Corynebacterium spp and Related Organisms

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Corynebacterium spp and Related Organisms

• C. renale Group
• C. pseudotuberculosis
• C. ulcerans
• Arcanobacterium pyogenes
• C. diphtheriae

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Corynebacterium renale GroupC. renale, C.
pilosum, C. cystitidis

• Opportunistic urinary tractpathogens of ruminants
• cystitis
• ascending pyelonephritis
• Risk factors
• shortness of female urethra
• effects of pregnancy, parturition
• anatomic anomalies
• physical damage
• urinary tract obstruction
• Frequent relapses
• Venereal transmission

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Corynebacterium renale

• Flora of lower urogenital tract
• Most important member of the group
• cystitis, ascending pyelonephritis

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Clinical Presentation

• Pilus-mediated colonization
• Urease production gt ammonia production, mucosal
  inflammation
• Clinical presentation acute pyelonephritis
• fever, anorexia, polyuria, hematuria, pyuria
• abnormal posture (arched back)
• untreated infections become chronic
• weight loss, anorexia, decreased milk production

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Clinical Presentation

• Posthitis (pizzle rot, sheath rot) preputial
  ulcerative dermatitis
• high protein diets gt alkaline urine, excretion
  of urea
• action of urease gt ammonia
• result ulceration of preputial epithelium,
  secondary infections
• lesions spread to preputial mucosa gt crusting,
  swelling, pain
• pooled urine, purulent exudate inside prepuce gt
  necrosis
• sinus tracts drain through prepuce to skin
• chronic scarring of preputial orifice

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Corynebacterium renale GroupPathogenesis

• Corynebacterial attachment to urethral epithelium
• Ascending growth to bladder gt cystitis
• Ascending growth (vesiculourethral reflux) to
  kidney
• spreads chronically, relentlessly
• Virulence factors
• Pili
• piliated organisms more resistant to phagocytosis
  than nonpiliated
• Renalin (C. renale) extracellular cytolytic
  protein

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Corynebacterium pseudotuberculosisCaseous
lymphadenitis (CLA) in sheep and goats

• Chronic abscessation peripheral LN
• Thick caseous exudate, slightly greenish
• Economic losses
• deaths, carcass condemnations at slaughter
• decreased wool, milk production, value of hides
• decreased reproductive performance
• Direct contact shears, dip, feeders, feed
• Congregation of sheep during shearing, dipping
  aerosol transmission

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Pathogenesis

• Enter via skin wounds
• Phagocytosed (facultative intracellular parasite)
• Multiplies in phagolysosome, phagocytes die
• Permeability increases, spread to regional LN
• Abscesses primary, secondary sites
• May become metastatic ("thin ewe syndrome)

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Virulence Factors

• Cell wall lipid
• Toxic phospholipase D (PLD)
• antichemotactic, lethal for neutrophils
• complement depletion
• increased vascular permeability
• immunization against PLD limits movement of bugs
  from inoculation sites to regional LN, prevents
  lesion development

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Corynebacterium ulcerans

• Similar to C. pseudotuberculosis
• Human pharyngitis, bovine mastitis
• Produces PLD, can produce diphtheria toxin (DT)
• DT-producing isolates from mastitic bovine milk
• sporadic human cases associated with raw milk

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Arcanobacterium pyogenes

• Common inhabitant of mucus membranes of domestic
  animals
• Opportunistic pathogen, causes disease in most
  species, most systems
• Syndromes typically suppurative

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Major virulence factor pyolysin (PLO)
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(No Transcript)
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C. diphtheriae

• Gram , club-shaped, pallisades
• No spores no flagella
• Sometimes encapsulated

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Epidemiology

• Records back to 300 BC, recognized as specific
  disease in 1821
• epidemics among New World colonists, natives
• George Washington died of diphtheria at 67
• Controlled by vaccination
• lowered prevalence of vaccination
• AIDS (avoidance of needles), apathy
• epidemic disease in unprotected populations

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Pathogenesis

• Bugs lodge in throat, multiply
• Bacteria remain localized
• no blood culture positive
• typical disease is toxemia only
• Toxin produced
• kills surrounding cells
• more multiplication

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Pathogenesis

• Inflammation gt pseudomembrane
• fluid portion of exudate (mainly fibrin), cells
  coagulate on surface
• Membrane may cause blockage
• Death by suffocation
• Toxin diffuses via circulation
• cardiac, neurologic complications
• heart/respiratory damage, paralysis

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Diphtheria Toxin

• Secreted as single protein chain
• Cleaved to yield A/B chains, joined by SS bond
• A catalytic activity
• B receptor binding/ translocation activities
• receptor heparin-binding epidermal growth
  factor signaling system for cell growth and
  differentiation

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Diphtheria Toxin

• Uptake
• binding, endocytosis, translocation from
  endocytic vesicle (lower pH _at_ 5) to cytoplasm
  (extension into cytoplasm
• cleavage of bond, freeing of A chain
• Activity of A
• ADP-ribosylation of protein EF-2 (involved in
  chain extension during eucaryotic protein
  synthesis)
• Target modified histidine (diphthamide), present
  only in EF-2, specific role not known

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Regulation of Toxin Production

• Gene found usually on temperate phages
• Regulation by iron (lower iron higher tox)
• Controlling protein is DtxR
• iron-dependent repressor protein
• DtxR in presence of iron
• "iron bound form," binds to DNA in promoter
  region
• prevents binding of RNA polymerase to promoter
• no binding to promoter at low iron,
  transcription of gene
• DT may be produced to kill cells, release iron
  stores

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Immunization

• Passive from immune mother
• Toxoid introduced 1923 now widely used
• active immunization at early age
• Schick test local necrotic reaction to injection
  of toxin
• Carrier rate
• without immunization 5, with immunization 0
• Horse anti-DT for passive immunization,
  prophylaxis in outbreaks