Chapter 10: AntiMicrobial Treatment (Primary sites of action down to spectrum of activity of penicillin)

Why is the goal of chemotherapy?

disrupt the structure or function of an organism to the point where it can no longer survive

What are the 5 antimicrobial drug categories? (Based on what they target)

1. Inhibition of cell wall synthesis (targeting repair/synthesis; ex: -cillins)

2. Inhibition of nucleic acid (RNA and DNA) structure and function (enzymes in synthesis are different than those in human cells)

3. Inhibition of the ribosome in protein synthesis (Bacterial enzymes are 70S and Humans are 80S)

4. Interference with cytoplasmic membrane structure or function

5. Inhibition of folic acid synthesis (Humans don’t have folic acid and effects enzymes in this synthesis)

Is there 100% selective toxicity of drugs when targeting inhibition of the ribosome in protein synthesis?

No, because some ribosomes in humans are 70 S for example mitochondrial ribosomes

What was the three main types of drugs that target the cell wall?

1. Penicillins

2. Cephalosporins

3. Carbapenems

Within the three main types of drugs that target the cell wall what are the drugs in the categories? Additionally state if they are semisynthetic or natural or a combination if necessary.

1. Penicillins

• Penicillins G and V (natural penicillins)

• Ampicillin, amoxicillin (semisynthetic)

• Methicillin

• Clavulanic acid (Augmentin) (Combination of Amoxicillin and Clv. Acid)

2. Cephalosporins

3. Carbapenems

• Vancomycin

What are the three drug types that target protein synthesis and what they do they do? What are some examples of them?

1. Aminoglycosides: insert on sites on the 30S subunit of ribosome and cause the misreading of the mRNA (misreads codons), leading to abnormal proteins

• Streptomycin

2. Tetracyclines: block the attachment of tRNA to ribosome and stop further protein synthesis

• Tetracycline

3. Macrolides: inhibit translocation (glide movement of ribosome along mRNA) of the subunit during translation (erythromycin)

• Erythromycin, azithromycinhromycin

What are the steps of protein synthesis? Listen to voiceover and look at the page I created

1. DNA transcribed into mRNA codons as long strands until a stop codon

2. Ribosome binds to mRNA (bigger unit is 50S and smaller is 30S)

3. AAs attach to tRNA

4. tRNA moves from the cytoplasm to the ribosome

5. Ribosome slides down mRNA while reading the codons

6. As it reads the ribosome connects AAs together for the corresponding tRNA anticodon

7. tRNAs exit the ribosome and leaves the AAs

What is the structure of the ribosome in bacteria? How many tRNAs are in the ribosome at one time?

• A bacterial ribosome that is 70S is made up of two subunits

• The subunits include: 50S subunit (larger subunit) and 30S (Smaller subunit) (IT DOESNT MATTER THAT THEY DONT ADD UP TO 70S)

• 2 tRNAs are in the ribosome to link them together

What are the drugs that target folic acid synthesis? What do they interfere with and how? What production is eventually stopped?

1. Sulfonamides:

• interfere with folic acid metabolism

• by blocking enzymes required for the synthesis of folic acid and

• eventual production of DNA, RNA, and amino acids

What are the two categories of drugs that target DNA or RNA? Which of the two is only in bacterial cells and what enzyme does it target?

1. Quinolones: inhibit DNA unwinding enzymes or helicases, thereby stopping DNA transcription (synthesis/replication)

• Inhibit helicases in only bacterial cells

2. Rifampin: inhibits RNA polymerase (synthesis/transcription)

What are the drugs that target cytoplasmic or cell membranes? What bacteria does it target specifically? What are some examples? Do these drugs have selective toxicity?

1. Polymyxins: interact with membrane phospholipids; distort the cell surface and cause leakage from cytoplasm, particularly in gram-negative bacteria

• Ex: Polymyxin B And Daptomycin

• They don’t have selective toxicity b/c they are going after the cell membrane which both human and bacterial cells have

What are the two terms for spectrum of activity for antibiotics? Do most bacteria affect our normal microbiomes?

• Broad-spectrum drugs: effective against more than one group of bacteria

• Narrow-spectrum drugs: target a specific group

• Most bacteria affect our normal microbiome