General principles of antibacterials

• How many new antibiotic approvals are expected over the next five years?

  Around 10 new approvals
• Why will the new antibiotic treatments not be sufficient?

  They will add little to the existing arsenal against AMR
• What is the state of antibiotic resistance in environmental bacteria?

  Antibiotic resistance is ancient and widespread
• What is multi-drug resistance (MDR) and where is it common?

  MDR is common in bacteria isolated from Lechuguilla Cave
• What is the intrinsic resistome of Paenibacillus sp. LC231?

  It is resistant to most clinically used antibiotics
• What are the general properties of antibacterial agents?

  • Must kill or inhibit the pathogen
  • Minimize effects on the host
  • Defined by therapeutic and toxic doses
  • Therapeutic index/winodw is crucial
• What is the definition of therapeutic dose?

  The level for successful treatment of infection
• What is the definition of toxic dose?

  The level at which the agent is too toxic for the host
• What is selective toxicity in antibacterial agents?

  It refers to killing or inhibiting pathogens while minimally affecting the host
• What are the five mechanisms of action (MOA) for antibacterial agents?

  1. Inhibitors of cell wall synthesis 2. Disruptors of cell wall/membrane 3. Protein synthesis inhibitors 4. Metabolic antagonists 5. Nucleic acid synthesis/manipulation inhibitors

  
• What is the primary rigid structure of the bacterial cell wall?

  Peptidoglycan

  
• How are antibacterial agents classified by their mechanism of action?

  • Inhibitors of cell wall synthesis
  • Disruptors of cell wall/membrane
  • Protein synthesis inhibitors
  • Metabolic antagonists
  • Nucleic acid synthesis/manipulation inhibitors

  
• What are the repeating sugar molecules that compose peptidoglycan?

  1. acetyl glucosamine (NAG) and N-acetyl muramic acid (NAM)

  
• How is the meshwork of peptidoglycan stabilized?

  By crosslinked small peptide chains
• What enzymes facilitate the linking of NAM subunits in peptidoglycan synthesis?

  Transpeptidases
• What are Penicillin Binding Proteins (PBPs)?

  They are enzymes that facilitate peptidoglycan synthesis

  
• How do β-lactam antibacterials work?

  They bind and inhibit PBPs, disrupting peptidoglycan crosslinking

  
• What is the essential core structure of β-lactams?

  β-lactam ring
• What is the significance of the β-lactam ring's structure?

  It resembles D-alanyl-D-alanine portion of peptide side chains
• What is intrinsic resistance in bacteria?

  Resistance that is inherent to the structure or function of the bacterial species
• What is acquired resistance in bacteria?

  A previously sensitive bacterium acquires a mutation or new genetic material
• What are the classifications of β-lactamases?

  • Ambler classification (A to D) based on amino acid sequences
  • Newer classification (1 through 3b)

  
• What are the subgroups of penicillins?

  Natural penicillin, antistaphylococcal penicillins, aminopenicillins, extended-spectrum penicillins
• What is the mechanism of action of glycopeptides like vancomycin?

  They inhibit cell wall synthesis by forming a complex with peptidoglycan substrates

  
• What is the primary use of fosfomycin?

  Usually for uncomplicated urinary tract infections (UTIs)
• What is the mechanism of action of bacitracin?

  It interferes with peptidoglycan synthesis