Infectious Diseases Lecture 3: Multidrug Resistance in Bacteria

What are the drugs that kill and stop the growth of bacteria?

Antibiotics

Do antibiotics affect pathogenic or non pathogenic bacteria?

Both

Do antibiotics inhibit eukaryotes?

No

What are the three main classes of antibiotics based on function?

1. Cell wall synthesis

2. Nucleic acid synthesus

3. Protein synthesis

What are the two main types of antibiotics that inhibit cell wall synthesis?

1. Beta lactams

2. Vancomycin

What type of bacteria is vancomycin used for?

Gram positive

What are the three aspects of nucleic acid synthesis that can be affected by antibiotics?

1. Folate synthesis

2. DNA replication

3. RNA transcription

What type of antibiotics affect folate synthesis?

Sulfur drugs

What are the two aspects of protein synthesis that can be affected by antibiotics?

1. 30S subunit

2. 50S subunit

What is the distinctive feature of gram-positive bacteria?

Thick peptidoglycan layer

What is the distinctive feature of gram-negative bacteria?

Outer membrane

What is the cell membrane synthesis affecting antibiotic that only works with gram-negative bacteria?

Polymyxins

What will be the most significant cause of death in the future?

Antibiotic resistance

How does overuse of antibiotics lead to resistance in bacteria?

Adaptive changes in bacterial DNA

What are the two main bacterial lifestyle factors that cause antibiotic resistance?

1. Biofilm

2. Small colony variants (SCV)

What are the two ways biofilms promote antibiotic resistance?

1. Reduce antibiotic penetration

2. Slow growing cells

What do all bacteria require to make nucleotides?

Folate synthesis

How do bacteria make folate since it cannot absorb it from the environment?

De novo

Why are Enterococci intrinsically resistant to folate synthesis antibiotics?

Can absorb folate

What is the main drive of adaptive antibiotic resistance?

Mutation

What is the main drive of acquired antibiotic resistance?

Horizontal gene transfer

What are the three methods of horizontal gene transfer in bacteria?

1. Transformation

2. Transduction

3. Conjugation

What resistance was acquired by S. aureus from enterococcus?

Vancomycin resistance

Which transposon element is the vancomycin resistance present on?

Tn1546

What are the five molecular mechanisms for antibiotic resistance?

1. Transporters

2. Inhibition of uptake

3. Degradation

4. Target modification

5. Antibiotic modification

What is the antibiotic resistance mechanism for beta lactams for gram positive bacteria?

Beta lactamase cleaves beta lactam rings

What are the two antibiotic resistance mechanisms for beta lactams for gram negative bacteria?

1. Porins weaken import

2. Efflux pumps enhance export

What is the main vancomycin resistance mechanism?

Modification of peptidoglycan with lactate to stop binding

How does the modification of lipid A cause polymixin (colistin) resistance?

Decreases net negative charge

What percent of antibiotics are prescribed for prophylaxis by dentists?

81%

What is the prescription rate of beta lactam from dentists?

75%

What is the first choice of antibiotics for dentists?

Amoxicillin

Why is amoxicillin effective against root canal bacteria and polymicrobial infections?

Broad spectrum

What can be added to amoxicillin if it is ineffective?

Metronidazole

What class of antibiotic is amoxicillin?

Beta lactam

What is the function of metronidazole?

Strand breakage of DNA

What does clindamycin bind to?

50S subunit

What is the risk of using clindamycin?

Increased C. difficile infections

Which is bacteriostatic and bactericidal out of:

• Amoxicillin

• Metronidazole

• Clindamycin

Amoxicillin and metronidazole are bactericidal

clindamycin is bacteriostatic.