New insights into antimicrobial tolerance

Antimicrobial tolerance is

the ability of a normally susceptible, often dormant, bacterial population to survive, rather than die, during extended exposure to bactericidal drugs without changing their minimum inhibitory concentration (MIC). Unlike resistance, which allows growth despite drugs, tolerant bacteria temporarily endure treatment, leading to chronic, relapsing infections and potential evolution into resistant strains.

 

The following video provides some insights, looking at recent research: 

 

 

 

Key Aspects of Antimicrobial Tolerance:

• Mechanism: Often involves low metabolic states (dormancy) or specialized stress responses (e.g., SOS DNA damage repair, cell envelope stress systems).
• Persistence vs. Tolerance: Tolerance typically describes the survival of the entire population, whereas persistence describes a small subpopulation ("persister cells") that survives high drug concentrations.
• Clinical Impact: Contributes to treatment failure in infections like tuberculosis, as bacteria "reawaken" once the antibiotic is removed.
• Distinction from Resistance: Tolerant cells do not grow in the presence of the drug, unlike resistant cells.
• Evolutionary Role: Tolerance can serve as a stepping stone for the development of full resistance.

Common Tolerance Mechanisms:

• Metabolic Slowdown: Reduced metabolic rate makes cells less susceptible to metabolic-dependent antibiotics.
• Biofilm Formation: Bacteria in biofilms often exhibit higher tolerance due to nutrient limitation and stress responses.
• Stress Responses: Activation of pathways (e.g., SOS response) that repair damage caused by antibiotics.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)