Corynebacterium and other Gram-positive rods
미생물학교실
권 형 주
Corynebacterium : coryne, a club; bakterion, a small rod (a small, club-shaped rod)
C. Diphtheriae : diphthera, leather or skin (reference to the leathery membrane
that forms initially on the pharynx) –가죽피부, pseudomembrane 형성
Coryneform group : Corynebacterium and related genera
: non-spore-forming,
: non-acid-fast, Short-chain mycolic acids
: gram-positive rods
with a high guanine plus cytosine content.
: metachromatic granules
: catalase-positive
: Ferment carbohydrates
Gram stain of C. diphtheriae
Table. Characteristic properties of selected Coryneform genera
Genus
Catalase
Fermentation
/Oxidation
Motility
Cell Wall
Mycolic
Acids
Diamino
Acid
Gram Stain
Corynebacterium
+
Ferm/Oxid
-
+
meso-DAP
Club-shaped rods
Arcanobacterium
-
Ferm
-
-
Lysine
Irregularly shaped rods
Brevibacterium
-
Oxid
-
-
meso-DAP
Short coccobacilli
Oerskovia
-
Ferm
Variable
-
Lysine
Long branching rods
Turicella
-
Oxid
-
-
meso-DAP
Long rods
Corynebacterium species associated with human disease
Organism
Diseases
C. diphtheriae
Diphtheria (respiratory, cutaneous); pharyngitis and endocarditis
(nontoxigenic strains)
C. jeikeium (group JK)
Septicemia, endocarditis, wound infections, foreign body (catheter,
shunt, prosthesis) infections
C. urealyticum (group D2) Urinary tract infections (including pyelonephritis and alkaline-encrusted
cystitis), septicemia, endocarditis, wound infections
C. amycolatum
Wound infections, foreign body infections, septicemia, urinary tract
infections, respiratory tract infections
C. macginleyi
Eye infections
C. minutissimum
Wound infections, respiratory tract infections
C. pseudodiphtheriticum
Respiratory tract infections, endocarditis
C. pseudotuberculosis
Lymphadenitis, ulcerative lymphangitis, abscess formation
C. riegelii
Genitourinary tract infections (females)
C. striatum
Wound infections, respiratory tract infections, foreign body infections
C. ulcerans
Respiratory diphtheria
Corynebacterium diphtheriae
PHYSIOLOGY AND STRUCTURE
- Pleomorphic rod (0.3 to 0.8 × 1.0 to 8.0 μm)
: irregular shape
- Metachromatic granules(이염소체)
: rods stained with methylne blue
- 1- to 3-mm colonies are observed
on blood agar medium
- Subdivision
: belfanti, gravis, intermedius, mitis
PATHOGENESIS AND IMMUNITY
- Classic model of bacterial virulence.
- Toxicity in diphtheria : exotoxin secreted by the bacteria at the focus of infection
: tox gene – lysogenic bacteriophage (b-phage)
- The organism does not need to enter the blood to produce the systemic signs of disease
Diphtheria toxin : Two processing steps
(1) proteolytic cleavage of the leader sequence from the
tox protein during secretion from the bacterial cell; and
(2) cleavage of the toxin molecule into two polypeptides
(A and B) that remain attached by a disulfide bond.
This 58,300-Da protein is an
example of the classic A-B exotoxin.
- B subunit : receptor-binding region, translocation region
- receptor : heparin-binding epidermal growth factor
- A subunit : catalytic region
-Toxin entry : the toxin becomes attached to the host cells,
facilitating the movement of the catalytic
region into the cytosol.
- cytotoxicity : The A subunit terminates host cell protein
synthesis by inactivating elongation factor 2
(EF-2) – ADP-ribosylation
- Toxin synthesis regulation : chromosomally encoded element, diphtheria toxin
repressor (DTxR) - activated in the presence of high-iron concentrations
- tox gene : transduction, lysogenic bacteriophage (b-phage)
EPIDEMIOLOGY
Diphtheria : found worldwide
- Respiratory droplets or skin contact transmit
- Humans are the only known reservoir for this organism
-C. diphtheriae maintenance : asymptomatic carriage in the oropharynx or on the skin of
immune people (after either exposure to C. diphtheriae or immunization)
- uncommon in the United States as the result of an active immunization program
CLINICAL DISEASES
The clinical presentation of diphtheria
(1) the site of infection,
(2) the immune status of the patient,
(3) the virulence of the organism.
BOX 26-3. Corynebacterium diphtheriae: Clinical Diseases
Respiratory diphtheria: Multiply on epithelial cells (pharynx). Sudden onset with exudative
pharyngitis, sore throat, low-grade fever, and malaise; a thick pseudomembrane develops
over the pharynx; in critically ill patients, breathing obstruction, cardiac arrhythmia, coma, and
death can develop
Cutaneous diphtheria: A papule can develop on the skin that progresses to a nonhealing
ulcer (chronic); systemic signs can develop
Thick pseudomembrane : bacteria, lymphocytes, plasma cells, fibrin, dead cells
 tonsils, uvula, palate, nasopharynx, larynx
 system complication : myocarditis-> heart failure, cardiac arrhythmias, death
- Neurotoxicity  neuropathy
This child has diphtheria resulting in a thick gray
coating over back of throat. This coating can
eventually expand down through airway and, if not
treated, the child could die from suffocation CDC
LABORATORY DIAGNOSIS
The initial treatment of a patient with diphtheria is instituted on the basis of the clinical
diagnosis, not laboratory results, because definitive results are not available for at least a
week
Microscopy
- Metachromatic granules : stained with methylene blue
- appearance is not specific to C. diphtheriae, and interpretation of the smear requires
technical expertise
Culture
Specimens for the recovery : nasopharynx and the throat
- enriched blood agar plate and a medium developed specifically (e.g., cysteine-tellurite
agar, serum tellurite agar). Tellurite, Löffler's medium
Toxigenicity Testing
o Test for the production of exotoxin
: in vitro immunodiffusion assay (Elek test),
: a tissue culture neutralization assay using specific antitoxin,
: in vivo neutralization assay using guinea pigs injected subcutaneously with the isolate from
the patient.
o PCR-based nucleic acid amplication method
TREATMENT, PREVENTION, AND CONTROL
- Diphtheria antitoxin : neutralize the exotoxin before it is bound by the host cell.
- Antibiotic therapy : penicillin or erythromycin is also used
to eliminate C. diphtheriae and terminate toxin production
- After the patient has recovered, immunization with toxoid is required
: most patients fail to develop protective antibodies after a natural infection.
Prevention : children - five injections of diphtheria with pertussis and tetanus
antigens (DPT vaccine) at ages 2, 4, 6, 15 to 18 months, and at 4 to 6 years.
- Penicillin, erythromycin
Other Corynebacterium Species
Box 26-4. Summary: Other Corynebacterium Species
• Biology, Virulence, and Disease
- Gram-positive pleomorphic rods
- Some clinically important species require lipids such as Tween 80 for good growth
(e.g., C. jeikeium, C. urealyticum).
- Diphtheria A-B exotoxin may be carried by C. ulcerans and C. pseudotuberculosis.
- Urinary tract pathogens produce urease (e.g., C. urealyticum).
- Many species able to adhere to foreign bodies (e.g., catheters, shunts, prosthetic devices)
- Some species resistant to most antibiotics (e.g., C. amycolatum, C. jeikeium, C. urealyticum)
- Diseases include septicemia, endocarditis, foreign body infections, wound infections, urinary tract i
nfections, respiratory infections, including diphtheria.
• Epidemiology
- Most infections are endogenous (produced by species that are part of the host's normal bacterial
population on the skin surface and mucosal membranes).
• Diagnosis
- Culture on nonselective media is reliable, although growth may be slow, and media may require s
upplementation with lipids.
•Treatment, Prevention, and Control
- Treatment with effective antibiotics to eliminate the organism
- Removal of foreign body
Other Corynebacterium Genera
Table 26-2. Less Common Coryneform Gram-Positive Rods Associated
with Human Disease
Organism
Diseases
Arcanobacterium
Pharyngitis, cellulitis, wound infections, absces
s formation, septicemia, endocarditis
Brevibacterium
Septicemia, osteomyelitis, foreign body (cathe
ter, shunt, prosthesis) infections
Rothia
Endocarditis, foreign body infections
Tropheryma
Whipple disease