Corynebacteria
Filename: Coryne.ppt
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Outline
 Microbes
– Corynebacterium,Listeria,
Erysipelothrix
 Diseases
– Diphtheria,Listeriosis,
Erysipeloid
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Corynebacterium: Habitat
 Skin
 upper
respiratory tract
 GI tract
 Urogenital tract of humans
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Cornyebacterium: Pathogens
 C.
diphtheriae
Diphtheria
 C.pseudotuberculosis
humans sheep, cattle,
suppurative
lymphadenitis
 C. ulcerans humans
pharyngitis
cattle -mastitis
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 C.
haemolyticum
pharyngitis cutaneous
infection
 C. pyogenes cattle,
sheep, swine
suppurative infection
 C.pseudodiphtheriticum
endocarditis
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C. xerosis
opportunistic infections
Group J K
immunocompromised host
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Related Organisms
Listeria monocytogenes
– Listeriosis
 Erysipelothrix
rhusiopathiae
– Erysipeloid
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Diphtheria
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Diphtheria
Laboratory diagnosis
 Speedy
diagnosis
 Differentiate from commensals
– “diphteroids”
– nose & throat
– C. xerosis C. hofmanni
 Throat
swabs (confirmatory)
– Blood Tellurite
 Virulence
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test
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Corynebacterium
 Aerobic
gram + rods
 -pleomorphic: club-shaped
 -pallisades
 -snapping cell division
 -metachromatic granules
– methylene blue stain
– volutin: polyphosphate
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Cellular Morphology
 Gram
positive rods
 “Snapping division”
 Palisade cells
 “Chinese letters”
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Erysipelothrix
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Specialized media
Tellurite:
black colonies
Not diagnosticallly
significant
tellurite inhibits many
organisms but not C.
diphtheriae
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Loeffler
best colonial morphology
Dextrose horse serum
(1887)
now Dextrose beef serum
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Blood tellurite
 Selective
& differential medium
 Corynebacteria are resistant to
tellurite
– Reduced to tellurium
 Forms
deposit in colonies
– Colonies appear dark
 Biotypes
– gravis, intermedius, mitis
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Corynebacterium Biotypes
C
diphtheriae gravis
 C diphtheriae intermedius
 C diphtheriae mitis
 Helpful for epidemiological tracing
 Culture identified by biochemical tests.
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Diphtheria
 Nasopharyngeal
diphtheria
– Pharyngeal
– Larygngeal
 Cutaneous
diphtheria
 Systemic complications
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DIAGNOSIS MUST BE CLINICAL!!!!
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Pharyngeal diptheria
 Inflammation
– similar to strept
throat
 Leucocytes
– infiltrated
– killed
– embedded in fibrin
clot
 TOXIN
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!!
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Diphtheria Symptoms
 Pharyngitis
 Hypoxia
– Choking
– “Garitillo”
 Fever
(103 F)
 Lymphadenitis
All SIGNS & SYMPTOMS CAUSED BY TOXIN
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Diphtheria Pseudomembrane
 No
True
membrane
 Very few live
cells
 Deposit of dead
cells and
protein
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Pseudomembrane
 CONTAINS
–
–
–
–
–
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bacteria
lymphocytes
plasma cells
fibrin
dead cells
 COVERS
– tonsils,
– uvula,
– palate
– nasopharynx
– larynx.
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Diphtheria
Systemic complications
 Nerves
– toxic peripheral neuropathy
– paralysis of short nerves
– mouth, eye, facial extremities
 Cardiac
– Congestive heart failure
– high amount of toxin 48-72 hours
– Low amount of toxin 2-6 weeks
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Virulence Factors
 Diphtheria
toxin !!!
– blocks protein synthesis
 Dermonecrotic
toxin
– sphingomyelinase
– increases vascular permeability
 Hemolysin
 Cord
factor -Toxic trehalose
– corynemycolic acid, corynemyolenic acid
– 6,6’-di-O-mycoloyl- a,a’-D-trehalose
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DiphtheriaToxin
 Blocks
protein synthesis
 Protein 63Kd
 controlled by Tox gene
 lysogenic phage Betacorynephage
 expressed if [iron] low
 2 components A-B
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Regulation of Diphtheria Toxin
High [Fe 2+]
NO Toxin Produced
P
o
tox
Corynebacteriophage beta
[Fe 2+ *DtxR]
Fe 2+ + apo DtxR
p
dtxR
C diphtheriae
dtxR= repressor protein
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Regulation of Diphtheria Toxin
Low [Fe 2+]
Toxin Produced!!!
P
o
tox
Corynebacteriophage beta
[Fe 2+ *DtxR]
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Fe 2+ + apo DtxR
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 Part A
– Active site
– N terminal
– Enzyme
 Part
Toxin
B
– Binding site
– Binds to
membrane
receptor
– Transmembrane
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Diphtheria toxin: Part A
 Active
site
 Enzyme
 Blocks protein synthesis
– ADP-ribosyl transferase
– elongation factor 2 (EF2)
 Specific
for mammalian cells
– Prokaryotes have different EF2
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Diphtheria Toxin: Part B
 Binding
Site
 Binds to cell receptor
 Bound receptor internalized
 Endosome
– Hydrolysed by protease
– Disulfide broken
– Part A released
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Activation of Diphtheria Toxin
A
A
B
B
B
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A
B
A
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Toxingenicity Tests
In Vitro Elek test
In Vivo Animal inoculation
rabbit skin test-necrosis
guinea pig challenge test- lethal
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low [Fe 2+] induces toxin
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Elek test
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Animal inoculation
Inject 2 mice with 5ml C.diphtheria cells
one mouse protected with 1000 units
C.diphtheriae antitoxin
Autopsy - adrenals hemorrhagic
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Control
 Immunization
 Schick
diphtheria toxoid
test
– check for antibodies
 Passive
immunity
– Antibodies
 Antibiotics
– Penicillin & erythromcyin
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Schick Test for Diptheria
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Epidemics
 Immune
individuals
– may be carriers
– antibiotics
 Non
immune individuals
– Exposed
passive immunity antibodies
– Not exposed
immunize with toxoid
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Diphtheria: Russian Federation
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Diphtheria in the Soviet Union and NIS
Emerging infectious diseases: 4(4) 1998 Vitek & Wharton
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Diphtheria Incidence
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Diphtheria in the Russian Federation
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The End
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Performance Objectives
Key terms, concepts
short answers
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Key Terms
 pseudomembrane
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Key Terms
 Schick
test
 Elek Test
 Diphtheria toxin
 larnygeal diphtheria
 pharyneal diphtheria
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Key Organisms
 Corynebacterium
 Listeria
 Erysipelothrix
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Key Concepts
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Epidemiology of Diphtheria
 Disease/bacterial
factors
 Transmission
 Who
is at risk
 Geography/ season
 Incidence
 Modes of control
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Short Answers
 Construct
a table of the virulence factors
associated with diphtheria and the biological
activity of each
 Use a series of no more than four diagrams to
describe the mechanism of action of
diphtheria toxin
 Describe the clinical manifestations of
diphtheria
 Construct a table listing the common
Corynebacteria and the associated diseases.
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