L3 - Antibiotic Resistance

Question 1

What is a key factor in preventing antibiotic resistance?

Answer 1

Key Factor: Patient compliance – finish the full course of antibiotics.

Question 2

What contributes to the overuse of antibiotics?

Answer 2

Contributing Factors:
Inappropriate prophylactic use.
Use in hospital environments (e.g., MRSA).
Animal husbandry practices.
Insufficient supply or poor quality of drugs.

Question 3

What is the importance of combination therapy in preventing resistance?

Answer 3

Importance: Single-use antibiotics, like rifampicin for tuberculosis, should be combined with others to prevent the development of resistance.

Question 4

What environmental factors contribute to antibiotic resistance?

Answer 4

Contributing Factors:
Poor hygiene, especially in hospital settings.
International travel.
Immune-compromised patients and the elderly population.

Question 5

Why do Mycoplasma have natural resistance to cell wall synthesis inhibitors?

Answer 5

Reason: Mycoplasma do not have a cell wall, so they are naturally resistant to antibiotics targeting cell wall synthesis, like Penicillins.

Question 6

Why do Mycobacteria, Chlamydia, and Legionella have natural resistance to certain antibiotics?

Answer 6

Reason: These bacteria are intracellular and naturally resist antibiotics that cannot penetrate human cells, such as Penicillins.

Question 7

Why does Vancomycin have natural resistance in gram-negative bacteria?

Answer 7

Reason: Vancomycin cannot penetrate the outer membrane of gram-negative bacteria, leading to natural resistance in these organisms.

Question 8

Why can’t Metronidazole be used for aerobic bacteria?

Answer 8

Reason: Aerobic bacteria require O2 to survive, but O2 prevents the activation of Metronidazole, making it ineffective for these bacteria.

Question 9

Why can’t Aminoglycosides be used for anaerobic bacteria?

Answer 9

Reason: Aminoglycosides require O2-dependent active transport for uptake, which anaerobic bacteria lack, making the drug ineffective in these environments.

Question 10

What is vertical transmission of resistance?

Answer 10

Vertical transmission: Transfer of resistance through generations via spontaneous mutations that improve survival under selection pressures. This is a Darwinian survival process.

Question 11

What is horizontal transmission of resistance?

Answer 11

Horizontal transmission: Transfer of genetic material between different bacteria, often involving the same strain, but can also involve different strains.

Question 12

What are the methods of horizontal transmission?

Answer 12

Conjugation: Transfer of plasmids via direct cell-to-cell contact.
Transformation: Uptake of free DNA from the environment.
Transduction: Phage-mediated transfer of genetic material.
Vesicle transfer: Transfer via bacterial vesicles.

Question 13

Where is genetic material for resistance stored in bacteria?

Answer 13

Genetic material for resistance is stored on chromosomes or plasmids.

Question 14

What are R-plasmids?

Answer 14

R-plasmids (resistance plasmids) are plasmids that carry multiple resistance genes and can be transferred between bacteria.

Question 15

Can virulence factors be transferred along with resistance?

Answer 15

Yes, virulence factors can also be transferred on R-plasmids or resistance cassettes.

Question 16

What is conjugation in bacterial DNA transfer?

Answer 16

Conjugation is the process where genetic material is transferred between bacteria through direct cell-to-cell contact.

Question 17

How does conjugation occur?

Answer 17

A donor bacterium (usually carrying an F-plasmid) forms a pilus to connect with a recipient bacterium, transferring DNA, such as plasmids, into the recipient.

Question 18

What can be transferred during conjugation?

Answer 18

Plasmids, which may carry resistance genes or virulence factors, can be transferred during conjugation.

Question 19

What do plasmids contain?

Answer 19

Plasmids are small, circular pieces of DNA that can carry virulence factors and resistance genes, and can be transferred between bacteria.

Question 20

What are transposons?

Answer 20

Transposons are small pieces of DNA that can jump in and out of chromosomes through recombination events, transferring genetic material, including resistance or virulence factors, between chromosomes.

Question 21

How do transposons transfer genetic material?

Answer 21

Transposons can move genetic material from one location to another within the same genome or between different genomes, facilitating the spread of genes like antibiotic resistance.

Question 22

What is transformation in DNA transfer?

Answer 22

Transformation is the process where dead cells release genetic material, which is then taken up by nearby cells.

Question 23

How do cells acquire genetic material in transformation?

Answer 23

Nearby cells take up donor DNA from the environment after a cell dies and releases its genetic content.

Question 24

What is transduction in DNA transfer?

Answer 24

Transduction is the process by which bacterial DNA is transferred between bacteria via a bacteriophage (a virus that infects bacteria).

Question 25

How does transduction occur?

Answer 25

A bacteriophage infects a bacterium, mistakenly incorporating host DNA into its viral genome. This virus then infects another bacterium, transferring the donor DNA.

Question 26

What is DNA transfer via vesicles?

Answer 26

DNA transfer via vesicles is a recently discovered mechanism (2017) where resistant plasmids are released in small vesicles by bacteria.

Question 27

How does DNA transfer via vesicles work?

Answer 27

The vesicles containing resistant plasmids are released by the donor bacterium and taken up by a recipient cell, transferring the resistance genes.

Question 28

What is the role of Penicillin binding protein (PBP)?

Answer 28

PBP catalyzes the transpeptidation of the interpeptide bridge in the peptidoglycan layer of bacteria.

Question 29

How do β-lactam antibiotics work?

Answer 29

β-lactam antibiotics covalently bind to a serine in the active site of PBP, blocking its enzymatic activity and disrupting bacterial cell wall synthesis.

Question 30

How do bacteria resist β-lactam antibiotics?

Answer 30

β-lactamase enzymes: Some bacteria express β-lactamases, which cleave and inactivate β-lactam antibiotics.
Penicillin Binding Protein 2a (PBP2a): Some bacteria express a modified PBP2a with an altered active site that does not bind Penicillin.

Question 31

How efficient are β-lactamases?

Answer 31

1 molecule of β-lactamase can inactivate 1000 penicillin molecules per second.

Question 32

Can β-lactamases spread between bacteria?

Answer 32

Yes, β-lactamases can diffuse away from Gram-positive bacteria and protect other bacteria from β-lactam antibiotics.

Question 33

Which bacteria most commonly express β-lactamases?

Answer 33

Staphylococcus aureus is the most common β-lactamase-expressing bacterium.

Question 34

How is β-lactamase expression induced in Staphylococcus aureus?

Answer 34

Chromosomal expression of β-lactamase in Staphylococcus aureus is induced by β-lactam antibiotics, resulting in a 50-80-fold increase in β-lactamase production.

Question 35

Can β-lactamases spread in the environment?

Answer 35

Yes, β-lactamases can leak out of Staphylococcus aureus and protect other bacteria in the environment.

Question 36

How is β-lactamase expression induced in Escherichia coli?

Answer 36

Chromosomal expression of β-lactamase in Escherichia coli is also induced by β-lactam antibiotics.

Question 37

Can Escherichia coli acquire β-lactamase resistance from other bacteria?

Answer 37

Yes, Escherichia coli can acquire β-lactamase genes on R-plasmids, resulting in constitutive expression of β-lactamase.

Question 38

Why can’t β-lactamase leak out of Gram-negative bacteria?

Answer 38

Gram-negative bacteria, like Escherichia coli, have an outer membrane that prevents the leakage of β-lactamase into the environment.

Question 39

How do β-lactamases protect other bacteria?

Answer 39

β-lactamases can diffuse out of bacteria (e.g., from Gram-positive bacteria) and protect other bacteria from β-lactam antibiotics.

Question 40

What is Amoxiclav?

Answer 40

Amoxiclav is a combination of amoxicillin (a β-lactam antibiotic) and clavulanic acid (a β-lactamase inhibitor).

Question 41

Do β-lactamase inhibitors have antibacterial activity?

Answer 41

No, β-lactamase inhibitors, such as clavulanic acid, do not have antibacterial activity.

Question 42

How do β-lactamase inhibitors work?

Answer 42

β-lactamase inhibitors covalently bind to and inactivate β-lactamase enzymes, preventing them from breaking down β-lactam antibiotics.

Question 43

Is the combination of β-lactam and β-lactamase inhibitor synergistic?

Answer 43

No, the combination of β-lactam antibiotics and β-lactamase inhibitors is not considered synergism because the inhibitors do not directly contribute to antibacterial activity. They simply prevent the antibiotic from being inactivated.

Question 44

What is the mechanism behind methicillin resistance in Staphylococcus aureus (MRSA)?

Answer 44

MRSA expresses an additional molecule, PBP2, which performs the same function as Penicillin Binding Protein (PBP) but is insensitive to methicillin.

Question 45

How does MRSA resist the effects of methicillin?

Answer 45

MRSA does not mutate the original PBP gene but instead expresses PBP2, a modified version of the target enzyme that does not bind to methicillin, rendering the antibiotic ineffective.

Question 46

What is reduced drug accumulation in bacteria?

Answer 46

Reduced drug accumulation occurs when bacteria limit the amount of drug that enters the cell, preventing the drug from reaching effective concentrations.

Question 47

How do bacteria reduce drug penetration?

Answer 47

Increased lipopolysaccharide (LPS) expression on the outer membrane can block the drug from entering the cell.
Downregulation of porin expression reduces the entry of drugs that rely on porins for penetration.
Some bacteria also have an extra mucus layer that further limits drug entry.

Question 48

How do bacteria reduce drug accumulation through efflux pumps?

Answer 48

Bacteria can upregulate efflux pumps, which actively transport drugs out of the cell, reducing their intracellular concentration.

Question 49

How do efflux pumps get activated?

Answer 49

Tet response element: When tetracycline (Tet) or similar drugs are sensed, the bacterium binds the Tet response element in the promoter region of the pump gene.
This binding acts as a transcription factor, turning on the expression of the efflux pump.

Question 50

How can drug design help overcome efflux pumps?

Answer 50

Designing drugs to inhibit efflux pump activity can prevent the drug from being pumped out, ensuring the drug remains effective inside the bacterial cell.

Question 51

What induces the expression of efflux pumps in bacteria?

Answer 51

The antibiotic itself can induce the expression of efflux pumps in bacteria.

Question 52

How does tetracycline activate the efflux pump?

Answer 52

Tetracycline binds to the Tet response element in the promoter of the pump gene, activating the pump’s expression.

Question 53

Which antibiotics are affected by efflux pumps in Staphylococcus aureus?

Answer 53

Staphylococcus aureus has efflux pumps that eject macrolides (e.g., erythromycin) and fluoroquinolones.

Question 54

How can you counteract the action of efflux pumps?

Answer 54

You can develop efflux pump inhibitors to prevent the pumps from removing the antibiotic, thus increasing the drug’s effectiveness.

Question 55

What is quorum sensing in bacteria?

Answer 55

Quorum sensing is a form of bacterial cell communication where bacteria coordinate their behavior based on population density.

Question 56

What does quorum sensing control in bacteria?

Answer 56

Quorum sensing regulates the expression of virulence factors and antibiotic resistance factors in bacteria.

Question 57

How does quorum sensing affect antibiotic treatment?

Answer 57

It makes it harder for antibiotics to penetrate bacterial structures, such as biofilms in catheters, artificial heart valves, and dental plaque.

Question 58

What does “quorum” refer to in bacterial quorum sensing?

Answer 58

Quorum refers to the minimum number of bacteria that must be present to make the bacterial assembly “valid” for communication and action.

Question 59

What happens when quorum is formed in bacteria?

Answer 59

Once quorum is formed, bacteria attach to surfaces and multiply.

Question 60

How do bacteria sense quorum?

Answer 60

Bacteria sense the number of other bacteria around them by using chemical messengers that increase when enough bacteria are present.

Question 61

How does quorum sensing affect bacterial behavior?

Answer 61

Once enough bacteria have gathered, the expression of virulence factors and resistance factors is increased, enhancing their ability to infect and resist antibiotics.

Question 62

How could antibiotics be used to counteract quorum sensing?

Answer 62

Instead of using antibiotics to kill bacteria directly, a strategy could involve preventing quorums from forming, disrupting bacterial communication.