Lecture 3 revision Flashcards
What bacterium causes cholera
Vibrio cholerae, a gamma proteobacterium
Explain V. cholerae
- Causative agent of cholera in human intestines
- Disease occurs at mucosal surface - no invasion into deeper tissue
- Disease primarily caused by cholera toxin
Background of cholera history
- First described in Ganges Delta
- Earliest description from 9th century Tibet
- Confined to India until 19th Century
- Seven pandemics
Seven cholera pandemics
- India origins as early as 1563
1817-23 - first pandemic
1829-50 - second pandemic
1852-60 - third pandemic
1863-79 - fourth pandemic
1881-96 - fifth pandemic
1899-1923 - sixth pandemic
1961-? - seventh pandemic
1991-? - South America
7th pandemic spread
- From Indonesian Archipelago (1961), cholera spread to West Pacific and South East Asia (1970-1971)
- Cholera spread to Africa, Europe and Middle East (1970-1971)
- Cholera spread to Latin America (1991)
- Cholera spread to Haiti and Dominican republic
What two events caused spikes in Cholera from 2000-2021
Haitian earthquake in 2011
Yemen war in 2017
Where are the most affected places in 2024
Central and East Africa
Southern Asia
Case fatality ratio increased again in 2020 (most likely due to COVID)
Causative agent discovery
John Snow at broad street pump - first epidemiological and geographical analysis
Cholera was transmitted via water (1855)
In 1854:
Breakout in Soho, London
120 deaths in three days
Location of deaths clusteredf round a pump on Broad Street
Pump taken out of service and epidemic ended
Theory that cholera is spread by dirty water
Filippo Pacini
1854: Cholera reaches Florence
Pacini discovers causative agent
Ignored due to predominance of miasma theory
Robert Koch
1884 - Vibrio cholerae rediscovered and identified
Previously isolated by Pacini in 1854
Koch was unaware of Pacini’s discovery and his greater pre-eminence allowed the discovery to be widely spread for other benefit
In 1965, bacterium was formally renamed Vibrio cholerae Pacini 1854
Physiology of V. cholerae
Gram negative
Facultative anaerobe
Curved rod (1.4-2.6um x 0.5-0.3um)
Asporogenous
Growth stimulated by NaCl
pH 6-10, acid liable
Temp - 18-37 degrees
Polar monotrichous
Can enter viable, non-culturable state
V. cholerae serotypes
Differences in lipopolysaccharide sugar composition (O-antigen)
Outbreaks caused by O1 or O139
O1 causes majority of outbreaks
O139 identified in Bangladesh in 1992 - confined to south east asia
Diagram of V. cholerae classification
O1 or O139
O1 has two biotypes: Classical and El Tor
Inaba (A and C), Ogawa (A and B) and Hikojima (A, B and C)
The environment of V. cholerae
Found in costal water or estuaries (free living)
Often associated with zooplankton (micro and macro), macroalgae, phages and shellfish, and uses chitin as carbon and nitrogen source.
- Autotrophic microplankton and macrozooplankton eaten by fish
- Macroplankton and fish spread it to waterfowl
Seasonal vibrio
As temperature rises, more algae blooms and zooplankton
Causes more V. cholerae prevalence
Where is seasonal plankton associated
Plankton blooms correlate with cholera occurrence in Bangladesh
V. cholerae:
- Attach to crustacean zooplankton
- Secrete chitinase enzymes
- Metabolically active even in high acidic environments and don’t lose viability or virulence
- Chitin during blooms plays role in aquatic life cycle of V. cholerae, and seasonal transmission of cholera
Pathogenicity of V. cholerae genome
Two chromosomes
First chromosome: 2.96 Mbp
Has EPS, OriC1, dnaA, VPI (attachment pilus), toxR and CTXphi (Enterotoxin)
VP1 and CTXphi inserted by virus
Second chromosome: 1.07 Mbp
Has oriCii, hlyA, integron island, and hap
Ingestion of V. cholerae
Ingestion of V. cholerae
Resistant to gastric acid at 10^2-10^3 when buffered in food, and 10^10 when not buffered in food
Colonize small intestine
Virulence factors of V. cholerae
CTX prophage/cholera toxin
VPI-1-toxin-coregulated-pilus
AI-1/2/CAI-1 - Quorum sensing
Quorum sensing of V. cholerae
- Cell-to-cell communication to precisely control pathogenicity and biofilms:
- Production of colonization factors and toxins in human host, forming biofilms
- Genetic exchange
- Cellular processes where at least four sensory inputs function in parallel to regulate V. cholerae QS
Any one of these pathways is sufficient colonisation
Replies on secretion and detection of autoinducers:
Low cell density - expression of virulence factors forms biofilms
High cell density - accumulation of two QS autoinducers represses these traits
- CAI-1 and AI-2 function synergistically to control gene expression
- CAI-1 is stronger
Early vs late infection of V. cholerae
early:
Biofilm dispersal
virulence genes induced
mucosal peneration
Antivirulence genes repressed
late:
virulence genes repressed
late induced genes induced
quorum sensing on
Mucosal escape
Priming for environmental entry
V. cholerae pathway at low cell density
LuxPQ, cqsS, cqsR, and VpsS are predominated by kinase activites
Low levels of AI-2 and CAI-1
LuxU activated
LuxO-P activated
Orr1-4 small RNAs produced via transcription
AphA formed via translation and biofilms form
HapR not formed
V. cholerae pathway at low cell density
LuxPQ, cqsS, cqsR, and VpsS are predominated by deophosphorylation activites
High levels of AI-2 and CAI-1
LuxU not activated
LuxO not activated
Qrr1-4 not formed via transcription
AphA not formed, whilst HapR is
