Antibiotic Resistance

Question 1

In 1956, 70% of staphylococcus aureus were resitant to PenG, how?

Answer 1

Aquisition of the gene for beta lactamase enzyme

Question 2

What is methicillin?

Answer 2

Modified lactamase-resistant penicillin

Question 3

What is MRSA?

Answer 3

methicillin resistant Staph Aureus

Question 4

If MRSA were to live with other bacteria that are resistant naturally to other drugs such as vancomycin, what would happen?

Answer 4

Due to the exchange of genetic info between bacteria, there may be the development of vancomycin-resistant MRSA

Question 5

What antibiotic do we normally give to treat MRSA?

Answer 5

Vancomycin

Question 6

Name 6 mechanisms that bacteria can become resistant to antibiotics

Answer 6

• Drug inactivation (like with beta lactamase)
• Alter target or aquire new target of the antibiotic (e.g. mutated RNA pol means that antibiotics can’t bind to it any more)
• Overproduction of target
• Intrinsic impermeability
• Efflux pump (new or increased action of efflux pump)
• Metabolic by-pass

Question 7

Describe one way which MRSA become penicillin resistant

Answer 7

MRSA aquired a whole new gene for a new target for the binding of all of the penicillins

Question 8

Describe how trimethoprin resistance by target overproduction can happen

Answer 8

Timethoprin inhibits the second enzyme in the folic acid pathway but bacteria can become resistant by overproducing the precursor to outcompete trimethoprin

Question 9

Describe the mechanism of vancomyocin resistance

Answer 9

• Vancomyocin usually binds to the peptidoglycan terminus D-ala-D-ala
• A new bacterial metabolic pathway causes a new terminus D-ala-D-lac
• So less vancomyocin binding
• So less disruption to peptidoglycan cross linking

Question 10

Describe what natural antibiotic resistance is as opposed to aquired

Answer 10

Innate resistance is normally expressed by virtually all strains of a particular bacterial species.

Acquired resistance is gained by previously susceptible bacteria either through mutation or horizontally obtained from other bacteria possessing such resistance via transformation, transduction, or conjugation.

Question 11

Describe the 2 genetic mechanisms involved in the transfer of bacterial antibiotic resistance

Answer 11

• Chromosome mediated
• Plasmid mediated gene exchange

Question 12

What are non-genetic mechanisms in bacterial antibiotic resistance?

Answer 12

tolerance

Question 13

Which type (gram) of bacteria is plasmid-mediated gene exchange more common?

Answer 13

gram negative

• transferred by conjugation
• multi-drug resistance

Question 14

Name the 3 methods of gene transfer in bacteria

Answer 14

• Transformation
• Transduction
• Conjugation

Question 15

Describe what bacterial transformation is

Answer 15

The take up of DNA fragments from the environment (like from dead organisms) this gene may carry virulence, drug resistance etc.

Question 16

Describe what bacterial transduction is

Answer 16

This is via bacteriophage, can be very rapid through populations of bacteria

Question 17

Describe what bacterial conjugation is

Answer 17

Bacteria come together and form a conjugal tranfer tube/structure to receieve DNA from one donor bacterium to a recipient bcterium

• conjugal tube may be encoded by a plasmid

Question 18

What two agents do we have in co-amoxiclav?

Answer 18

Clavulanic acid binds to beta lactamase

• It has a very similar structure to penicillin with the beta lactam ring on the right

Question 19

HOW do beta lactams cause disruption of the cell wall?

Answer 19

Bind to PBPs in the cytoplasmic membrane - these target proteins catalyze the synthesis of peptidoglycan (forms the cell wall)

• interfere with cross linking

Question 20

Describe 3 ways that beta-lactam resistance can occur in gram -ve bacteria

Answer 20

• outer membrane porin mutation
• penicillin binding protein mutation
• beta lactamase enzyme is aquired

Question 21

How does vancomycin resistance come around? And explain how vancomycin would normally work

Answer 21

Terminal D-ala-D-ala is changed to D-ala-D-lactate which prevents vancomycin from binding to inhibit crosslinking.

• aquisition of the van operon allows for a new metabolic pathway to produce the lac version

Question 22

Describe 2 non-genetic mechanisms to become resistant to antibiotics

Answer 22

• Inaccessibility to the drugs
• Stationary phase (a phase of growth in vivo) may cause biofilms/vegetations

Question 23

How can the production of biofilms cause a resistance to certain antibiotics - this is a non-genetic antibiotic resistance

Answer 23

Biofilms are NOT susceptible to inhibitors of cell wall synthesis as they are not using those enzymes anyway - so we have to use other antibiotics

Question 24

Describe some ways that we can prevent/overcome antibiotic resistance

Answer 24

Question 25

Example of how we have had to constantly change our drugs/treatments due to antibiotic resistance in Neisseria gonorrhoeae

Answer 25

Question 26

What are CREs?

Answer 26

carbapenems resistant enterobacteriaceae

Question 27

How have CREs come about?

Answer 27

Aquired the new gene ndm 1 which destroys antibiotics (metalloprotease)

Question 28

What is horizontal transmission?

Answer 28

In general, transmission of viruses can occur through two pathways: horizontal and vertical transmission.

In horizontal transmission, viruses are transmitted among individuals of the same generation, while vertical transmission occurs from mothers to their offspring.

Question 29

What is antibiotic stewardship and why is it important?

Answer 29

Antibiotic stewardship is the effort to measure and improve how antibiotics are prescribed by clinicians and used by patients.

Improving antibiotic prescribing and use is critical to effectively treat infections, protect patients from harms caused by unnecessary antibiotic use, and combat antibiotic resistance.