Centre for New Antibacterial Strategies (CANS) seminar by Professor Dan I. Andersson

Dan I. Andersson has been a professor of Medical Bacteriology at Uppsala University, Sweden, since 2004. Before this, he worked as Section Chief at the Swedish Institute for Infectious Disease Control, Solna, Sweden. He uses genetics and experimental evolution to study genome stability and variability, development of antibiotic resistance and evolution of new genes. Particular focus areas with regard to antibiotic resistance are heteroresistance, antibiotic interactions and the importance of weak antibiotic selection as a driver of resistance evolution.

Title of presentation: Unstable and transient antibiotic resistance

Abstract:

Antibiotic heteroresistance (HR), first described in the 1940s, is a phenotype in which a bacterial isolate contains subpopulations of cells that exhibit increased antibiotic resistance in comparison to the main population and that can be enriched under antibiotic selection. HR occurs in both Gram-positive and Gram-negative bacteria and based on animal and clinical studies it has been suggested as one factor that contributes to treatment failure. HR is prevalent among various Gram-negative bacteria and approximately 27% of all isolates show HR to one or several antibiotics. The most common mechanism of HR involves spontaneous gene amplification of weakly expressed resistance genes (encoding for example an antibioticmodifying enzyme) whose increased dosage and overproduction generate the resistant subpopulation. These transient tandem gene amplifications are intrinsically unstable and costly, and therefore lost in the absence of antibiotic selection. As a result, HR is difficult to routinely detect in the clinical setting, often resulting in misdiagnosis of HR isolates as susceptible.

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