Control of bacterial infections

Question 1

What are the three main principles of bacterial disease control?

Answer 1

1. Reduce exposure by disinfection
2. Reduce susceptibility of individuals to infection
3. Chemotherapy treatment

Question 2

How does resistance to antibiotics arise?

Answer 2

1. Point mutations in chromosomal genes
2. Acquisition of new genes by conjugation, transduction or transformation
3. Natural selection by exposure to antibiotics

Question 3

What are the biochemical mechanisms of antibiotic-resistance?

Answer 3

1. Enzymatic inactivation
2. Alteration of target
3. Metabolic bypass
4. Increased drug efflux

Question 4

How does penicillin work?

Answer 4

1. Mimics D-ala-D-ala peptidoglycan cross-link
2. Binds to active site of transpeptidase
3. Irreversibly inhibits peptidoglycan cross-linking
4. Causes cell lysis

Question 5

How are bacteria resistant to penicillin?

Answer 5

β-lactamases cleave penicillins

Question 6

How does chloramphenicol work?

Answer 6

Binds to 50S subunit of ribosome and inhibits peptidyl transferase activity

Question 7

How do aminoglycosides work?

Answer 7

Alter conformation of 16S rRNA in 30S subunit

Inhibit tRNA selection and elongation of protein

Question 8

How are bacteria resistant to aminoglycosides and chloramphenicol?

Answer 8

Produce acetyl transferases that modify drugs to prevent binding to ribosomes

Question 9

How does tetracycline work?

Answer 9

Binds 30S ribosome subunit and prevents binding of aminoacyl tRNA

Question 10

How are bacteria resistant to tetracycline?

Answer 10

Produce ribosomal protection proteins that have structural similarity to translation elongation factors

Dislodge tetracycline from ribosome

Question 11

How do fluoroquinolones work?

Answer 11

Block synthesis of nucleic acids by inhibiting gyrase and topoisomerase

Question 12

How are bacteria resistant to fluoroquinolones?

Answer 12

Qnr binds topoisomerase to hysically block binding of drug

Question 13

How does vancomycin work?

Answer 13

Binds D-ala-D-ala and blocks access to transpeptidase, prevents peptidoglycan cross-links

Question 14

How are bacteria resistant to vancomycin?

Answer 14

Produce different peptidoglycan biosynthetic enzymes that form D-ala-D-lac cross-links instead

Question 15

How do sulfonamides work?

Answer 15

Compete with pABA for binding to enzyme dihydropteroate synthase

Inhibits folic acid synthesis

Question 16

How does trimethoprim work?

Answer 16

Inhibits dihydrofolate reductase

Inhibits folic acid synthesis

Question 17

How are bacteria resistant to sulfonamides and trimethoprim?

Answer 17

R-plasmid encodes new enzymes, which have a much lower affinity for antibiotics than bacterial versions

Question 18

What determines multi-drug resistance?

Answer 18

Efflux pumps

Question 19

What is the structure of efflux pumps?

Answer 19

Tripartite

1. Inner membrane transporter
2. ATPase or proton antiporter
3. TolC exit duct spanning periplasm and outer membrane