Midterm 1 Review

Question 1

Lecture 1: Antibiotics I
- Neosalvarsan
- Gram(-) vs gram(+) structure
- Which is more dangerous? Why?
- 4 sites of antibiotics?
- Bacteriostatic vs Bactericidal in terms of [bacteria]?
- In terms of general mechanism?
- MIC
- MBC
- Which toxic acid was first used to kill bacteria?
- CFU

Answer 1

• Magic bullet against bacterial infections
• Gram(-): Presence of membrane bilayer, thin peptidoglycan layer
  Gram(+): No bilayer, thick peptidoglycan layer
• Gram(-) because of the outer membrane
• DNA/RNA machinery, protein machinery, cell wall synthesis, cell wall synthesis
• Constant [bacteria] vs lower [bacteria]
• Inhibits cell division vs actively kills bacteria
• Minimal inhibitory concentration: No growth, but still present
• Minimal bactericidal concentration: No presence at all
• Arsenic acid
• Colony forming units

Question 2

Lecture 1: Antibiotics I
- When do you use bacteriostatic vs bactericidal?
- How do you measure MIC?
- How do you measure MBC?
- Susceptibility assay
- 2 disadvantages of broad antibiotics
- 1 advantage of broad antibiotic

Answer 2

• Bacteriostatic when non-life threatening and immunocompetent
  Bactericidal when life-threatening or deep-seated infections (endocarditis, meningitis)
• Dilution test
• Dilution + agar test
• 1) Transfer bacterial sample to agar dish
  2) Add drug-impregnated (at different concentrations) disks to the colonies
  3) Wait
• Disrupts microbiota & More pressure to develop resistance
• Administered if you don’t know the exact pathogenic bacteria

Question 3

Lecture 1: Antibiotics I
- Definitive drug therapy
- Empiric therapy
- Prophylactic drug therapy
- 3 outcomes of combining antimicrobial agents
- How do penicillin and aminoglycosides synergize?
- How would each act on its own?
- How do sulfonamides and trimethoprim synergize?
- Which disease is one of the most important resistant diseases?
- 7 ways to develop resistance

Answer 3

• Narrow antibiotic
• Broad antibiotic
• Prevention
• Synergy, Indifference, antagonism
• Penicillin breaks cell wall, allowing aminoglycoside to reach ribosomes and kill bacteria.
• Penicillin would be bacteriostatic whereas aminoglycosides would be ineffective
• Both inhibit Tetrahydrofolic acid syn pathway (notably DNA T synthesis)
• Gonorrhea
• 1) Increased efflux through upregulation of pumps
  2) Decreased influx through downregulation of pores
  3) Target protection
  4) Inactivation of antibiotic
  5) Target

Question 4

Lecture 2: Antibiotics II
- 2 glycans of peptidoglycan
- Penicillin-binding protein function
- 2 domains of PBP
- Function of each
- L or D-aa present in mammalian cells?
- 5 steps in Peptidoglycan syn
- What do b-lactams inhibit?
- Which drug is a known b-lactam?
- Proper term for inhibiting when binding
- Bactericidal or Bacteriostatic?
- Main side effect
- Resistance against b-lactams
- How does it work?
- How can bacteria confer resistance easily?
- Solution?
- Most dangerous b-lactamase
- Neisseria Gonorrhoeae most common resistance?
- 2 other resistances?
- Last recommended treatment against N. Gonorrhoeae

Answer 4

• a) Acetyl glucosamine
  b) Acetyl muramic acid
• Polymerizes peptidoglycan chain
• Transglycosylase and transpeptidase
• a) Chain growth
  b) Cross-linkage
• L-amino acids
• a) UDP-GlcNAc
  b) Becomes UDP-MurNAc
  c) Add 5 aa to UDP-MurNAc (Lipid I)
  d) Add another UDP-GlcNAc to UDP-MurNAc (Lipid II)
  e) Flip to periplasm side
• Transpeptidase
• Penicillin
• Covalent inhibitor
• Bactericidal
• Immediate hypersensitivity by IgE-mediated reactions, usually from the penicillin nucleus
• B-lactamase
• Opens traps
• Metallo-b-lactamase
• Through vectors
• b-lactamase inhibitors
• PBP1 and PBP2 mutation
• a) TEM-1 type b-lactamase
  b) MtrCDE overexpression (efflux pumps)
• Ceftriaxone

Question 5

Lecture 2: Antibiotics II
- Vancomycin type of drug?
- Function?
- Administration?
- Which family of organisms is known to resist Vancomycin?
- How?
- Result?
- Bacitracin type of drug?
- Function?
- Side effect?
- Colistin type of drug?
- Structural function?
- Side effects?
- Administration?
- Daptomycin type of drug?
- Structural function?
- Broad or narrow spectrum?
- Administration
- Fosfomycin type of drug
- Function?
- Aminoglycosides type of drug
- Function
- Why only used for serious infections?
- Don’t couple with which drug?
- 3 resistances
- Tetracyclines type of drug
- Bacteriostatic or Bactericidal?

Answer 5

• Glycopeptide antibiotic
• Wraps around D-Ala-D-Ala
• IV. Oral only if GI infection
• Enterococci
• D-Ala-D-Lac (lactic acid)
• 1000-fold loss of affinity
• Non b-lactam antibiotic
• Wraps around undercaprenyl pyrophosphate, so no recycling
• Nephrotoxic
• Lipopeptide antibiotics
• NH3+ binds to (-) lipopolysaccharide on gram(-) bacteria = forming of pores = ion leakage + less membrane integrity
• Neuro and nephro toxic
• IV
• Lipopeptide
• Forms Ca2+ oligomers = pore-like structures
• Narrow
• IV
• Non b-lactam antibiotic
• Blocks MurA/PEP
• Protein syn inhibs
• Targets 30S ribosomal subunit
• Very toxic
• Colistin
• a) Less influx, more influx
  b) 30S mutation
  c) Enzymatic modification
• Protein syn inhib
• Targets 30S subunit
• Bacteriostatic

Question 6

Lecture 3: Antibacterial III, Antifungal, Antiprotozoal
- Fluoroquinolones type of drug
- Function
- Sulfonamides/Trimethoprim type of drug
- How does each act on the THF syn pathway?
- 2 phases of multidrug therapy. How long in total?
- RIPE is a combo of drugs for which type of organisms?
- 3 molecules targeted by RIPE
- Immune Reconstitution Inflammatory Syndrome (IRIS) characteristic?
- It happens in which treatment?
- Main drugs to manage IRIS?
- What does IRIS cause?

Answer 6

• Antibacterial
• Inhibit Topoisomerase IV and gyrase, stops DNA manipulation
• Antibacterial
• a) Sulfonamides: less substrate
  b) Trimethoprim: competitive inhibitor
• a) Intensive phase: RIPE
  b) Continuation phase: RI
  c) 6 months
• Mycobacteria
• a) Mycolic acid
  b) Arabinogalactan
  c) DNA-dependent RNAP
• Worsening of preexisting infectious processes
• Antiretroviral therapy (ART)
• Corticosteroids
• Tissue damage
• Antifungal
• Binds to ergosterol, makes a pore
• Some because of amphipathic nature
• Insert Amphotericin B in liposome membrane
• Antifungal
• Triazole/imidazole inhibit ergosterol-synthesizing enzymes
• Inhibit fungal cell wall (D-glucan)
• Large cyclic peptides linked to a long FA
• Candida auris
• Echinocandins
• Liposomal amphotericin B

Question 7

Lecture 3: Antibacterial III, Antifungal, Antiprotozoal
- Amphotericin B type of drug?
- Function?
- Toxicity?
- Solution?
- Azoles type of drug?
- Function?
- Echinocandins type of drugs?
- Function?
- Structure
- Organism discussed in class
- Empiral choice drug?
- Alternative?
- Quinone and Cloroquine type of drug?
- Function?
- What’s toxic about heme?
- 2 organisms that cause malaria
- Life cycle of P. falciparum

Answer 7

• Antifungal
• Binds to ergosterol, makes a pore
• Some because of amphipathic nature
• Insert Amphotericin B in liposome membrane
• Antifungal
• Triazole/imidazole inhibit ergosterol-synthesizing enzymes
• Inhibit fungal cell wall (D-glucan)
• Large cyclic peptides linked to a long FA
• Candida auris
• Echinocandins
• Liposomal amphotericin B
• Antiprotozoal
• Inhibits heme polymerase that convert heme into hemozoin
• The iron and reactive oxygen species (ROS)
• Plasmodium falciparum and Plasmodium vivax
• a) Inject sprozoite
  b) Sporozoite goes into lover and enter hepatocytes
  c) 10K merozoites released and infect RBCs
  d) Asexual continue RBC infection, sexual gets taken by uninfected mosquito
  e) In mosquito’s GI system, gametes –> zygote –> ookinete –> oocysts –> spirozoites

Question 8

Lecture 4: Antiviral
- 6 groups of drugs for HIV
- What do boosting agents do
- Which boosting agent does not work on its own?
- ART initial regimens
- ART Pre-exposure prophylaxis (PrEP)
- Influenza 3 steps infection
- Group of drug for influenza?
- 3 groups of drugs for coronaviruses
- Nirmatrelvir/Ritonavir type of drug
- Function
- Remdesivir type of drug
- Stalls chain growth with its 2 hydroxy groups after adding 3 nucleotides
- Dexomethasone type of drug?
- Do antiviral drugs work in severe diseases?
- How is remdesivir better than nirmatrelvir/ritonavir?

Answer 8

• NRTI, NtRTI, NNRTI, integrase inhibitors, PI, boosting agents
• inhibit P-glycoproteins and CYP3A4
• Cobicistat
• 1 Integrase inhib + 2 NRTI
• PI/booster + 2 NRTI
• a) Hemagglutinin binds to cell surface glycans (sialic acid precisely)
  b) Virus entry
  c) Cleave sialic acid to dissociate from cell with neuraminidase
• Neuraminidase inhibitors
• a) Viral protease inhibitor
  b) RNA-dependent RNAP inhib
  c) Host-directed immune modulators
• Viral protease inhib
• Inhibits Cys145 on coronavirus Mpro (cysteine protease)
• RNA-dependent RNAP inhib
• Host-directed immune modulator - corticosteroid
• No
• Less DDI and not nephrotoxic