INF1 - F. FOLATE AND UTIS-COVERED

Question 1

what is the main causative organism of UTIs

Answer 1

Escherichia coli

Question 2

why are UTIs more common in women

Answer 2

• shorter urethra
• location closer to anus
• easier for E.coli which dwells in intestines to enter and cause infection

Question 3

what is infection of the lower urinary tract (bladder) called

Answer 3

cystitis

Question 4

what is infection of the lower urinary tract (urethra) called

Answer 4

urethritis

Question 5

symptoms of a lower UTI

Answer 5

painful/burning urination (dysuria)
frequent urination (at night - nocturia) or
urge to urinate (or both)
cloudy urine

Question 6

what is infection of the upper urinary tract (kidneys) called

Answer 6

pyelonephritis

Question 7

symptoms of a upper UTI

Answer 7

fever
lower back pain/loin pain (kidneys)
lower UTI symptoms aswell

serious:
haematuria

Question 8

structure of E. coli

Answer 8

• gram -ve
• coliform
• rod shaped enteric bacteria
• forms part of microbiome of mammalian GIT

Question 9

how does E. coli cause UTIs

Answer 9

entry from intestinal tract to urinary tract

Question 10

how does E. coli cause gastroenteritis

Answer 10

eating infected food contaminated with pathogenic strains

Question 11

what 3 antigens on E. coli cause pathogenicity

Answer 11

Polysaccharide shell
O-polysaccharide
lipid A - (causes toxic shock)

Question 12

virulence factors of E. coli

Answer 12

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

Question 13

treatment for lower UTI

Answer 13

oral nitrofurantoin (used to be trimethoprim)
3 days
male/pregnant - 7 days

Question 14

treatment for upper UTI

Answer 14

cefalexin

Question 15

what is folate

Answer 15

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)

Question 16

how is folate synthesised in bacteria

Answer 16

• 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

Question 17

how is THF used

Answer 17

as carrier single carbon fragment, used to synthesise adenine, guanine, thymine and methionine for DNA synthesis

Question 18

what is the difference between folate utilisation in bacteria and mammalian cells

Answer 18

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)

Question 19

how do sulphonamides work

Answer 19

• 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

Question 20

how does trimethoprim work

Answer 20

• 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

Question 21

why does resistance to trimethoprim occur

Answer 21

• 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