AB2, L60: Antimicrobial Resistance - NEEDS TO BE EDITED

Given definition, answer w/ term

More toxic; more expensive; less effective

Scale of the Challenge Anti-Microbial Resistance Pose to Humans:

• Heath care providers are forced to use antibiotics that:

  • May be _______ (less/more) toxic

  • Frequently _______ (less/more) expensive

  • _______ (less/more) effective

Higher mortality rates; longer hospital stays; longterm disability

Scale of the Challenge Anti-Microbial Resistance Pose to Humans:

• Patients with resistant infections have _______ (lower/higher) mortality rates

• Survivors have significantly _______ (shorter/longer) hospital stays, delayed recuperation, and _______ (short term/longterm) disability

2050

Scale of the Challenge Anti-Microbial Resistance Pose to Humans:

• Antimicrobial resistance is currently responsible for 1.14 million deaths/year globally since 1990

• Unchecked economic burden of AMR may triple by _______ (year), and bring ~30 million people into extreme poverty

Extensive use

Drivers of Anti-Microbial Resistance:

• What is the major driver of antibiotic resistance?

Scale of the Challenge Anti-Microbial Resistance Pose to Animals:

• 80% of the antibiotics sold in the US were used on farms

• Although Europe has regulations preventing antibiotic use for growth promotion, many farmers are still able to blanket treatment their stock on the basis of ‘treatment’ for diarrhea and respiratory issues

Scale of the Challenge Anti-Microbial Resistance Pose to Animals:

• Antibiotic administration routes to farm animals are varied:

  • Majority delivered via feed/water

  • Intramammary

  • Oral neonatal doses

  • Footbaths

  • Long acting injectables

Horizontal gene transfer

Bacterial Antibiotic Resistance:

• Definition: Gene movement between cells that are NOT direct descendents, can be categorized as either conjugation, transformation, or transduction

• Speed: Fast

• Example: Bacteria A picks up plasmid from Bacteria B that codes for a penicillinase (enzyme that destroys penicillin)

Conjugation

1 of the 3 Types of Horizontal Gene Transfer:

• On Diagram: B

Transformation

1 of the 3 Types of Horizontal Gene Transfer:

• On Diagram: C

• Definition: Genetic transfer process by which free DNA is incorporated into a recipient cell and brings about genetic change

Transduction

1 of the 3 Types of Horizontal Gene Transfer:

• On Diagram: A

• Definition: Bacteria C is filled with bacterial or bacteria infected by viral DNA that has gone from Bacteria A to Bacteria B; rare

Antimicrobial resistance

Efflux pumps

Mechanisms of Antibiotic Resistance:

• Definition: Transport proteins located on the cytoplasmic membrane of bacteria that can expel a wide variety of structurally diverse antibiotics across the membrane and out of the bacteria

Reduced penetration of drug

Mechanisms of Antibiotic Resistance:

• Definition: Decrease uptake of antibiotic

• Example:

  • LPS in Gram negative bacteria provide a barrier to some antimicrobial agents

  • High lipid content in Mycobacterial cell wall makes it difficult for hydrophilic drugs to enter cell

  • Staphylococcus aureus produces a thicker cell wall, making it difficult for vancomycin to enter

Antibiotic cleavage

Mechanisms of Antibiotic Resistance:

• Definition: Bacteria releases enzymes that destroy antibiotic

Antibiotic modification

Mechanisms of Antibiotic Resistance:

• Definition: Release enzymes that add functional groups to antibiotic

• Example:

  • Gram positive bacteria alter the structure/number of penicillin binding proteins. This directly impacts the amount of drug that can bind to its target

Penicillin binding proteins

• Definition: Transpeptidases involved in the construction of peptidoglycan in the cell wall

Multi-Drug Resistance: Next Steps

According to the Jim O’Neill Report:

1. Reduces the use of available microbials

2. Stimulate the development of new antimicrobials

3. Some key antibiotics should not be used in agriculture at all

Multi-Drug Resistance: Next Steps

According to the WHO Action Plan

1. Improve awareness and understanding of AMR

2. To strengthen knowledge and evidence base through surveillance

3. To reduce the incidence of infection through effective sanitation & hygiene

4. To optimize the use of antimicrobial medicines in human and animal health

5. To develop the economic case for new medicines, diagnostics, and vaccines