INF1 - F. FOLATE AND UTIS-COVERED Flashcards
what is the main causative organism of UTIs
Escherichia coli
why are UTIs more common in women
- shorter urethra
- location closer to anus
- easier for E.coli which dwells in intestines to enter and cause infection
what is infection of the lower urinary tract (bladder) called
cystitis
what is infection of the lower urinary tract (urethra) called
urethritis
symptoms of a lower UTI
painful/burning urination (dysuria)
frequent urination (at night - nocturia) or
urge to urinate (or both)
cloudy urine
what is infection of the upper urinary tract (kidneys) called
pyelonephritis
symptoms of a upper UTI
fever
lower back pain/loin pain (kidneys)
lower UTI symptoms aswell
serious:
haematuria
structure of E. coli
- gram -ve
- coliform
- rod shaped enteric bacteria
- forms part of microbiome of mammalian GIT
how does E. coli cause UTIs
entry from intestinal tract to urinary tract
how does E. coli cause gastroenteritis
eating infected food contaminated with pathogenic strains
what 3 antigens on E. coli cause pathogenicity
Polysaccharide shell
O-polysaccharide
lipid A - (causes toxic shock)
virulence factors of E. coli
outer capsule
- protect from phagocytosis
fimbriae and adhesins
- attach to epithelial cells
exotoxins
iron-binding proteins (siderophores)
- acquire iron needed for growth
haemolysins
- release iron from blood cells
type 3 secretion system
- builds an insertion ‘needle’ to inject protein into host cells
treatment for lower UTI
oral nitrofurantoin (used to be trimethoprim)
3 days
male/pregnant - 7 days
treatment for upper UTI
cefalexin
what is folate
aka folic acid and vitamin B9 - co-factor in all living cells
not biology active itself - important molecules when metabolised
mammals - important during rapid cell division ie - infancy and pregnancy (pregnant women given high dose of folic acid)
how is folate synthesised in bacteria
- synthesis of dihydropteroic acid from 1x pteridine and 1x PABA
- glutamic acid added to form dihydrofolic acid
- reduced to tetrahydrofolate by DHFR
THF converted back to DHF so reaction repeats
how is THF used
as carrier single carbon fragment, used to synthesise adenine, guanine, thymine and methionine for DNA synthesis
what is the difference between folate utilisation in bacteria and mammalian cells
bacteria (and protozoa) can’t take up exogenous folate, so they synthesise it
mammalian cells don’t synthesise dihydrofolate so they take it up in the diet and convert to THF in liver
(DHFR different to bacterial one)
how do sulphonamides work
- structural analogues of PABA
- inhibit incorporation of PABA into dihydrophteroic acid
- use decreased due to bacterial resistance
Sulfamethoxazole - can be administered with trimethoprim as exhibit synergistic activity
(co-trimoxazole - not for UTIs, used for prophylaxis of fungal infections, use with high dose corticosteroids or antivirals)
Sulfadiazine
how does trimethoprim work
- selective inhibitor of bacterial DHFR
- structural analogue of the dihydropteroic acid part of DHF (pteridine bit)
- fits into active site of DHFR, strong H bonds formed with amino acid residues and water molecules lining the sure
- can be used for UTIs and rest tract infections and others
why does resistance to trimethoprim occur
- over-production of DHFR by bacteria
- acquisition over gene encoding a resistant form of the enzyme (DHFR TYPE 1, 2 or 5 amongst enterobacteria) so no affinity of DHFR to trimethoprim
Therefore only used where there is a low risk of resistance
Nitrofurantoin is first line for UTIs
