Lecture 3 - Cholera Flashcards
What pathogen causes cholera
Vibrio cholerae
Taxonomy of Vibrio CHloerae
Domain: Bacteria
Phylum: Proteobacteria
Class: γ - proteobacteria
Order: Vibrionales
Family: Vibrionaceae
Genus: Vibrio
Species: Vibrio cholerae
What is V. cholerae
- Causative agent of human intestinal disease cholera
- Occurs at mucosal surface, no invasion of microbe into deeper tissue
- Symptoms cause primarily by cholera toxin
Background of Cholera
- First described in Ganges Delta
- Earliest description in 9th century Tibet
- Confined to India until 19th century
- Seven pandemics to date
History of Cholera
Origins in India (early as 1563)
7 pandemics to date:
- 1817-23 - first pandemic
(India to South, Central Asia, Middle East and Russia)
1829-50: Second Pandemic (reaches England)
1852-60: Third Pandemic* Pacini
1863-79: Fourth Pandemic
1881-96: Fifth Pandemic * Koch
1899-`1923: Sixth Pandemic
1961-?: Seventh Pandemic
1991-?: South America
What is a pandemic?
A pandemic is an epidemic of infectious disease that has spread through human populations across a large region; for instance, multiple continents, or even worldwide
Seventh pandemic
1961-?
From Indonesian Archipelago (1961), cholera spread to Western Pacific and South East Asia (1962-1965);
Cholera spread to Africa, Europe, Near and Middle East (1970-1971);
Cholera spread to Latin America (1991);
Cholera spread to Haiti and Dominican Republic (2010).
Most common affected areas
Primarily Africa, some of southern and south east Asia
Discovery of Causative agent
John Snow (1813-1858): BROAD STREET PUMP
Water borne transmission of cholera (1855)
In 1854 there was a massive cholera outbreak in Soho, London
in 3 days over 120 people died from the disease.
Snow plotted the locations of the deaths on a map and found they clustered around a pump in Broad Street
he suggested that the pump be taken out of service – thus helping to end the epidemic.
theory of the spread of cholera by dirty water.
Broad street pump
Snow’s analysis if famous because:
1. First epidemiological analysis of disease - trying to understand the spread of cases by different environmental factors
- The first geographical analysisof disease data – plotting points on a map and looking for relationships
Filippo Pacini (1812-1883)
1854: Cholera reaches Florence, Italy
Pacini discovers causative agent
Ignored due to predominance of miasma theory of disease
Robert Koch (1843-1910)
1884: Re-discovers Vibrio cholerae
Identified the Vibrio bacterium that caused cholera
-never managed to prove it
Previously isolated by Italian anatomist Filippo Pacini
in 1854
Koch was unaware of Pacini’s work and made an independent discovery, and his greater pre-eminence allowed the discovery to be widely spread for the benefit of others.
In 1965, however, the bacterium was formally renamed Vibrio cholerae Pacini 1854.
Physiology of V. cholerae
- Facultative anaerobe, gram-negative
- Curved rod (1.4-2.6um x 0.5-0.3um)
- Asporogenous
- Growth stimulated by NaCl
- pH 6-10, acid liable
Temperature 18-36 degrees celcius
Polar monotrichous (sheathed)
Can enter viable, but non culturable state
Serotypes
Differences in the sugar composition of the heat-stable surface somatic “O” antigen
Outbreaks: 2 serogroups of V. cholerae, O1 and O139,
O1 causes the majority of outbreaks
O139 – first identified in Bangladesh in 1992 – is confined to South-East Asia.
Environment of V. cholerae
- Found in coastal waters and estuaries (free living)
- Often associated with zooplankton and shellfish in water, and it can use chitin as a carbon and nitrogen source
Vibrio cholerae and zooplankton
Seasonal plankton blooms correlate with occurrence of cholera in Bangladesh.
Vibrio cholerae
found attached to chitin of crustacean zooplankton.
can secrete chitinase enzymes (a potential nutrient source?).
remain metabolically active even in a high acidic environment without losing either viability or virulence.
the abundance of chitin that occurs during blooms plays an important role in the aquatic life cycle of V. cholerae and, ultimately, in the seasonal transmission of cholera.
Genome of Vibrio cholerae
Two chromosomes
chromsome I:
2.96Mb
housekeeping genes
Encodes genes for enterotoxins (CTXφ) and attachement pilus (VPI)
Chromosome 2:
1.07Mb
Contains integron island
Virulence and pathogenicity
Ingestion of V. cholerae
->
(infectious dose: 10^2-10^3 buffered in food, 10^10 when non-buffered) Resistant to gastric acid
->
Colonize small intestine
Virulence factors
CTX phophage/cholera toxin
VPI-1-toxin-coregulated pilus
Quorum sensing (AI-1/2/CAI-1)
Vibrio cholerae (quorum sensing)
Vibrio cell-to-cell communication to precisely control pathogenicity and biofilms
- Produces colonization factors and toxins in host, biofilm formation
- Genetic exchange
- Important cellular processes
- At least four sensory input function in parallel to regulate V. cholerae QS
- Any one of these communication pathways is sufficient colonisation
Relies on the secretion and detection of signalling molecules (autoinducers).
Low cell density: expression of virulence factors and forms biofilms.
At high cell density the accumulation of two QS autoinducers represses these traits.
CAI-1 and AI-2, function synergistically to control gene regulation.
CAI-1 is the stronger of the two signals.
Autoinducers vs V. cholerae
LuxPQ
CqsS
CqsR
VpsS
Kinase activites predominate:
- Autoinducer activate response regulator (LuxO) by activating LuxU
LuxO promotes transcription of four small RNAs called Qrr1-4
This causes translation of AphA and inhibits HapR
Infection by V. cholerae
Secrete enterotoxin
->
Enterotoxin binds intestinal cells
->
Chloride channels activated
->
Release large quantities of electrolytes and bicarbonates
->
Fluid hypersecretion
->
Diarrhea
->
Dehydration
Virulence of V. cholerae
The genes for cholera toxin are carried by CTXphi (CTXφ), a temperate bacteriophage inserted into the V. cholerae genome.
CTXφ can transmit cholera toxin genes from one V. cholerae strain to another via horizontal gene transfer
Transduction, conjugation, transformation (enhanced by chitin).
A5B exotoxin (A comprises 2 subunits)
The genes for toxin coregulated pilus are coded by the VPI pathogenicity island (VPIφ).
How does V. cholerae enter?
Fecal-oral route
Entry = oral
Discharge = fecal
Person-to-person – possible (indirect)
Food
Water
Alkaline foods)
Fruit/Veg
Carriers: houseflies and other insects
