Objectives: - Define terms essential to drug/action resistance comprehension;

• Exemplify main genes and main phenomena related to resistance, tolerance and persistence in bacteria;
• Apply some contribution about these theme in creation of experimental design;
• Evaluate the implication of tolerance and persistence to the host.

Topics:

• Types of resistance

  • mutations in the drug target. (The difference between the genotypic and phenotypic resistance)
  • enzymatic activity that directly inactivates the antibiotic
  • loss of drug-activation
  • barrier mechanisms (reduced uptake or increased efflux)
  • target overexpression,

• How not to be confused about resistance, tolerance and persistence? Because the main focus of the course is Mycobacteria, we suggest to add "Dormancy" within the definitions.

• Evolutionary and advantages conferred by these model of survival

• Antimicrobial pharmacokinetics and drug fluctuations - the extrapolation from in-vitro to in-vivo

• Minimum duration for killing (MDK) (Diferences in killing profiling graphically represented).

• Drug Tolerance is an Important Barrier to Shortening TB Treatment

  • Pyrazinamide and its role against treatment relapse
  • Why we use drug combination regimens?
  • Drug-Specific Tolerance Mechanisms

• What is a efflux pump?

  • Main efflux pumps in mycobacteria and t

• Therapeutic implications of drug tolerance

• Efflux pumps inhibitors, mode of action: (definitions and examples)

  (1) direct binding and inhibition of pump assembly or function;

  (2) disruption of the transmembrane gradients utilized by secondary transporters

  (3) inhibitor binding to the antimicrobial compound;

  (4) competition for efflux

REFERENCES

15. Mechanism of grug action, grug resistance and drig tolerance.pdf

nrmicro.2016.34 (1).pdf

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