeffler's serum medium, colonies develop as minute, cream-colored formations with slightly raised centers after 24–48 hours at 35–37°C, facilitating observation of characteristic metachromatic granules. Selective media enhance isolation; cysteine-tellurite agar or Tinsdale agar yields black colonies due to tellurite reduction, particularly useful for identifying toxin-producing strains like . Biochemical confirmation during culture includes variable nitrate reduction across species and urease positivity in select members, such as , aiding differentiation.

Ecology and Habitat

Natural Environments

Corynebacterium species are ubiquitous in various non-host natural environments, including , freshwater systems, , and surfaces, where they contribute to ecological processes such as the of . In , these facilitate the breakdown of complex materials, including livestock remains, thereby reducing environmental and aiding through processes like turnover. For instance, Corynebacterium glutamicum has been shown to accelerate the of buried animal carcasses, mitigating the release of harmful byproducts into the . In freshwater ecosystems, Corynebacterium isolates are detected in tropical rivers and lakes, often associated with nutrient-rich sediments, while in systems, species like Corynebacterium defluvii have been isolated from . On surfaces, Corynebacterium species colonize foliage and , contributing to the degradation of plant-derived organics without causing widespread in natural settings. These are frequently isolated from products and contaminated sources, highlighting their adaptability to nutrient-variable niches. In cheese production, particularly smear-ripened varieties, Corynebacterium casei and Corynebacterium variabile dominate surface microflora, where they drive by metabolizing and proteins to develop and compounds. Isolation from bulk tank and artisanal cheeses underscores their environmental ingress via contaminated or feed. In contaminated waters, Corynebacterium strains are recovered from phenol- and arsenic-polluted sites, where they exhibit potential by detoxifying and organic pollutants through efflux systems and enzymatic degradation. Corynebacterium demonstrate key environmental adaptations, including formation on abiotic surfaces and to osmotic , which enhance their persistence in fluctuating habitats. production, a communal strategy involving secretion, protects cells from , nutrient scarcity, and shear forces in and environments, as observed in natural polymicrobial communities. Osmotic is mediated by osmoregulatory mechanisms, such as betaine uptake and compatible solute accumulation, allowing efficient to shifts in and interfaces. Their high G+C content genomes further support survival across diverse osmotic and nutritional conditions. Recent findings from 2020 to 2025 have expanded understanding of Corynebacterium distribution, including presence in preen glands and soils linked to novel . Studies on uropygial microbiomes in birds confirm Corynebacterium as recurring components, potentially influencing maintenance through volatile compound production. In ecosystems, the description of Corynebacterium silvaticum, a new isolated from forest animals such as and , highlights potential zoonotic interfaces.

Host Associations

Corynebacterium species are prominent members of the normal , particularly on moist sites such as the and , where they contribute to the resident community alongside staphylococci. In the nasopharynx, these bacteria transiently colonize the mucosal surfaces, serving as commensals that interact with other respiratory microbes. Additionally, Corynebacterium is detected in the urogenital tract, including the urinary and vaginal regions, often as an occasional colonizer when dominant populations are reduced. Densities of Corynebacterium on can reach up to 10^6 CFU/cm² in these areas, with variations influenced by hygiene practices and environmental factors. In animal hosts, Corynebacterium species similarly occupy skin and mucosal niches, such as the of , where they form part of the normal ocular surface in healthy individuals. For instance, species like Corynebacterium stationis and Corynebacterium variabile are present at higher relative abundances in unaffected bovine eyes compared to those with infections. Dairy-associated strains, including those isolated from and environments, highlight their adaptation to veterinary settings without necessarily causing disease. As commensals, Corynebacterium plays a modulatory role in host , particularly in the nasopharynx, where it influences interactions with pathogens like . A 2025 study demonstrated that respiratory Corynebacterium strains, such as Corynebacterium propinquum and Corynebacterium pseudodiphtheriticum, reduce pneumococcal burden in the lungs by dampening excessive inflammatory responses, including lowered production of pro-inflammatory cytokines like TNF and IL-12. This protective effect underscores their contribution to stability and respiratory health in both human and animal hosts.

Pathogenicity

Diphtheria and Toxin Production

Corynebacterium diphtheriae is the primary etiologic agent of diphtheria, an acute bacterial infection primarily affecting the upper respiratory tract. The species is classified into biovars based on biochemical properties and colony morphology, including gravis, mitis, and belfanti, all of which can produce the diphtheria toxin responsible for the disease's severe manifestations. The gravis biovar is associated with more severe disease presentations, while mitis tends to cause milder forms, though toxin production capability varies across strains rather than strictly by biovar. The , an , is encoded by the tox gene carried on the beta-corynephage, a temperate that lysogenizes C. diphtheriae upon , converting non-toxigenic strains to toxigenic ones. This AB-type consists of an A subunit that catalyzes the of elongation factor 2 (EF-2) in eukaryotic cells, halting protein synthesis and leading to . The B subunit facilitates and translocation of the A subunit into the , where it exerts its cytotoxic effects. expression is regulated by iron availability, with low iron levels promoting transcription via the diphtheria repressor (DtxR) protein. Clinically, diphtheria manifests as pharyngitis with formation of a characteristic grayish-white pseudomembrane on the tonsils, , or , composed of , necrotic , , and inflammatory cells, which can lead to airway obstruction. Systemic toxin dissemination causes complications such as , which occurs in up to 20% of cases and accounts for much of the mortality, and peripheral neuropathy affecting cranial and peripheral nerves, leading to . The is typically 2 to 5 days, with transmission occurring via respiratory droplets from infected individuals or close contacts. Epidemiologically, diphtheria incidence has declined globally since the introduction of diphtheria-tetanus-pertussis (DTP) in the 1940s, which contain inactivated diphtheria to induce protective antibodies against the . The demonstrates efficacy exceeding 95% in eliciting protective levels after a primary series of three doses plus boosters. However, resurgences occur in unvaccinated or undervaccinated populations, particularly in regions with low immunization coverage, as seen in outbreaks among adults with waning immunity or in areas with disrupted programs. Diagnosis relies on clinical suspicion confirmed by laboratory tests, including culture of the organism from throat swabs or lesions followed by the Elek immunoprecipitation test to detect toxin production. (PCR) assays targeting the tox provide rapid identification of toxigenic strains, though they require correlation with toxin assays for confirmation. Treatment involves immediate administration of diphtheria to neutralize circulating , sourced from serum and distributed through authorities, combined with antibiotics such as erythromycin or penicillin to eradicate the and halt production. Supportive care, including , is essential, and vaccination status should be updated post-recovery. The cell wall components of C. diphtheriae contribute to initial adherence to host mucosal surfaces, facilitating infection.

Opportunistic Infections

Non-toxigenic species of Corynebacterium are frequent commensals on and mucosal surfaces but can cause opportunistic infections in vulnerable individuals, particularly those with compromised immune systems or invasive medical procedures. These infections are typically nosocomial or healthcare-associated, arising from endogenous translocation during breaches in host defenses. Among the most clinically significant species, C. jeikeium is notorious for causing and bacteremia, especially in immunocompromised patients such as those undergoing or with indwelling catheters. It often leads to prosthetic valve and septicemia, with cases reported in patients and those with malignancies. Similarly, C. striatum is associated with , catheter-related , and prosthetic joint infections, frequently in settings. C. pseudodiphtheriticum, another key , primarily causes native valve , though it can also involve urinary tract and wound sites. Key risk factors include the presence of indwelling medical devices like central venous catheters and prosthetic materials, which facilitate bacterial adhesion and formation; underlying conditions such as , chemotherapy-induced , and hematologic malignancies further predispose individuals by impairing immune clearance. Multidrug resistance complicates management, particularly in C. jeikeium, where efflux pumps contribute to resistance against beta-lactams, aminoglycosides, and , often necessitating glycopeptide therapy like . C. striatum strains similarly exhibit resistance via genes such as ermX for and tetA/B for tetracyclines. Clinical presentations vary by site but commonly involve skin and soft tissue infections (approximately 7-30% of cases in surveyed cohorts), catheter-related (up to 28%), and respiratory tract involvement like . without a defined focus account for a substantial portion (around 25-42%), often presenting with fever and in at-risk patients. Mortality rates in severe cases, such as bacteremia due to C. striatum or C. jeikeium, range from 10-40%, influenced by underlying comorbidities and delayed . Recent studies from 2023-2025 highlight C. striatum as an emerging hospital-acquired with demonstrated intracellular potential in human airway epithelial cells, enabling persistence and virulence in immunocompromised hosts like oncology patients. These findings underscore its role in invasive infections beyond surface colonization, with genomic analyses revealing adaptive mechanisms for nosocomial spread.

Emerging Pathogens and Zoonoses

Recent outbreaks of have been reported in European migrant reception centers from 2022 to 2025, primarily involving the sequence type ST574 strain. Between 2023 and 2025, the / (EU/EEA) documented 82 cases caused by this strain, with 25 resulting in severe outcomes such as systemic complications. These incidents began in the summer of 2022 among migrants in overcrowded facilities across multiple countries, including , Czechia, , , , and , highlighting vulnerabilities in coverage and living conditions. Zoonotic transmission of Corynebacterium ulcerans has emerged as a significant concern, with cases linked to pets and causing cutaneous -like infections. In 2023, a confirmed instance involved zoonotic spread from domestic dogs to humans, resulting in skin lesions consistent with toxigenic cutaneous . Similarly, infections traced to have been documented, where occupational exposure led to -like or wound infections in humans. From 2015 to 2023, five confirmed zoonotic cases in , , linked to companion animals such as dogs and cats, with toxigenic strains isolated from both animal carriers and affected individuals, underscore the pathogen's in pets. Human infections by the novel zoonotic species Corynebacterium silvaticum were reported in in 2025, manifesting as axillary lymphadenitis and abscess formation. Two cases involved likely transmission from wild or animal sources, with one patient developing localized swelling and the other an abscess requiring drainage; both isolates were confirmed via whole-genome sequencing. These incidents represent the first documented human infections by C. silvaticum, previously known only from forest animals, indicating potential spillover risks in endemic areas. Beyond diphtheriae-related threats, non-toxigenic species like Corynebacterium pseudodiphtheriticum have gained recognition in community-acquired infections from 2020 to 2025. This organism has been increasingly identified as a cause of respiratory and infections in outpatient settings, often in immunocompetent individuals, with cases involving or reported in observational studies. Additionally, 2025 research has elucidated its role in modulating respiratory pathogens, such as , by altering inflammatory responses and accelerating pathogen clearance in the lungs. In murine models and microbiota analyses, Corynebacterium species, including C. pseudodiphtheriticum, demonstrated protective effects against pneumococcal colonization through competitive exclusion and immune modulation. Genomic analyses from 2020 to 2025 reveal prophage evolution as a key driver enabling toxin production in novel hosts among Corynebacterium species. In C. ulcerans, microevolutionary changes in prophages carrying the tox gene have facilitated adaptation across diverse animal and human reservoirs, with 582 isolates showing recombination events that enhance transmissibility. For C. diphtheriae, prophage integration and mutation in the tox locus have been linked to outbreak strains like ST574, allowing toxin expression in non-traditional human populations. These prophage dynamics, observed in clinical isolates from India and Europe, underscore how lysogenic conversion promotes zoonotic potential and epidemic spread.

Industrial and Biotechnological Applications

Amino Acid Production

Corynebacterium glutamicum has been the primary industrial workhorse for production since its isolation in 1957 by researchers screening for L-glutamic acid producers from samples. The bacterium enables large-scale submerged fermentation of L-glutamic acid, used mainly as (MSG) in food seasoning, with global production reaching approximately 3.6 million metric tons annually as of 2024. Similarly, L-lysine production for supplementation has scaled to over 3.6 million metric tons per year, driven by demand in to balance cereal-based diets. These volumes underscore C. glutamicum's dominance in the sector, contributing to a global market valued at more than USD 29 billion in 2024. Biosynthetic engineering of C. glutamicum targets key pathways to enhance yields. For L-lysine, derived from the aspartate family via the diaminopimelate route, overexpression of dapA (encoding dihydrodipicolinate ) and dapB (encoding dihydrodipicolinate reductase) increases flux through early pathway steps, reducing bottlenecks and boosting by up to 50% in engineered strains. For L-glutamic acid, from the TCA cycle intermediate 2-oxoglutarate, deregulation of activity—achieved through mutations or reduced expression—redirects carbon from the full TCA cycle toward 2-oxoglutarate accumulation, facilitating higher glutamate export under biotin-limited or surfactant-supplemented conditions. These modifications, combined with feedback-resistant variants of aspartate kinase for lysine or for glutamate, have been central to strain optimization since the 1960s. Industrial processes rely on fed-batch submerged fermentation in glucose-based media supplemented with ammonium sulfate as the nitrogen source, maintaining pH around 7 and temperatures of 30–34°C for 40–60 hours. Optimized strains achieve titers exceeding 100 g/L for both L-glutamic acid and L-lysine, with yields of 0.4–0.5 g/g glucose, supported by continuous feeding to minimize by-product formation. The organism's (GRAS) status by the FDA, due to its non-pathogenic nature and absence of endotoxins or phage issues, ensures suitability for and feed applications without posing risks.

Advanced Bioproducts and Engineering

Recent advancements in have expanded the biotechnological potential of Corynebacterium glutamicum beyond traditional production, leveraging its robust physiology as a base for synthesizing high-value aromatics from renewable feedstocks. For instance, engineered strains have achieved titers exceeding 50 g/L of cis,cis-muconic acid, a key precursor for bioplastics and adhesives, through pathway optimization from lignin-derived p-hydroxycinnamates such as p-coumarate. This process involves deregulating flux through the β-ketoadipate pathway and enhancing availability, enabling efficient conversion with yields up to 0.8 g/g substrate. Synthetic biology tools, including CRISPR-based editing, have further diversified product portfolios by enabling precise genomic modifications for pseudoaromatic dicarboxylic acids. A 2024 study demonstrated the production of five such compounds—2-pyrone-4,6-dicarboxylic acid, pyridine-2,6-dicarboxylic acid, pyridine-2,5-dicarboxylic acid, pyridine-3,5-dicarboxylic acid, and dipicolinic acid—in engineered C. glutamicum strains, with titers reaching 15-25 g/L from glucose, highlighting applications in sustainable synthesis. Complementing these efforts, liquid-liquid (LLPS) has been harnessed to create membraneless organelles for pathway compartmentalization, boosting proximity and channeling; in 2025, this approach enhanced indigoidine by 3-fold and yields in C. glutamicum. Beyond aromatics, C. glutamicum serves as a platform for , industrial enzymes such as , and monomers including muconate derivatives, with engineering strategies improving overall process . Exporter , particularly overexpression of systems like BrnFE, has significantly boosted extracellular product accumulation and cellular tolerance, increasing productivity by 20-50% across various bioproducts as reviewed in 2025. These innovations underscore C. glutamicum's role in sustainable , earning it recognition as the "Microbe of the Year 2025" by the German Association of General and Applied (VAAM) for its contributions to green chemical manufacturing.

Species Diversity

Validly Published Species

The genus Corynebacterium encompasses 168 validly published species as recognized by the List of Prokaryotic names with Standing in Nomenclature (LPSN) as of November 2025. The is Corynebacterium diphtheriae (Lehmann and Neumann 1896), which defines the and is notable for its role in disease. These species exhibit diverse ecological niches, with approximately 50 associated with human hosts as pathogens or commensals, while the remainder are primarily environmental isolates from sources such as , water, and animal reservoirs. Among the validly published species, key pathogenic representatives include C. diphtheriae, C. ulcerans, and C. pseudotuberculosis, which share the ability to produce and cause zoonotic infections ranging from respiratory diphtheria-like illnesses to abscesses and lymphadenitis in humans and animals. Commensal species, such as C. accolens and C. amycolatum, are typical constituents of the and upper microbiota, occasionally acting as opportunistic pathogens in immunocompromised individuals. In biotechnological contexts, C. glutamicum stands out as an industrial workhorse, engineered for large-scale production of like L-glutamate and L-lysine. Identification of Corynebacterium species relies on phenotypic traits assessed via systems like API Coryne, which generates biocode profiles based on fermentation, enzymatic reactions, and other biochemical tests. For instance, the lipophilic C. jeikeium, often implicated in nosocomial bacteremia and associated with multidrug resistance, characteristically produces an API Coryne biocode of 2100104. These diagnostic tools, combined with 16S rRNA sequencing for confirmation, facilitate accurate classification within the 's phylogenetic clusters, though environmental species may require additional genomic analysis for precise delineation.

Recently Described Species

In recent years, several new species within the genus Corynebacterium have been validated or proposed, expanding the known diversity of this , which now encompasses 168 recognized . These discoveries, primarily from 2020 to 2025, highlight the bacterium's presence in clinical samples, , and zoonotic reservoirs, often identified through advanced genomic sequencing and polyphasic taxonomy. Corynebacterium incognitum was described in 2021 from a human clinical sample isolated in , , representing a novel member of the with a complete sequence revealing unique phylogenetic placement based on 16S rRNA and core genome analyses. This exhibits typical corynebacterial but shows distinct genomic features, including a of approximately 2.3 , distinguishing it from closely related taxa like C. diphtheriae. Its isolation from a clinical context underscores the potential for undescribed Corynebacterium in human infections, though its pathogenicity remains under investigation. In 2025, Corynebacterium mayonis was formally proposed as a novel isolated from a human blood culture at the , with the type strain BD556^T demonstrating low similarity to existing species via average identity (ANI < 95%) and digital DNA-DNA hybridization (dDDH < 70%). This Gram-positive, non-spore-forming grows optimally at 37°C and is characterized by its ability to ferment glucose and reduce nitrate, features confirmed through phenotypic and chemotaxonomic studies. The discovery emphasizes the role of routine clinical in uncovering new opportunistic pathogens within the Corynebacterium genus. Corynebacterium silvaticum, validated in 2020, originates from caseous lymph node abscesses in and across European forests, marking it as a zoonotic with unique 16S rRNA sequences (99.2-99.6% similarity to C. ulcerans) and a distinct rpoB . By 2025, infections were reported, including axillary lymphadenitis and abscesses in , suggesting emerging zoonotic potential facilitated by close wildlife-human contact; the produces cytotoxic effects on epithelial cells, potentially contributing to damage. Its , around 2.4 Mb, encodes virulence factors analogous to those in diphtheria-related corynebacteria. The reclassification and genomic characterization of Corynebacterium belfantii in 2025, originally proposed in 2018 from the former C. diphtheriae biovar belfanti, confirmed its status as a distinct through complete genome assemblies of representative isolates, showing values below 96% to C. diphtheriae. This non-toxigenic , isolated from pseudomembranes, carries the tox gene locus but lacks production; its 2.5 Mb highlights adaptations for mucosal colonization. Recent studies have expanded the diphtheriae complex to include such with potential for toxin acquisition via lysogeny. A 2025 study on identified two provisional new , including Corynebacterium axilliensis, as commensals enriched via selective and long-read sequencing of 215 isolates from healthy individuals. These skin-associated corynebacteria, with genomes spanning 2.4-2.6 Mb, exhibit high intraspecies diversity and low (<95%) to known taxa, contributing to the underappreciated role of Corynebacterium in cutaneous ecosystems without evident pathogenicity. Such findings from metagenomic and culturomics approaches reveal ongoing expansions in the genus's commensal repertoire.