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Corynebacteria. Filename: Coryne.ppt. Outline. Microbes Corynebacterium ,Listeria, Erysipelothrix Diseases Diphtheria ,Listeriosis, Erysipeloid. Corynebacterium : Habitat. Skin upper respiratory tract GI tract Urogenital tract of humans. C. diphtheriae Diphtheria

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corynebacteria

Corynebacteria

Filename: Coryne.ppt

outline
Outline
  • Microbes
    • Corynebacterium,Listeria, Erysipelothrix
  • Diseases
    • Diphtheria,Listeriosis, Erysipeloid
corynebacterium habitat
Corynebacterium: Habitat
  • Skin
  • upper respiratory tract
  • GI tract
  • Urogenital tract of humans
cornyebacterium pathogens
C. diphtheriaeDiphtheria

C.pseudotuberculosishumans sheep, cattle, suppurative lymphadenitis

C. ulceranshumans pharyngitis

cattle -mastitis

C. haemolyticumpharyngitis cutaneous infection

C.pyogenes cattle, sheep, swine suppurative infection

C.pseudodiphtheriticumendocarditis

Cornyebacterium: Pathogens
c xerosis
C. xerosis

opportunistic infections

Group J K immunocompromised host

related organisms
Related Organisms

Listeria monocytogenes

    • Listeriosis
  • Erysipelothrix rhusiopathiae
    • Erysipeloid
diphtheria laboratory diagnosis
DiphtheriaLaboratory diagnosis
  • Speedy diagnosis
  • Differentiate from commensals
    • “diphteroids”
    • nose & throat
    • C. xerosis C. hofmanni
  • Throat swabs (confirmatory)
    • Blood Tellurite
  • Virulence test
corynebacterium
Corynebacterium
  • Aerobic gram + rods
  • -pleomorphic: club-shaped
  • -pallisades
  • -snapping cell division
  • -metachromatic granules
    • methylene blue stain
    • volutin: polyphosphate
cellular morphology
Cellular Morphology
  • Gram positive rods
  • “Snapping division”
  • Palisade cells
  • “Chinese letters”

Erysipelothrix

specialized media
Tellurite:

black colonies

Not diagnosticallly significant

tellurite inhibits many organisms but not C. diphtheriae

Loeffler

best colonial morphology

Dextrose horse serum (1887)

now Dextrose beef serum

Specialized media
blood tellurite
Blood tellurite
  • Selective & differential medium
  • Corynebacteria are resistant to tellurite
    • Reduced to tellurium
  • Forms deposit in colonies
    • Colonies appear dark
  • Biotypes
    • gravis, intermedius, mitis
corynebacterium biotypes
Corynebacterium Biotypes
  • C diphtheriaegravis
  • C diphtheriaeintermedius
  • C diphtheriaemitis
  • Helpful for epidemiological tracing
  • Culture identified by biochemical tests.
diphtheria1
Diphtheria
  • Nasopharyngeal diphtheria
    • Pharyngeal
    • Larygngeal
  • Cutaneous diphtheria
  • Systemic complications

DIAGNOSIS MUST BE CLINICAL!!!!

pharyngeal diptheria
Pharyngeal diptheria
  • Inflammation
    • similar to strept throat
  • Leucocytes
    • infiltrated
    • killed
    • embedded in fibrin clot
  • TOXIN !!
diphtheria symptoms
Diphtheria Symptoms
  • Pharyngitis
  • Hypoxia
    • Choking
    • “Garitillo”
  • Fever (103 F)
  • Lymphadenitis

All SIGNS & SYMPTOMS CAUSED BY TOXIN

diphtheria pseudomembrane
Diphtheria Pseudomembrane
  • No True membrane
  • Very few live cells
  • Deposit of dead cells and protein
pseudomembrane
COVERS

tonsils,

uvula,

palate

nasopharynx

larynx.

Pseudomembrane
  • CONTAINS
    • bacteria
    • lymphocytes
    • plasma cells
    • fibrin
    • dead cells
diphtheria systemic complications
DiphtheriaSystemic 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
virulence factors
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
diphtheriatoxin
DiphtheriaToxin
  • Blocks protein synthesis
  • Protein 63Kd
  • controlled by Tox gene
  • lysogenic phage Beta-corynephage
  • expressed if [iron] low
  • 2 components A-B
regulation of diphtheria toxin high fe 2
Regulation of Diphtheria Toxin High [Fe 2+]

NO Toxin Produced

P

o

tox

Corynebacteriophage beta

Fe 2+ + apo DtxR

[Fe 2+*DtxR]

p

dtxR

C diphtheriae

dtxR= repressor protein

regulation of diphtheria toxin low fe 2

P

o

tox

Corynebacteriophage beta

Regulation of Diphtheria Toxin Low [Fe 2+]

Toxin Produced!!!

Fe 2+ + apo DtxR

[Fe 2+*DtxR]

toxin
Toxin
  • Part A
    • Active site
    • N terminal
    • Enzyme
  • Part B
    • Binding site
    • Binds to membrane receptor
    • Transmembrane
diphtheria toxin part a
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
diphtheria toxin part b
Diphtheria Toxin: Part B
  • Binding Site
  • Binds to cell receptor
  • Bound receptor internalized
  • Endosome
    • Hydrolysed by protease
    • Disulfide broken
    • Part A released
toxingenicity tests
Toxingenicity Tests

In Vitro Elek test

In Vivo Animal inoculation

rabbit skin test-necrosis

guinea pig challenge test- lethal

low [Fe 2+] induces toxin

animal inoculation
Animal inoculation

Inject 2 mice with 5ml C.diphtheria cells

one mouse protected with 1000 units C.diphtheriae antitoxin

Autopsy - adrenals hemorrhagic

control
Control
  • Immunization diphtheria toxoid
  • Schick test
    • check for antibodies
  • Passive immunity
    • Antibodies
  • Antibiotics
    • Penicillin & erythromcyin
epidemics
Epidemics
  • Immune individuals
    • may be carriers
    • antibiotics
  • Non immune individuals
    • Exposed
      • passive immunity antibodies
    • Not exposed
      • immunize with toxoid
diphtheria in the soviet union and nis
Diphtheria in the Soviet Union and NIS

Emerging infectious diseases: 4(4) 1998 Vitek & Wharton

performance objectives

Performance Objectives

Key terms, concepts

short answers

key terms1
Schick test

Elek Test

Diphtheria toxin

larnygeal diphtheria

pharyneal diphtheria

Key Terms
key organisms
Corynebacterium

Listeria

Erysipelothrix

Key Organisms
epidemiology of diphtheria
Epidemiology of Diphtheria
  • Disease/bacterial factors
  • Transmission
  • Who is at risk
  • Geography/ season
  • Incidence
  • Modes of control
short answers
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.