BS1040 Topic 4 Lecture 3 Antimicrobial resistance

What is antimicrobial resistance (AMR)?

The ability of microorganisms (bacteria, viruses, fungi, parasites) to change over time so they no longer respond to medicines, making infections harder to treat.

Who defines AMR as the failure of medicines to control or kill microorganisms?

The World Health Organization (WHO).

What are antimicrobials?

Compounds that stop or slow the growth of microorganisms, including antibiotics, antifungal, antiparasitic, and antiviral drugs.

Which type of antimicrobial is the focus of this lecture?

Antibiotics, which specifically target bacteria.

What are resistant microorganisms?

Microbes that are no longer controlled or killed by an antimicrobial.

What were treatment options like before antibiotics?

Non-specific and often toxic treatments, such as heavy metals like mercury for syphilis or gonorrhoea.

What was the first antibiotic discovered?

Pyocyanase in the 1890s by Rudolf Emmerich and Oscar Löw.

How was pyocyanase discovered?

Extracted from infected bandages containing Pseudomonas aeruginosa.

Who discovered penicillin and when?

Alexander Fleming in 1928.

Why was penicillin revolutionary?

It targeted bacteria with low toxicity to humans, transforming medicine and reducing infection mortality.

What was the "Golden Age" of antibiotic discovery?

1940s to 1960s.

What major problem has emerged since the 1990s regarding antibiotics?

Few new antibiotic classes have been introduced, increasing concern about resistance.

How many new classes of antibiotics were introduced between 1990 and 2020?

Very few - almost none that were truly novel.

What are some factors contributing to limited new antibiotic discovery?

Scientific difficulty, high development cost, low profitability, and overuse of existing drugs.

How do antibiotics work?

They target specific bacterial structures or functions essential for survival.

What are the main bacterial targets of antibiotics?

Cell wall synthesis, protein synthesis, nucleic acid synthesis, and metabolic pathways.

What is meant by "spectrum of activity"?

The range of bacteria an antibiotic is effective against—broad or narrow spectrum.

When is a broad-spectrum antibiotic advantageous?

When the infecting bacterium is unknown or when multiple bacterial types are involved.

Why don't antibiotics harm human cells?

Because they target bacterial structures absent in human cells, like peptidoglycan cell walls or bacterial ribosomes.

What are the four main mechanisms of antibiotic resistance?

LIMIT - reduce uptake; REMOVE - pump antibiotic out; ATTACK - destroy antibiotic; AVOID - modify target.

What does "LIMIT" mean in antibiotic resistance?

Reducing permeability or preventing uptake of the antibiotic.

What does "REMOVE" mean in antibiotic resistance?

Efflux pumps actively export antibiotics from the bacterial cell.

What does "ATTACK" mean in antibiotic resistance?

Enzymes destroy or inactivate the antibiotic (e.g., β-lactamases).

What does "AVOID" mean in antibiotic resistance?

Alteration of the antibiotic target site, reducing binding or effectiveness.

How do bacteria become resistant?

Through inherited mutations or horizontal gene transfer via mobile genetic elements.

What are mobile genetic elements?

Plasmids, transposons, and integrons that carry resistance genes and move between bacteria.

What is spontaneous mutation in this context?

Random genetic change that alters target sites or expression levels, conferring resistance.

What is horizontal gene transfer (HGT)?

Exchange of genetic material between bacteria by conjugation, transformation, or transduction.

What does the theory of selection explain?

Antibiotic use provides selective pressure that favors survival of resistant bacteria.

What happens when antibiotics are used excessively?

Susceptible bacteria die, resistant strains survive and multiply, spreading resistance.

How does globalisation impact AMR?

Facilitates worldwide spread of resistant strains through travel, trade, and migration.

Why is uncontrolled antibiotic use a problem?

It increases selective pressure, accelerating the emergence and spread of resistance.

Where are antibiotics often misused outside of medicine?

In agriculture and animal husbandry to promote growth or prevent disease.

What are potential outcomes of widespread AMR?

Return to a "dark age" of medicine where common infections become untreatable; more pandemics and deaths.

What can be done to combat AMR?

Develop alternative or modified treatments, enforce antibiotic stewardship, and reduce misuse.

What is antibiotic stewardship?

The coordinated effort to use antibiotics responsibly to slow resistance development.

What are some alternative treatments under investigation?

Bacteriophage therapy, antimicrobial peptides, probiotics, and synthetic biology approaches.