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MICR3330 > 26 - Vibrio cholerae > Flashcards

26 - Vibrio cholerae Flashcards

1
Q

Clinical features of cholera

A
  • Incubation 18h to 5 days
  • Very severe watery diarrhoea (rice water stool)
  • Death due to dehydration or electrolyte imbalance
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2
Q

Two patterns of disease

A

Endemic or epidemic

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3
Q

Endemic disease

A
  • Seasonal outbreaks
  • Children most at risk (no pre existing immunity)
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4
Q

Epidemic disease

A
  • Intro of new infection or strain
  • All ages
  • More severe
  • Linked to natural disasters
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5
Q

Spread of cholera

A
  • Faeco oral spread
  • Often within families
  • Asymptomatic shedding common, leading to contamination of water supply
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6
Q

Vibrio cholerae

A
  • Gram negative comma shaped with flagellum
  • Horizontal gene transfer important - 2 chromosomes (Ch2 is ‘domesticated plasmid’)
  • Contains super integron
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7
Q

Horizontal gene transfer

A
  • Naturally competent (transformation)
  • Frequently infected by phages (transduction)
  • Multiple plasmids (conjugation)
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8
Q

Super integron

A

Large integron with 179 cassettes, many of which encode virulence determinants

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9
Q

Integron

A

Genetic elements with the ability to capture genes (into expression cassette), including those encoding antibiotic resistance or virulence factors by site specific recombination

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10
Q

Ecology

A
  • Saline coastal waters and estuaries
  • Lives in association with zooplankton and shellfish
  • During periods of nutrient deficiency –> viable, non-culturable form in biofilms
  • Favourable conditions (zooplankton bloom) –> proliferate –> humans ingest water
  • Outbreaks occur through faecal contamination of water
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11
Q

Chitin from shellfish

A

Induces competence for transformation

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12
Q

V. cholerae T6SS

A
  • Uses as a weapon to kill surrounding bacteria and ‘steal’ their DNA by transformation
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13
Q

Three distinguishing characteristics

A
  • Key role for genetic exchange between strains/species
  • Rapid modulation of gene expression in response to external stimuli
  • Toxin production
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14
Q

Process of colonisation

A
  • Colonises the gut mucosa, does not invade
  • Flagellum moves the bacteria towards the epithelial surface
  • Cholera toxin coregulated pilus (TcpA) mediates attachment to mucosa
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15
Q

Acquisition of cholera toxin

A
  • Non-pathogenic strains are infected by a bacteriophage (Vibrio Pathogenicity Island phage - VPIΦ)
  • VPIΦ encodes TcpA
  • TcpA then acts as receptor for a second bacteriophage, CTX Φ
  • CTX Φ has genes for cholera toxin (CTX)
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16
Q

Pathway of cholera toxin

A
  • Single toxic active A subunit attached to a ring of five identical cell-binding B subunits
  • B subunits bind to the epithelial cell surface receptor, ganglioside GM1
  • Toxin is endocytosed and transported to ER
  • CT-A1 dissociates from B pentamer to enter cytosol, where is activates the Gsα subunit of guanine nucleotide-binding regulatory protein
  • This reaction locks adenylate cyclase in an activated state, resulting in enhanced cyclic AMP (cAMP) production.
17
Q

End result of cholera toxin pathway

A
  • cAMP activates protein kinase-A (PKA).
  • Activation of PKA inhibits NaCl absorption through Na+/H+ exchanger, with decrease in sodium uptake and an increase in chloride and bicarbonate export.
  • Water follows this ion gradient
    to produce a net fluid loss.
18
Q

Host genetics and susceptibility to cholera

A

Cholera toxin (CT) interaction with host cells depends on the person’s blood group and secretor status

19
Q

Role of blood group and secretor status in cholera

A
  • In ‘secretors’, blood group antigens are expressed on intestinal epithelial cells.
  • Blood group A-antigens have a low affinity for CT, and CT is therefore more easily ejected by the peristaltic movement of the intestine.
  • Therefore secretors with blood group A are protected from severe disease
  • Group O can bind CT strongly, therefore individuals with blood group O have a high risk of severe disease
20
Q

Quorum sensing in regulation of virulence factor expression

A
  • Expression of TcpA, CTX and several other virulence, factors is under quorum sensing control.
  • Expression is increased at low cell density and repressed at high cell density
21
Q

which group of cholera has caused all pandemics

A

Serogroup O1

22
Q

Prevention

A
  • Sanitation infrastructure, municipal water systems
  • Oral vaccines incorporating inactivated V. cholerae +/-toxin B subunit
23
Q

Treatment

A
  • Fluid replacement
  • Antibiotics
  • Zinc for young children
24
Q

Outbreak management

A
  • Safe drinking water, sanitation hygiene
  • Vaccination stockpiles

MICR3330 (29 decks)

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