Effect of chemotherapeutic agents on natural transformation frequency in Acinetobacter baylyi

Abstract

Natural transformation is the ability of a bacterial cell to take up extracellular DNA which is subsequently available for recom-bination into the chromosome (or maintenance as an extrachromosomal element). Like other mechanisms of horizontal gene transfer, natural transformation is a significant driver for the dissemination of antimicrobial resistance. Recent studies have shown that many pharmaceutical compounds such as antidepressants and anti-inflammatory drugs can upregulate transformation frequency in the model species Acinetobacter baylyi. Chemotherapeutic compounds have been shown to increase the abundance of antimicrobial resistance genes and increase colonization rates of potentially pathogenic bacteria in patient gastrointestinal tracts, indicating an increased risk of infection and providing a pool of pathogenicity or resistance genes for transformable commensal bacteria. We here test for the effect of six cancer chemotherapeutic compounds on A. baylyi natural transformation frequency, finding two compounds, docetaxel and daunorubicin, to significantly decrease transformation fre-quency, and daunorubicin to also decrease growth rate significantly. Enhancing our understanding of the effect of chemothera-peutic compounds on the frequency of natural transformation could aid in preventing the horizontal spread of antimicrobial resistance genes.