Antimicrobial Resistance

What do antibiotics do?

They kill or inhibit the growth of bacteria.

What is selective toxicity?

The ability of antibiotics to kill microbes without damaging the host.

Why isn’t any single antibiotic effective against all microbes?

Because different microbes have varied structures and resistance mechanisms.

What is the difference between antibiotics and antimicrobials?

Antibiotics target bacteria specifically, while antimicrobials target a broader range of microbes.

What is antimicrobial resistance (AMR)?

Resistance of microorganisms to an antimicrobial agent to which they were previously sensitive.

How does AMR typically develop?

Through mutation or acquisition of resistance genes.

What is selective pressure in AMR?

The process by which microbes either adapt or die under antimicrobial use.

What is the consequence of misuse of antimicrobials?

Amplification of antimicrobial resistance.

What is enzymatic inhibition in resistance?

Inactivation of antibiotics by bacterial enzymes such as β-lactamases.

Name one common resistance enzyme.

β-lactamase.

What is the function of β-lactamase?

It splits the amide bond of the β-lactam ring, inactivating the antibiotic.

Where are β-lactamase genes often located?

On plasmids, transposons, or integrons.

What factors affect β-lactamase efficiency?

Hydrolysis rate, affinity for antibiotic, quantity produced, PBP susceptibility, and diffusion rate.

What are aminoglycoside-modifying enzymes?

Enzymes that chemically modify aminoglycosides through acetylation, nucleotidylation, or phosphorylation.

What is decreased permeability in resistance?

A structural barrier in Gram-negative bacteria that blocks antibiotic entry.

How does the LPS layer affect permeability?

It blocks hydrophobic antibiotics like erythromycin.

What are porins?

Proteins that form channels in bacterial membranes for molecule diffusion.

How does porin loss lead to resistance?

Loss of specific porins (e.g., OprD) reduces antibiotic uptake.

What is efflux in antimicrobial resistance?

The active pumping out of antibiotics by the bacterial cell.

Name a transporter system in efflux mechanisms.

NorA or Bmr transporters in Gram-positive bacteria.

What are the efflux pump groups in Gram-negatives?

MF (major facilitator) and RND (resistance-nodulation-division) groups.

What gene confers tetracycline efflux resistance?

Tet gene.

What efflux genes are found in macrolide resistance?

mef, msr, and mreA.

What is the altered target site mechanism?

Modification of antibiotic target sites, reducing binding and efficacy.

Which ribosomal changes affect macrolides?

Methylation of ribosomal RNA by erm genes.

What is the effect of 16S rRNA methylation?

It prevents aminoglycoside binding, causing high-level resistance.

What are the vancomycin resistance genes?

VanA, VanB, VanD (D-lactate substitution); VanE, VanG (D-serine substitution).

What does the mecA gene encode?

PBP2a, a penicillin-binding protein with low affinity for β-lactams.

What resistance does mecA confer?

Methicillin resistance (e.g., MRSA).

What is SCCmec?

Staphylococcal cassette chromosome carrying mecA.

How do quinolones develop resistance?

Through point mutations in the gyrase A subunit QRDR region.

What are sul1 and sul2 genes associated with?

Sulfonamide resistance via altered dihydropteroate synthase.

What does the tetM gene do?

Protects ribosomes from tetracycline inhibition.

How does quinolone protection work?

Prevents DNA gyrase from binding quinolones.

What is target overproduction?

Excess production of antibiotic targets, outcompeting the drug’s action.

How does knowing resistance mechanisms help therapy?

Helps in choosing synergistic drug combinations.

Give an example of a synergistic drug combo.

Sulfamethoxazole + trimethoprim.

Another example of a synergistic combo?

β-lactam + β-lactamase inhibitor (e.g., amoxicillin + clavulanate).

Why combine aminoglycosides and β-lactams?

β-lactams disrupt the wall, aiding aminoglycoside entry and action.

What is one consequence of AMR?

Treatment failures leading to patient deaths.

How does AMR affect medical procedures?

It jeopardizes life-saving surgeries and treatments.

What is a societal impact of AMR?

Increased healthcare costs and burden.

How can antibiotic use in one person affect others?

It can contribute to community-wide resistance.

What are some high-risk effects of AMR?

Increased morbidity, mortality, prolonged illness.

Why are immunocompromised patients more vulnerable?

They have weaker defenses and limited treatment options.

What practices promote AMR?

Indiscriminate drug use, poor hygiene, OTC misuse, livestock antibiotics.

How does pollution contribute to AMR?

Pharmaceutical waste in water promotes environmental resistance genes.

What makes a resistance mechanism particularly dangerous in bacteria?

The presence of multiple resistance mechanisms in a single organism.

How do bacteria acquire β-lactamase genes?

Through chromosomal mutations, plasmids, transposons, or integrons.

What does the suffix in β-lactamases (e.g., AAC(3′)) indicate?

The type of enzymatic activity and the molecular site of modification.

Why are hydrophobic antibiotics less effective against Gram-negatives?

The LPS outer membrane restricts their entry.

What is OprD and why is it important in resistance?

A porin protein in Pseudomonas aeruginosa; its loss contributes to imipenem resistance.

What happens when an antibiotic is pumped out by efflux?

Its intracellular concentration is too low to exert an effect.

What group do most tetracycline efflux resistance genes belong to?

Major Facilitator (MF) family in Gram-negatives.

What does the erm gene encode?

A methyltransferase that modifies 23S rRNA in the 50S subunit.

How do bacteria resist glycopeptides like vancomycin?

By altering the terminal D-Ala-D-Ala sequence in their peptidoglycan precursors.

What is the difference between VanA and VanE genes?

VanA replaces D-Ala-D-Ala with D-Ala-D-Lactate; VanE with D-Ala-D-Serine.

What is the function of PBP2a in MRSA?

It has low affinity for β-lactam antibiotics, allowing cell wall synthesis despite treatment.

What does QRDR stand for?

Quinolone Resistance-Determining Region.

How do sul1 and sul2 genes confer resistance?

They produce modified dihydropteroate synthase enzymes not inhibited by sulfonamides.

How does the tetM gene aid tetracycline resistance?

By mimicking elongation factors and displacing tetracycline from the ribosome.

What is one non-genetic method bacteria use to survive antibiotics?

Overproduction of the drug target to saturate the antibiotic.

Why is it dangerous that antibiotics affect people beyond the patient?

Resistant strains can spread and reduce treatment options for others.

What is meant by “therapeutic options are limited”?

Fewer effective drugs remain available to treat resistant infections.

How does poor food-handling promote AMR?

It facilitates the transmission of resistant organisms via contamination.

Why is AMR a problem in livestock farming?

Antibiotics used in animals can select for resistant bacteria transferable to humans.

Why is environmental contamination significant for AMR?

It creates reservoirs of resistance genes that can re-enter human pathogens.

What is the key message in conclusion?

Understanding AMR mechanisms is critical to controlling its spread.