RO Lecture 7

Question 1

What is antibiotic resistance

Answer 1

It is when a microbe that was previously susceptible to an antibiotic is no longer affected by it

Question 2

3 ways bacteria can become resistant to antibiotics?

Answer 2

1.Releasing enzymes that can destroy or inactivate the antibiotic.
2.Alteration of Antibiotic Targets.
3.Prevention of Antibiotic Access to Target.

Question 3

Enzymes destroy/inactivate antibiotics in 2 ways:

Answer 3

-Inactivation by hydrolysis
-Inactivation by steric hindrance

Question 4

Example of inactivation by hydrolysis:

Answer 4

-β-lactamases (penicillinase) degrade penicillins and cephalosporins by hydrolysing the β-lactam ring

Question 5

Alteration of Antibiotic targets:

Answer 5

-Changes to the structure of the target (without loss of function) which prevent efficient binding of the antimicrobial agent.
-Caused by DNA alteration or posttranslational modification

Question 6

Examples of Antibiotic targets:

Answer 6

-Single amino-acid change in bacteria ribosomal protein which prevents efficient binding of macrolides.
-Resistance to erythromycin, rifamycin, and antimetabolites has developed by this mechanism

Question 7

Alteration of antibiotic targets: Methicillin-resistant Staphylococcus aureus (MRSA)

Answer 7

Methicillin is resistant to degradation by β-lactamases.

Question 8

Prevention of antibiotic access to targets is achieved by:

Answer 8

-Reduced permeability
-Increased efflux

Question 9

Reduced permeability:

Answer 9

-Is the alteration of pores/channels to prevent antibiotics from crossing the membrane and reaching their targets

Question 10

Increased efflux:

Answer 10

-Overexpression of efflux pumps that actively transport antibiotics out of the bacterial cell.
-Multidrug resistance (MDR) pumps is what causes the resistance

Question 11

Prevention of antibiotic access to target: Examples of antibiotics this method works on

Answer 11

-Tetracyclines
-Quinolones
-Some aminoglycosides

Question 12

Other ways antibiotic resistance occurs:

Answer 12

-Genetic mechanisms
-Resistance plasmids

Question 13

Genetic mechanism:

Answer 13

-Involves genetic changes followed by natural selection
-Antibiotics do not induce mutations but can select for them
-Spontaneous changes to chromosomal DNA: Leads to alteration in amino acid sequence of protein product –can alter target (E.g. ribosomal proteins altered so antibiotic can no longer bind); transferred vertically-Acquisition of plasmids: Extra-chromosomal DNA containing resistance genes can be acquired

Question 13

Genetic mechanism:

Answer 13

-Involves genetic changes followed by natural selection
-Antibiotics do not induce mutations but can select for them
-Spontaneous changes to chromosomal DNA: Leads to alteration in amino acid sequence of protein product –can alter target
-Transferred vertically

Question 14

Resistance plasmids were discovered when?

Answer 14

-Discovered in Shigella, Japan in 1959.

Question 15

2 components of resistance plasmids:

Answer 15

1. Resistance Transfer Factor (RTF) which includes genes required for conjugation
2. Resistance (R) genes/r-determinants: Each R gene contains information that confers resistance to one type of antibiotic or heavy metal (transferred horizontally by conjugation, transformation, or transduction)

Question 16

Mechanism for transformation:

Answer 16

Uptake of naked DNA fragments from one bacteria cell to another in a solution.

Question 17

Mechanism for transduction:

Answer 17

1. Phage injects DNA into bacterial cell.
2. Phage obtains bacterial DNA and then infects a new cell
3. Genes from the first bacterial host are incorporated into chromosome of new host

Question 18

Mechanism for conjugation:

Answer 18

-DNA is transferred from a donor to a recipient bacterium by direct contact.

Question 19

How to minimize the development of antibiotic resistance?

Answer 19

1. Completing courses of antibiotics
   2.Administering two or more drugs simultaneously: Can have a synergistic effect (e.g. different targets)
   3.Restriction of use to essential cases only 4.Use of narrow-spectrum antibiotics (preserve microflora)
   5.Keeping reserve antibiotics

Question 20

Other ways bacteria can survive antibiotic treatment:

Answer 20

-Antibiotic tolerance: A population of bacteria without a resistance mechanism that can survive antibiotic treatment for a longer duration
-Antibiotic persistence: Persisters are a subpopulation of tolerant bacteria found within a susceptible population.

Question 21

Examples of combined antimicrobial therapy:

Answer 21

-Augmentin: Clavulanic acid and amoxicillin are used together because Clavulanic acid contains a β-lactam ring but is not active on its own; inhibits action of βlactamase enzymes and thus protects the activity of amoxicillin