Two serogroups
O1
O139
Which serogroup causes majority of outbreaks
O1
Type of bacteria
- gram -ve
- motile
- comma shaped curved rod
- single polar flagellum
How many serogroups are there
200
How can serogroup 01 be subdivided
Classical
El Tor
Features of clinical strains of serogroups 01 El Tor
Haemolytic
Polymyxin B resistant
How does cholera exist
As natural flora in aquatic ecosystems
Transmission route
Oral route
- contaminated water
Two isolates with a close relationship
Haitian El Tor01 and Bangladesh
Vehicle for transmission
Diarrhea
Incubation period
1 to 3 days
Symptoms
Vomiting
Muscle cramps
Watery diarrhea
Consequences of severe diarrhea
dehydration
electrolyte imbalance
*loss of 20L water/day
Serious symptoms
circulatory collaps -> HF
Survival of acute disease leads to
recovery with immunity
(some potential to carry and shed the pathogen)
Treatments
- oral/ IV hydration
- prompt restoration of lost fluids and salts
- in conjunction with hydration, treatment with Abs
- doxycycline - adults
Mechanism of action of Doxycycline
Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit
Composition of cholera hexameric enterotoxin
1 A chain and 5 B chain
Toxic component
A chain
What receptor does cholera toxin bind to?
GM1 ganglioside receptor
*located on surface of intestinal epi cells
MOA of cholera toxin
Binds to GM1 receptor, retrograde endocytosis, Gsa binds to Ac, acticates cAMP, Cl ions efflux via CFTR
*Na, H30- and H20 alss efflux into lumen -> watery diarrhea
Innate Immune response to V.C
- v.c disrupts mucosal barrier which widens intracellular spaces, disrupting apical junction
- influx of NFs, macrophages, APCs and lymphocytes into lamina propia
- production of effector molecules at mucousal surface (lactoferrin, defensins, oxidases)
- increase in expression of ROS proteins (DUOX2) (iNOS)
- activation of NLRP3 inflammasome and type I IFN
- APCS produce cytokines (IL1B, IL6, IL17)
Adaptive Immune Response to V.c
- long-lasting immunity
- protection by specific IgA Abs
Primary virulence factor of V.c
enterotoxin
