Control of bacterial infections

Question 1

principles of controlling bacteria?

Answer 1

1 - reduce exposure - sanitation
2 - reduce susceptibility - vaccination
3 - chemotherapy - antibiotics

Question 2

first use of antibiotics?

Answer 2

1940s

Question 3

antibiotics that target cell wall? action

Answer 3

beta-lactams eg penicillin and cephalosporins

• bind active site of transpeptidase to irreversibly inhibit peptidoglycan crosslinking causing cell lysis.
• vancomycin blocks access to the transpeptidase

Question 4

how do antibiotic inhibit translation

Answer 4

1- tetracycline binds 30s and prevents binding of amino acyl tRNA
2 - chloramphenicol binds 50s and inhibits peptidyl transferase activity
3 - aminoglycosides (gentamicin, neomycin) alter conformation of 16s rRNA in 30S subunit to inhibit tRNA selection and peptide elongation

Question 5

how do antibiotics inhibit folate synthesis

Answer 5

2 enzymes targeted in the pahtway that generates it for purine and hence DNA synthesis.
1 - dihydropteroate synthase - sulfonamide (compete with the pABA substrate)

2 - dihydrofolate reductase - trimethoprim (binds and inhibits it)

Question 6

how do antibiotics inhibit nucleic acid synthesis?

Answer 6

1 - fluroquinolones (ciprofloxacin) inhibit gyrase and topoisomerase used to control DNA topology during replication and transcription.
2 - rifampicin complexes with DNA dependent RNAP, blocking transcription

Question 7

a god example of antibiotic resistance?

Answer 7

E coli causing septacaemia and meningitis are becoming increasingly resistant to the fluoroquinolone ciprofloxacin.

Question 8

mechs via which antibio resistance arises

Answer 8

point mutation
acquisition via conugation, transduciton or transformation.
selected for by exposure

Question 9

4 mechs of antibiotic resistance

Answer 9

1 - enzyme mediated inactivation
2 - alteration of target
3 - metabolic by-pass
4 - efflux pumps

Question 10

how do bacteria inactivate antibiotics

Answer 10

with enzymes. eg chloramphenicol by chloramphenicol acetyltransferase
- beta-lactamases cleave penicillins

Question 11

how do bacteria alter a target to confer antiobiotic resistance

Answer 11

mutation so that it no longer binds effectively. eg ribosome mutation for streptomycin resistance.
- alternative penicillin binding proteins in peptidoglycan. inc vancomycin resistance in many gram positive.

Question 12

how do bacteria use metabolic bypass to confer antibiotic resistance

Answer 12

an alternative enzyme for the same pathway to replace that being blocked.
eg plasmid encoded DHFR for folate synthesis that has 1000-fold lower affinity for trimethoprim.

Question 13

how are drug efflux pumps used

Answer 13

determines multidrug resistance eg in gram -ve pseudomonas and E. coli
- tripartite pumps. drugs bind the inner membrane transporter eg an ATPase or proton antiporter, and are ejected into a unique TolC exit duct which spans the periplasm and outer membrane to eject the drug.

Question 14

the 8 principle bacterial vaccines

Answer 14

1 - diphtheria - toxoid. part of diphtheria-pertussis- tetanus triple vaccine
2 - tetanus - toxoid
3 - whooping cough - killed bordatella pertussis
4 - pneumonia - polysaccharide from S.pneumoniae and H.influenzae
5 - meningitis - purified polysaccharide from Neisseria meningitidis. capsular polysaccharide of Haemophilus influenzae B coupled to the tetanus toxoid
6 - typhoid fever - killed salmonella typhi
7 - cholera - killed or crude fraction Vibrio cholerae
8 - tuberculosis - BCG. attenuated strain of Mycobacterium bovis.