Lecture 15_250 review

Exam 2 Review Topics

Lecture 15: Antimicrobial Resistance

• Antimicrobial resistance refers to the ability of microbes to resist the effects of drugs that once killed them or inhibited their growth.

How do we get antibiotic-resistant microbes?

• Selective Pressure Role:

  • Occurs when antibiotics are used, leading to the survival of resistant bacteria over sensitive ones.

• Genetic Mutation + Vertical Transfer Role:

  • Mutations can occur in bacterial DNA, leading to resistance, then passed to offspring through vertical gene transfer.

• Horizontal Gene Transfer Role:

  • Resistance genes can be transferred between bacteria through mechanisms such as transformation, transduction, and conjugation.

• Bacteriostatic and Bactericidal Hypotheses:

  • Bacteriostatic drugs inhibit growth, while bactericidal drugs kill bacteria directly. Understanding these mechanisms helps in developing strategies to counter resistance.

Four Mechanisms for Drug Resistance

1. Modification of Drug:

   • How?: Bacteria can produce enzymes that chemically alter the drug, rendering it ineffective.

   • Examples?: Beta-lactamases that break down penicillins.

2. Modification of Antimicrobial Target:

   • How?: Changes in the structure of the target site of the drug can prevent binding.

   • Examples?: Mutation of penicillin-binding proteins in MRSA, which reduces drug efficacy.

3. Prevention of Drug Penetration:

   • How?: Alterations in the cell membrane can prevent drug entry.

   • Examples?: Reduced permeability of the outer membrane in gram-negative bacteria.

4. Prevention of Drug Accumulation:

   • How?: Efflux pumps actively remove the drug from the cell.

   • Why do all bacteria have efflux, and what is its purpose:

     • To eliminate toxic substances that may harm the cell.

   • Examples?: Efflux pumps for tetracycline in certain bacteria.

Multi-Drug-Resistant Microbes

• What defines a superbug/MDR?:

  • A superbug, also known as multi-drug-resistant (MDR), refers to bacteria that are resistant to multiple antibiotic classes, making infections particularly difficult to treat.

• What is cross-resistance?:

  • Cross-resistance occurs when a single mechanism of resistance to one drug confers resistance to other drugs.

MRSA (Methicillin-Resistant Staphylococcus aureus)

• What is it?:

  • A strain of Staphylococcus aureus that has developed resistance to methicillin and other beta-lactam antibiotics.

• By what mechanism are these bacteria resistant to all B-lactams?:

  • Changes in penicillin-binding proteins render them ineffective against MRSA strains.

VRSA (Vancomycin-Resistant Staphylococcus aureus)

• What is it?:

  • A strain of Staphylococcus aureus that is resistant to the antibiotic vancomycin, a last-resort drug for treating serious infections.

• By what mechanism are these bacteria resistant to vancomycin?:

  • Genetic changes produce an altered target (D-Ala-D-Ala to D-Ala-D-Lactate) reducing the drug's binding affinity.

• How do we think vanA was originally transferred to S. aureus?:

  • Possible acquisition through horizontal gene transfer from enterococci, where the vanA gene originated.

  • What horizontal transfer steps are involved?:

    • Transformation (uptake of naked DNA), conjugation (direct transfer of DNA), and transduction (phage-mediated transfer).

Viruses

• Antigenic Drift vs Antigenic Shift:

  • Antigenic Drift: Small mutations in virus genes lead to changes in surface proteins, causing gradual changes in virulence and immune evasion.

  • Antigenic Shift: Major changes resulting from gene reassortment between different viral strains can lead to the emergence of new viruses against which populations have little or no immunity.