RX511 Introduction to Antibiotics and Drug Resistance

What is murein?

A glycoprotein on the bacterial cell wall

What are the cell wall synthesis inhibitors?

- Penicillins

- Carbapenems

- Monobactams

- Vancomycin

What subunits do bacterial ribosomes have?

- 50S

- 30S

- Combined 70S

What are the protein synthesis inhibitors?

- Aminoglycosides

- Tetracyclines

- Macrolides

- Clindamycin

- Chloramphenicol

- Streptogramins (-pristin)

What drug classes inhibit DNA gyrase (topoisomerase II)?

- Quinolones

- Fluoroquinolones

Which class of antibiotics blocks peptidoglycan cross-linking and transpeptidation?

Beta-lactams

Which antibiotic causes DNA strand breakage via radical intermediates?

Metronidazole

What mutation provides innate resistance to beta-lactams?

No peptidoglycan cell wall

Which bacteria are innately resistant to aminoglycosides?

Anaerobes

What do aminoglycosides require for transport across the cell membrane?

Oxygen

What bacteria are susceptible to metronidazole?

Anaerobes, because they produce radical intermediates

Conjugation

Gene transfer through direct cell-to-cell contact

Transduction

DNA transfer from a phage (bacterial virus) from a previous host bacterium

Transformation

Bacteria incorporate DNA released into the environment from other bacterial cells

What mutations reduce entry of drug into the pathogen?

- Gram-negative membrane

- Change in or loss of porin channels

What are the MFS pumps?

- Use proton motive force for energy

- TetA

- MefA/MefB

What are the RND pumps?

- Span Gram-negative membrane

- AcrAB-TolC

- MexAB-OprM

- ABC

Which efflux pump exports tetracycline?

TetA

Which efflux pump exports macrolides?

MefA/MefB

What does the AcrAB-TolC pump export?

- Fluoroquinolones

- Chloramphenicol

- Tetracyclines

- Beta-lactams

What does the MexAB-OprM pump export?

- Carbenicillin

- Fluoroquinolones

- Tetracyclines

- Macrolides

- Chloramphenicol

What does the ABC transporter export?

- Aminoglycosides

- Beta-lactams

- Fluoroquinolones

- Tetracyclines

- Polypeptides

- Chloramphenicol

The mecA mutation prevents MRSA from being susceptible to which antibiotics?

- Penicillins

- Cephalosporins

The BacA mutation prevents susceptibility to which antibiotics?

Polypeptides

Methylating A2058 in 23S rNA of the 50S subunit blocks which antibiotics?

Macrolides

Mutating the 16S rNA blocks which antibiotic from binding to the 30S decoding site?

Aminoglycosides

Mutating rpsL and rpD prevents which antibiotic from binding to the 30S subunit?

Streptomycin

Mutating the gyrA and parC genes on DNA gyrase and topoisomerase IV prevents which antibiotic from binding?

Ciprofloxacin

Replacing D-Ala-D-Ala with D-Ala-D-Lac in peptidoglycan precursors (vanA operon) strongly reduces which antibiotic's binding affinity?

Vancomycin

Acetyltransferases (AAC) prevent 30S ribosomal binding for which antibiotic?

Gentamicin

Phosphotransferases (APH) prevent 30S ribosomal binding for which antibiotic?

Kanamycin

Nucleotidyltransferases (ANT) prevent 30S ribosomal binding for which antibiotic?

Tobramycin

Extended-spectrum beta-lactamases prevent PBP binding for which antibiotics?

Third-generation cephalosporins (ceftriaxone, ceftazidime)

Carbapenemases prevent PBP binding for which antibiotics?

- Meropenem

- Imipenem

What can inactivate polypeptide antibiotics?

Enzymatic cleavage

Which antibiotics inhibit dihydropteroate synthase (DHPS)?

Sulfonamides

Which antibiotic inhibits dihydrofolate reductase (DHFR)?

Trimethoprim

How do bacteria circumvent sulfonamides and trimethoprim?

- Folate pathway bypass, continuing PABA incorporation

- Absorbing exogenous thymidine, bypassing thymidylate synthesis

Bacteria without a cell wall are resistant to which antibiotic classes?

- Beta-lactams

- Glycopeptides