Lecture 30 - Vibrio cholerae Flashcards
(19 cards)
list the 4 key areas and global epidemiology of v cholerae
- east mediterranean, sub saharan africa, india, SE asia
- global increase to 1 mil cases from 2021-24
what are the 2 patterns of disease in v cholerae?
- endemic = seasonal outbreaks, <5yo
- epidemic = new strains, all ages, more severe, natural disasters
what is the incubation and clinical features of v cholerae?
- 18h-5day incubation
- rice water diarrhoea, death from dehydration/electrolyte imbalance
describe the history of v cholerae
- 7 pandemics 1817-1961 ongoing
- classic biotype caused 6 vs el tor biotype caused 7th
- classic -> el tor from sequential virulence mutations
- john snow = water pump as source in london
- pacini dicovered it
- koch cultured it
what are the 3 risk factor groups for v cholerae?
- large 10^8 infectious dose
- blood group O, immune status, gastric acidity
- environ = climate, sanitation, water supply
what are the 3 distinguishing features of v cholerae for acquiring pathogenesis?
- genetic exchange between strains/species
- rapid mod of gene expression from external stimuli
- toxins
describe v cholerae
- G-ve, single flagellum, comma shaped
- HGT = transformation, transduction, conjugation
- 2 chromosomes with Chr2 = domesticated
- super integrons = 179 cassetts many virulence
what is v cholerae’s typical niche and how is it transmitted to humans?
- saline coastal waters in zooplankton and shellfish
- humans ingest shellfish/water then spread to other humans by faecal-oral
what is the function of v cholerae’s T6SS?
- shellfish chitin promotes transformation competence by T6SS
- T6SS kills surrounding cells and steals DNA by transformation = acquire virulence
where and how does v cholerae colonise?
- gut mucosal epithelia, no invasion
- flagellum for mvmt then cholera toxin coregulated pilus (TcpA) for adhesion
how does v cholerae acquire TcpA?
- vibrio PAI (VPIΦ) from phage
- TcpA as receptor for cholera toxin (CT) phage CTX Φ
describe the 5 step mechanism of the cholera toxin
- active A + 5x binding B ring binds ganglioside receptors (GM1) on intestinal epithelia
- endocytosed to endo retic
- major A subunit CT-A1 dissociates from B ring, enters cytosol, acitivates Gsalpha subunit of guanine nucleotide binding reg protein (Galphas)
- Locks adenylate cyclase in active state = increased cyclic AMP (cAMP)
- cAMP activates protein kinase A (PKA) = inhibits NaCl absorption by Na/H exchanger (NHE) = increased Cl- and bicarb export = water loss
what are the 2 host susceptibility factors for v cholerae?
- Blood group A = low CT affinity = CT removed by peristalsis vs H antigens in blood group O bind CT strongly
- Secretors = blood group antigens expressed on intestinal epithelia
how is v cholerae’s expression regulated? which genes are regulated?
- quorum sensing in LuxOP system
- TcpA, CTX and other VFs
- increased expression @ low cell density
what are the 2 serogroups associated with pathogenic v cholerae?
- serogroup O1 = classic and el tor biotypes = all 7 pandemics
- serogroup O139 mutated from O1 El tor = 1992 asian epidemic
what were the 4 main WGS results of v cholerae?
- el tor and classic = distinct = evolved separately
- environ strains different from pandemic strains
- el tor = clonal, single source, independent global spread
- classical more diverse than el tor
how is v cholerae prevented?
sanitation, municipal water systems, oral inactivated cholera toxin B subunit vaccine
how is v cholerae treated?
fluid replacement, antibiotics to reduce stool volume and shedding, Zn for young
how are outbreaks of v cholerae managed?
safe drinking water, sanitation, hygiene, vaccine stockpiles
