Corynebacterium are aerobic or facultative Gram-positive rods that tend to form clubs or palisades. They include pathogenic species like C. diphtheriae, which causes diphtheria by producing a toxin that inhibits protein synthesis. Diphtheria presents as a pseudomembrane in the throat and can lead to respiratory obstruction or systemic effects from toxin absorption. It is diagnosed by isolating C. diphtheriae from infected sites and treated with antitoxin and antibiotics. Routine childhood immunization and booster shots have prevented diphtheria in developed nations, but it remains a risk without vaccination.

1. CORYNEBACTERIUM
ALLWYN VYAS G

2. INTRODUCTION
Corynebacterium (from the Greek koryne, club) are small and pleomorphic. The genus
Corynebacterium includes many species of aerobic and facultative Gram-positive rods.
The cells tend to have clubbed ends, and often remain attached after division, forming
“Chinese letter” or palisade arrangements. Spores are not formed. Growth is generally
Best under aerobic conditions on media enriched with blood or other animal products,
but many strains will grow anaerobically. Colonies on blood agar are typically small (1
to 2 mm), and most are non-hemolytic. Catalase is produced, and many strains form
acid (Usually lactic acid) through carbohydrate fermentation.
Corynebacterium genus is part of the CMNR group, a suprageneric group of the
Actinomycetales family, which includes several genera with high medical, veterinary
and biotechnological importance, like: Corynebacterium, Mycobacterium, Nocardia
and Rhodococcus. Bacteria from the CMNR group have in common:
(i) High G+C content and
(ii) A specific cell wall structure composed of mycolic acid, peptidoglycan and
arabinogalactan.
Corynebacterium genus was first created to harbor Corynebacterium diphtheriae and
other pathogenic species. Later on, other species were included, which differed in
shape, pathogenicity and sporulation. Nowadays, the genus is mainly composed of:
the non-pathogenic species Corynebacterium glutamicum and Corynebacterium
efficiens, which are of great biotechnological interest in amino acid production and
Corynebacterium variabile, a bacterium isolated from the micro flora contributing to
the development of flavor and texture in cheese ripening the opportunistic species
Corynebacterium jeikeium, Corynebacterium urealyticum and Corynebacterium
resistens, which are frequently associated with nosocomial infections and the
opportunistic and potentially pathogenic
Corynebacterium aurimucosum, which is mainly isolated from women with
urogenital infections and appears associated with complications in pregnancy and, the

3. pathogenic species Corynebacterium pseudotuberculosis, C. diphtheriae and
Corynebacterium ulcerans, of high veterinary and medical relevance, and a low
pathogenic potential bacterium, Corynebacterium kroppenstedtii, which is associated
with pulmonary disease and cases of mastitis.
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.
GENERAL CHARACTERISTICS
The principal features of the Corynebacterium genus were described by Collins and
Cummins 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 μms in length and 0.5 μms 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 facultative. 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.
CULTURE

4. Corynebacterium grows slowly, even on enriched media. In terms of 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 dentate borders that look similar to flowers
(C. gravis), or continuous borders (C. mitis), or a mix between the two forms
(C. intermedium)
PATHOGENECITY
Corynebacterium species occur commonly in nature in the soil, water, plants, and food
products. The non-diphtheiroid Corynebacterium species can even be found in the
mucosa and normal skin flora of humans and animals. 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. amicolatum, 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.

5. DIPHTHERIA
Diphtheria is a disease caused by the local and systemic effects of diphtheria toxin, a
potent inhibitor of protein synthesis. The local disease is a severe pharyngitis typically
accompanied by a plaque like pseudomembrane in the throat and trachea. The life-
threatening aspects of diphtheria are due to the absorption of the toxin across the
pharyngeal mucosa and its circulation in the bloodstream. Multiple organs are
affected, but the most important is the heart, where the toxin produces an acute
myocarditis.
EPIDEMIOLOGY
C. diphtheriae is transmitted by droplet spread, by direct contact with cutaneous
infections, and, to a lesser extent, by fomites. Some subjects become convalescent
pharyngeal or nasal carriers and continue to harbor the organism for weeks to months
or even for a lifetime. Diphtheria is rare where immunization is widely used. In the
United States, for example, fewer than 10 cases are now reported each year. These
usually occur as small outbreaks in populations that have not received adequate
immunization, such as migrant workers, transients, and those who refuse
immunization on religious grounds. It has been more than 20 years since any outbreak
exceeded 50 cases. Diphtheria still occurs in developing countries and in those places
where public health infrastructure has been disrupted. For example, in the former
Soviet Union, where the annual number of diphtheria cases had been below 200, over
47,000 cases and 1700 deaths occurred between 1990 and 1995. This outbreak
followed the introduction of diphtheria into a population where the immunization rate
for children was not sufficiently high, adults were not given boosters, and the efforts
at mass immunization early in the epidemic were inadequate.

6. PATHO GENESIS
C. diphtheriae has little invasive capacity, and diphtheria is due to the local and
systemic effects of DT, a protein exotoxin with potent cytotoxic features. It inhibits
protein synthesis in cell-free extracts of virtually all eukaryotic cells, from protozoa
and yeasts to higher plants and humans. Its toxicity for intact cells varies among
mammals and organs, primarily as a result of differences in toxin binding and uptake.
In humans the B subunit binds to one of a common family of eukaryotic receptors that
regulate cell growth and differentiation, thus exploiting a normal cell function. The
production of DT has both local and systemic effects. Locally, it’s action on epithelial
cells leads to necrosis and inflammation, forming a pseudomembrane composed
of a coagulum of fibrin, leukocytes, and cellular debris. The extent of the
pseudomembrane varies from a local plaque to an extensive covering of much of the
tracheobronchial tree. Absorption and circulation of DT allows binding throughout
the body. Myocardial cells are most affected; eventually, acute myocarditis develops.
The DT tox gene is regulated by a repressor protein (DtxR) in response to iron
limitation.
Toxin biosynthesis is greatest when the bacteria are grown at low iron concentrations.
Iron seems to play a central role in the expression of virulence; the repressor also
regulates a corynebacterial siderophore system and a number of other proteins.
Nontoxigenic strains of C. diphtheriae can produce pharyngitis, but not the toxic
manifestations of diphtheria. They can be converted to toxigenicity by lysogenization
in vitro with phage, and this process can probably occur in vivo.

7. PATHOGENECITY
After an incubation period of 2 to 4 days, diphtheria usually presents as pharyngitis or
tonsillitis. Typically, malaise, sore throat, and fever occur, and a patch of exudate or
membrane develops on the tonsils, uvula, soft palate, or pharyngeal wall. The gray-
white pseudomembrane adheres to the mucous membrane, and may extend from the
oropharyngeal area down to the larynx and into the trachea. Associated cervical
adenitis is common, and in severe cases cervical adenitis and edema produce a
“bullneck” appearance. In uncomplicated cases, the infection gradually resolves, and
the membrane is coughed up after 5 to 10 days.
The complications and lethal effects of diphtheria are caused by respiratory
obstruction or by the systemic effect of DT absorbed at the site of infection.
Mechanical obstruction of the airway produced by the pseudomembrane, edema, and
hemorrhage can be sudden and complete and can lead to suffocation, particularly if
large sections of the membrane separate from the tracheal or laryngeal epithelial
surface. The DT absorbed into the circulation causes injury to various organs, most
seriously the heart. Diphtheritic myocarditis appears during the second or third week
in severe cases of respiratory diphtheria.
It is manifested by cardiac enlargement and weakness, arrhythmia, and congestive
heart failure with dyspnea. Nervous system involvement appears later in the course of
disease, most often involving paralysis of the soft palate, oculomotor (eye) muscles,
or select muscle groups. The paralysis is reversible and is generally not serious unless
the diaphragm is involved. The disease resolves with the formation of antitoxin
antibody. C. diphtheriae may produce non-respiratory infections, particularly of the
skin.

8. The characteristic lesion which range from a simple pustule to a chronic, non-healing
ulcer, is most common in tropical and hot, arid regions. Cardiac and neurologic
complications from these infections are infrequent, suggesting that the efficiency of
toxin production or absorption is low compared to that in respiratory infections.
DIAGNOSIS
The initial diagnosis of diphtheria is entirely clinical. There are presently no rapid
laboratory tests of sufficient value to influence the decision regarding antitoxin
administration. Direct smears of infected areas of the throat are not reliable diagnostic
tools. Definitive diagnosis is accomplished by isolating and identifying C. diphtheriae
from the infected site and demonstrating its toxigenicity. Isolation is usually achieved
with a selective medium containing potassium tellurite (e. g, Tinsdale medium). It
should be recognized that while the diagnosis of diphtheria could be once be made
and confirmed with great confidence, it is now more difficult because experience with
the disease is rare. Most physicians have never seen a case of diphtheria, and most
laboratories have never isolated the organism and do not even stock the required
medium. Because routine throat culture procedures will not detect C. diphtheriae, the
physician must advise the laboratory of the suspicion of diphtheria in advance.
Generally, 2 days are required to exclude C. diphtheriae (i. e, no colonies isolated on
Tinsdale agar); however, more time is needed to complete identification and
toxigenicity testing of a positive culture.
TREATMENT
Specific treatment of diphtheria consists of antitoxic and antibiotic therapy. Anti-toxin
should be given immediately after diphtheria is suspected as the fatality rate increases
with delay in starting antitoxic treatment. The dosage recommended is 20000- 1lakh
units for serious cases, half the dosage being given intravenously. Antitoxin treatment
is generally indicated in cutaneous diphtheria as the causative strains usually non
toxigenic. C. diphtheria is sensitive to penicillin and can be cleared from the throat

9. within a few days by penicillin treatment. Diphtheria patients are given coarse of
penicillin though it only supplements and doesn’t replace antitoxin therapy.
Erythromycin is more active than penicillin in treatment of carriers.
PREVENTION
Before antibiotics were available, diphtheria was a common illness in young children.
Today, the disease is not only treatable but is also preventable with a vaccine. The
diphtheria vaccine is usually combined with vaccines for tetanus and whooping cough
(pertussis). The three-in-one vaccine is known as the diphtheria, tetanus and pertussis
vaccine. The latest version of this vaccine is known as the DTaP vaccine for children
and the Tdap vaccine for adolescents and adults.
The diphtheria, tetanus and pertussis vaccine is one of the childhood immunizations
that doctors in the United States recommend during infancy. Vaccination consists of a
series of five shots, typically administered in the arm or thigh, given to children at
these ages:
 2 months
 4 months
 6 months
 12 to 18 months
 4 to 6 years
The diphtheria vaccine is effective at preventing diphtheria. But there may be some
side effects. Some children may experience a mild fever, fussiness, drowsiness or
tenderness at the injection site after a DTaPshot. Ask your doctor what you can do for
your child to minimize or relieve these effects.
Rarely, the DTaP vaccine causes serious complications in a child, such as an allergic
reaction (hives or a rash develops within minutes of the injection), seizures or shock
— complications that are treatable.

10. Some children — such as those with epilepsy or another nervous system condition —
may not be candidates for the DTaP vaccine.
BOOSTER SHOTS
After the initial series of immunizations in childhood, you need booster shots of the
diphtheria vaccine to help you maintain immunity. That's because immunity to
diphtheria fades with time.
Children need their first booster shot at around age 12. The next booster shot is
recommended 10 years later and then repeated at 10-year intervals. Booster shots are
particularly important if you travel to an area where diphtheria is common.
The diphtheria booster is combined with the tetanus booster in one vaccine — the
tetanus-diphtheria (Td) vaccine. This combination vaccine is given by injection,
usually into the arm or thigh.
Doctors recommend that anyone older than age 7 who has never been vaccinated
against diphtheria receive three doses of the Td vaccine.
The Centers for Disease Control and Prevention also recommends a one-time
combined tetanus toxoid, reduced diphtheria and acellular pertussis (Tdap) vaccine
for adolescents around the age of 12 and for anyone older than that who hasn't
received the vaccine in the past — or doesn't know if they've received the vaccine. It's
also recommended for anyone who's pregnant, regardless of previous vaccination
status.

11. REFERENCES
 Ananthanarayan R, Paniker Jayaram C.K, Textbook Of
Microbiology, 8T H edition
 Atkinson, William (May 2012). Diphtheria Epidemiology and Prevention of
Vaccine-Preventable Diseases (12 ed.). Public Health Foundation.
 Kenneth J. Ryan, C. George Ray, Sherris Medical Microbiology, 6th edition
 Royer, Franklin (1905). "The Antitoxin Treatment of Diphtheria, with a Plea
for Rational Dosage in Treatment and in Immunizing".
 https://www.cdc.gov/diphtheria/
 http://www.healthline.com/health/diphtheria/