Corynebacterium is a large genus of bacteria, and while most species live harmlessly on human skin and mucous membranes, a handful can cause serious disease. The most infamous is Corynebacterium diphtheriae, the cause of diphtheria, but a growing number of other species are now recognized as genuine pathogens in hospitals and communities alike. The picture is more varied than the textbook version of “diphtheria and nothing else” suggests, especially as antibiotic-resistant strains gain a foothold in healthcare settings and zoonotic species cross over from household pets.
The Bacterium and Its Unusual Armor
Corynebacteria are club-shaped, Gram-positive rods. What sets the genus apart from many other bacteria is its cell wall, which has a layered architecture more complex than most Gram-positive organisms. The plasma membrane is covered by a peptidoglycan layer, which is covalently linked to a polymer of arabinogalactan. On top of that sits an outer layer of mycolic acids that functions like the outer membrane found in Gram-negative bacteria, and the outermost coat consists of free polysaccharides, glycolipids, and proteins.1PubMed Central. Cell envelope of corynebacteria: structure and influence on pathogenicity This multi-layered envelope helps pathogenic species resist host defenses and contributes to their persistence in wound sites and on medical devices. Recent imaging work has even resolved a patchy outer crystalline layer (S-layer) on some species, which varies depending on growth conditions.2PLoS Biology. Mapping the ultrastructural topology of the corynebacterial cell surface
Diphtheria and the Toxin That Drives It
Diphtheria remains the best-known corynebacterial disease. It is an acute, communicable illness caused by toxin-producing strains of C. diphtheriae. The bacterium typically colonizes the throat, where it multiplies locally and produces a tough pseudomembrane across the tonsils, soft palate, larynx, or nasal passages.3The Journal of Infectious Diseases. The Pathology of Diphtheria The membrane can obstruct the airway, but the real danger comes from the toxin it releases into the bloodstream, which can damage the heart, nerves, and kidneys.
Diphtheria toxin is an extremely potent inhibitor of protein synthesis. The bacterium secretes it as a single polypeptide chain that gets cleaved into two fragments linked by a disulfide bond. Fragment B latches onto a receptor on the target cell surface and ferries fragment A inside, where fragment A shuts down the cell’s protein-making machinery.4PubMed Central. Mechanism of insertion of diphtheria toxin: peptide entry and pore size determinations This is why even a localized throat infection can cause devastating organ damage at distant sites.
One of the stranger twists in microbiology is that the toxin gene does not belong to the bacterium at all. It is carried by a virus that infects the bacterium, a bacteriophage called phage beta. The gene responsible for toxin production, called tox, behaves as a single genetic element on the phage’s genome.5PubMed Central. Genetic analysis of tox+ and tox- bacteriophages of Corynebacterium diphtheriae A strain of C. diphtheriae that has never been infected by a tox-carrying phage is non-toxigenic and cannot cause classical diphtheria. This also means laboratory testing for toxin production is critical when C. diphtheriae is isolated from a patient.
Myocarditis, Nerve Damage, and Other Complications
When diphtheria toxin circulates through the body, the heart and nervous system are particularly vulnerable. Myocarditis, an inflammation of the heart muscle, is the most feared complication and a leading cause of death in severe cases. Nerve damage can cause paralysis of the palate, eye muscles, or limbs weeks after the initial infection, and in extreme cases affects the muscles used for breathing. A Swedish case report documented a patient who developed both myocarditis and severe neurological disease during care for diphtheria and was simultaneously co-infected with tuberculosis.6PubMed Central. Severe diphtheria with neurologic and myocardial involvement in a Swedish patient: a case report
The primary treatment for toxin-mediated diphtheria has barely changed in principle since the 1890s. Equine diphtheria antitoxin, a preparation of antibodies harvested from horses immunized against the toxin, remains the cornerstone of treatment for systemic complications.7PubMed Central. Diphtheria antitoxin treatment: from pioneer to neglected The pioneering work behind this therapy earned Emil von Behring the very first Nobel Prize in Medicine in 1901.8PubMed Central. Remembering Emil von Behring: from Tetanus Treatment to Antibody Cooperation with Phagocytes Antibiotics such as penicillin or erythromycin are given alongside to kill the bacteria and stop toxin production, but antitoxin is what neutralizes toxin already in the bloodstream. Despite being one of the oldest biological medicines in continuous use, antitoxin supply has become precarious in many countries, a problem that has received growing attention.
Cutaneous Diphtheria Is More Common Than Many Realize
Diphtheria is not only a throat disease. Cutaneous diphtheria, where the bacterium infects skin wounds, is actually more common globally than the respiratory form, especially in tropical climates and among displaced populations. A German multi-center study of adolescent refugees found 31 individuals with cutaneous C. diphtheriae infections over about 16 months. Most had exclusively skin-level disease and remained afebrile, though two patients developed systemic symptoms related to diphtheria toxin and four showed systemic inflammation requiring complex management.9PubMed Central. Management and outcome of cutaneous diphtheria in adolescent refugees in Germany, June 2022 – October 2023 Treatment with topical antiseptics and systemic antibiotics, mainly amoxicillin-clavulanate or clindamycin for five to seventeen days, achieved bacterial clearance in nearly all cases.
A French cohort study found that all patients with cutaneous C. diphtheriae presented with painful ulcerations, though the strains in that series were non-toxigenic.10PubMed. Cutaneous infections with Corynebacterium diphtheriae in France: A cohort study This highlights an important point: even strains that lack the toxin gene can still cause chronic, painful skin infections that require antibiotic treatment. Complete antibiotic therapy and up-to-date immunization for both patients and their close contacts are recommended regardless of toxin status.11PubMed Central. Cutaneous Diphtheria: A Case Report
Vaccine Protection and Why It Fades
Widespread vaccination against diphtheria toxin is the main reason the disease has become rare in high-income countries. The vaccine uses an inactivated form of the toxin (toxoid) and is given as part of childhood immunization schedules, typically in combination with tetanus and pertussis vaccines. But immunity wanes over time, and how quickly it fades depends heavily on how many doses a person has received.
A systematic review analyzing data across studies found that after three primary doses, average antibody levels dropped to the threshold considered protective in roughly two and a half years. After four doses, that protective level lasted an estimated ten years, and after five doses it held for about twenty-five years. The annual rate of antibody decline also slowed with more doses: roughly a quarter of the measured antibody concentration per year after three doses, compared to about seven percent per year after five.12PubMed Central. Waning rate of immunity and duration of protective immunity against diphtheria toxoid as a function of age and number of doses This is why booster doses matter. Adults who have not had a tetanus-diphtheria booster in a decade or more may have very little residual protection, and serological surveys in many countries have found that a substantial proportion of older adults have antibody levels below the protective threshold.
Hospital-Acquired Infections From Species Nobody Used to Worry About
For decades, clinical microbiology labs routinely dismissed Corynebacterium species found in patient cultures as contaminants. These bacteria were collectively called “diphtheroids” and treated as background noise from the skin. That attitude has shifted as evidence has accumulated that several non-diphtheriae species can cause genuine, sometimes life-threatening infections, particularly in people with weakened immune systems or indwelling medical devices.13PubMed Central. The genus corynebacterium and other medically relevant coryneform-like bacteria
Corynebacterium jeikeium is one of the more aggressive opportunistic species. It lives on normal skin but can invade the bloodstream in people with cancer, severe neutropenia, or implanted devices. First described in 1976 as a highly resistant bacterium causing severe bloodstream infections in patients with blood cancers, it has since been linked to endocarditis, meningitis, pneumonia, bone infections, and soft-tissue infections.14PubMed Central. Disseminated Corynebacterium jeikeium Infection in Cancer Patients It is considered part of the normal skin flora but is especially found in hospitalized patients and the broader hospital environment.15International Journal of Infectious Diseases. Corynebacterium jeikeium bacteremia in a hemodialyzed patient In pediatric oncology wards, C. jeikeium and related species such as C. amycolatum have been isolated from central venous catheter infections, with bacteremia occurring in neutropenic patients.16The Brazilian Journal of Infectious Diseases. Central venous catheter-related infections caused by Corynebacterium amycolatum and other multiresistant non-diphtherial corynebacteria in paediatric oncology patients
Corynebacterium urealyticum occupies a different niche. This species has a powerful urease enzyme that splits urea into ammonia, making the urine alkaline. The alkaline environment causes minerals to precipitate out and form crusty deposits on the bladder wall, a condition called encrusted cystitis. About twelve percent of healthy people carry the organism on their skin, but it has been isolated from roughly thirty percent of hospitalized patients. Prolonged urinary catheterization is the biggest risk factor, because it can introduce the bacterium into the urinary tract and damage the lining, creating the conditions for encrustation.17Oxford Academic. Encrusted cystitis by Corynebacterium urealyticum: a case report with novel insights into bladder lesions
Antibiotic Resistance in Corynebacterium striatum
Perhaps the most worrying trend in non-diphtheriae corynebacterial infections is the rise of multidrug-resistant Corynebacterium striatum. Once considered an unremarkable skin commensal, C. striatum has emerged as a genuine nosocomial pathogen in intensive care units and long-term care facilities worldwide.
A study from a Tunisian hospital found that nearly all of its C. striatum isolates showed resistance to at least one antibiotic, and about half were multidrug-resistant, meaning they were resistant to agents across three or more antibiotic classes. Some isolates resisted eight or more compounds spanning seven major drug classes, including aminoglycosides, macrolides, fluoroquinolones, and penicillins.18Scientific Reports. Occurrence of Corynebacterium striatum as an emerging antibiotic-resistant nosocomial pathogen in a Tunisian hospital A hospital-wide analysis in Beijing found an even starker picture: over ninety-six percent of the 190 C. striatum isolates tested were multidrug-resistant, with resistance to ciprofloxacin approaching ninety-nine percent. Genomic analysis revealed that two dominant clones had spread throughout the hospital, progressively acquiring new resistance genes.19PubMed Central. Whole-Genome Sequencing Reveals a Prolonged and Persistent Intrahospital Transmission of Corynebacterium striatum, an Emerging Multidrug-Resistant Pathogen
The practical concern is that C. striatum can colonize ventilator circuits, wound sites, and catheters, and when it turns invasive in a debilitated patient, few antibiotics reliably work. Vancomycin and linezolid tend to remain effective, but they are reserve agents with their own toxicities. The rapid accumulation of resistance genes within hospital clones suggests this problem will get worse before it gets better.
Zoonotic Infections From Pets
Corynebacterium ulcerans is a close relative of C. diphtheriae and can carry the same toxin gene. Unlike C. diphtheriae, which is strictly a human pathogen, C. ulcerans circulates in animals and can jump to people. It has been found in dogs, cats, and livestock, and transmission from household pets to their owners has been documented repeatedly.
A Japanese case report described a woman who developed a diphtheria-like illness with airway obstruction. Molecular typing confirmed that the same toxigenic strain was present in both the patient and her domestic cats.20PubMed Central. Transmission of toxigenic Corynebacterium ulcerans infection with airway obstruction from cats to a human The first reported U.S. cases of toxigenic C. ulcerans in humans with concurrent pet colonization surfaced in Utah and Colorado in 2022 and 2023. Investigators found evidence of transmission between humans and their household pets, though which direction it went could not be pinned down. Human-to-human transmission of C. ulcerans has not been documented.21Morbidity and Mortality Weekly Report. Notes from the Field: Toxigenic Corynebacterium ulcerans in Humans and Household Pets — Utah and Colorado, 2022–2023 Companion dogs have also been identified as probable sources for human cases using whole-genome sequencing, though guidelines for managing animal contacts remain inconsistent across different jurisdictions.22PubMed. Zoonotic transmission of diphtheria toxin-producing Corynebacterium ulcerans
Because diphtheria vaccination protects against the toxin rather than the bacterium itself, vaccinated people may still become colonized with C. ulcerans but are protected from the worst toxin-mediated complications. The risk is highest for unvaccinated or under-vaccinated individuals living in close contact with animals that carry the organism.
How Labs Tell a Pathogen From a Contaminant
One of the persistent challenges with corynebacterial infections is knowing when to take a positive culture seriously. Since many Corynebacterium species live on normal skin, they frequently show up in blood cultures, wound swabs, and catheter tips simply because the sample touched skin on the way to the lab. The historical tendency to dismiss all corynebacteria as contaminants means genuine infections can go untreated, while the opposite error, treating every positive culture with antibiotics, fuels resistance.
When C. diphtheriae or C. ulcerans is suspected, determining whether the strain produces toxin is the key clinical question. The Elek test, a century-old immunoprecipitation method, remains widely used. Recent optimization work has shown the test can reliably detect toxin production using colonies taken directly from primary tellurite agar plates, speeding up the process.23PubMed Central. Detection of diphtheria toxin production by toxigenic corynebacteria using an optimized Elek test Molecular methods have also advanced: a multiplex PCR assay can now simultaneously identify the species and determine whether it carries toxin genes, including some non-toxigenic tox-bearing strains that older PCR panels missed.24Journal of Microbiological Methods. New approach for the identification of potentially toxigenic Corynebacterium sp. using a multiplex PCR assay
For non-diphtheriae species in hospital settings, the clinical context matters more than the species name. A single blood-culture bottle positive for C. striatum in a healthy outpatient is almost certainly contamination. The same organism growing from multiple blood cultures in a patient on a ventilator with a central line and a fever is a different story entirely. Clinicians increasingly rely on clinical criteria, repeat cultures, and the patient’s immune status to make the call.
Caseous Lymphadenitis in Livestock
Corynebacterium pseudotuberculosis is the one member of the genus that has its greatest impact outside human medicine. It causes caseous lymphadenitis, a chronic disease of goats and sheep characterized by abscesses in lymph nodes and internal organs. The disease causes significant economic losses in small-ruminant farming worldwide through reduced wool and milk production, carcass condemnation, and culling of infected animals.25PubMed. Evaluation of the humoral and cellular immune response to different antigens of Corynebacterium pseudotuberculosis in Canindé goats and their potential protection against caseous lymphadenitis Experimental studies have shown the bacterium can spread to the reproductive organs and inguinal lymph nodes of goats after skin inoculation, reaching those tissues within 60 to 90 days.26PubMed Central. Isolation and detection of Corynebacterium pseudotuberculosis in the reproductive organs and associated lymph nodes of non-pregnant does experimentally inoculated through intradermal route in chronic form Human infections with C. pseudotuberculosis are rare but not unheard of, typically occurring in people who handle infected animals or consume unpasteurized dairy products.
When Corynebacterium Works for Us
Not every member of the genus is a villain. Corynebacterium glutamicum, a soil bacterium, is one of the most important microorganisms in industrial biotechnology. It has been used since the late 1950s for the large-scale production of amino acids, particularly L-glutamate (the basis of MSG) and L-lysine (a major feed additive). Modern metabolic engineering has expanded its repertoire to include a range of bulk chemicals and specialty compounds used in food, feed, and health products.27PubMed Central. Advances in metabolic engineering of Corynebacterium glutamicum to produce high-value active ingredients for food, feed, human health, and well-being The global amino acid market, worth tens of billions of dollars annually, depends heavily on this single species. Researchers studying pathogenic corynebacteria have benefited enormously from the detailed genetic and biochemical knowledge built up in C. glutamicum, since the cell-wall architecture is similar across the genus. Findings about the mycolate membrane and surface proteins in the industrial strain have informed understanding of how pathogenic relatives interact with host tissues and resist antibiotics.