4. Continue….
Folates in human
Folate deficiency neural tube defects.
Potential interactions with gut bacteria.
Inhibiting Escherichia coli folate biosynthesis
treatment with drug sulfamethoxazole (SMX)
mutation of the PABA synthesis pathway
(e.g., a pab A mutant)
5. Continue….
sufficient folate available to support normal growth of both
organisms.
Developed a C. elegans folate deficiency model, a mutant in gcp-2.1
and homologue of human GCPII( polyglutamated folates).
C. elegans gcp-2.1 grow on SMX-treated E. coli.
worms show delayed development and infertility.
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External media, microbe and animal can be carefully controlled.
E. coli represents an Important alternative route
bacterial toxicity.
7. Methods
E. coli preparation and growth assay
diluted with
M9 in a cuvette
A
spectrophotometer
was used to read
bacterial growth
Bacterial growth
was calculated
by multiplying
OD600
homogenized
solution.
overnight LB
culture of E. coli
was transferred into
DM.
• ΔabgT ΔpabA …….P1 transduction
• abgT over-expression plasmid (pJ128) were transformed into
appropriate strains.
8. C. elegans strains used
SS104 glp-4(bn2)
UF208 (WT)
UF209 gc
p-2.1(ok1004)
9. Results
E. coli is required for folic acid supplementation
to prevent a C. elegans folate deficiency
10.
11. Folic acid supports growth of E. coli pabA mutants via
abgT-dependent uptake of PABA-glu
12. Folic acid shortens C. elegans lifespan via AbgT
dependent uptake of PABA-glu
13. Discussion
major route
FOLT-1 in C.elegan
PCFT in small intestine of humans
E. coli PABA-glu transporter(AbgT).
Bacterial gene, and its level of expression both
influence route for folic acid.
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Bacterial route for folic acid in humans
Only study to report PABA &PABA_glu
Reported issues about stability and dissolution
PABA as human faecal excretory product.
studies in rodents and piglets infusion of labelled PABA into
the cecum
Route exist in humans but undetermined importance of route
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The bacterial route increases bioavailability.
bacterial activity/toxicity
several diseases, such as:
inflammatory bowel disease
small intestinal bacterial overgrowth
abgT gene in enteric pathogens including :
Enterobacter cloacae
Salmonella enterica
Staphylococcus aureus