Antibiotic chemistry 1

• What are the main classes of β-lactam antibiotics?

  1. Penicillin 2) Cephalosporins 3) Cephamycins
• Which additional classes are included in β-lactam antibiotics?

  Carbapenems and monobactams
• What structural feature do all classes of β-lactam antibiotics share?

  Each class contains a β-lactam ring.
• How does the β-lactam ring function in relation to bacterial cell walls?

  It mimics the D-Ala-D-Ala dipeptide involved in peptidoglycan cross-linking.
• Why is the β-lactam ring considered highly strained?

  Because it makes the β-lactam bond electrophilic.
• What is the role of penicillin-binding proteins (PBPs) in the action of β-lactam antibiotics?

  They are not substrate mimics for the β-lactam ring.
• What happens when a stable acyl-enzyme complex is formed with β-lactam antibiotics?

  It blocks the enzyme active site and removes the nucleophile, leading to irreversible inhibition.
• What is the result of bacterial lysis in the presence of β-lactam antibiotics?

  It leads to the death of the bacteria.
• How does a high level of PBPs affect bacterial lysis?

  It results in decreased lysis of the bacteria.
• What is one mechanism of resistance to β-lactam antibiotics?

  Target modification of PBPs is important for methicillin resistance.
• How does methicillin resistance occur in Staphylococcus aureus?

  Penicillin binds weakly to the altered PBP in MRSA.
• What is the most important mechanism of penicillin resistance?

  β-lactamases
• What do β-lactamases do in relation to penicillin resistance?

  They mediate most penicillin resistances and other β-lactam antibiotics.
• What is an example of a Class A β-lactamase?

  TEAM-ona-2
• What is an example of a Class B β-lactamase?

  NDM-1
• What is a characteristic of Class D β-lactamases?

  They have an extended spectrum of activity.
• What is one strategy for overcoming β-lactamase resistance?

  Develop new antibiotics that are resistant to hydrolysis.
• Why can resistance to β-lactam antibiotics develop quickly in hospitals?

  Because of the selective pressure and high use of antibiotics.
• What is a common issue with patients taking antibiotics?

  Patients often fail to complete the full course of antibiotics.
• What is one method for discovering new antibiotics?

  Natural product screening programs require screening of mammalian sources.
• What does manipulating biosynthetic pathways involve in antibiotic discovery?

  It involves creating semi-synthetic antibiotics from natural products.
• How do penicillin N and penicillin G differ in their antibiotic activities?

  They have different antibiotic activities.
• What is required to make semi-synthetic penicillins?

  6-aminopenicillanic acid (6-APA) is needed.
• How is semi-synthetic penicillin produced?

  By chemical acylation of 6-APA.
• Why is 6-APA difficult to extract?

  Because it is zwitterionic.
• How can the yield of penicillin be increased in production strains?

  By changing culture media and mutating penicillin fungi.
• What are some examples of semi-synthetic penicillins?

  Amoxicillin, ampicillin, methicillin, cloxacillin, flucloxacillin.