Natural products from food sources can alter the spread of AMR plasmids in Enterobacterales

Antimicrobial resistance (AMR) poses a significant threat to global public health. Notably, resistance to carbapenem and extended-spectrum β-lactam antibiotics in Gram-negative bacteria is a major impediment for the treatment of infections. Genes responsible for resistance to these antibiotics are frequently carried on plasmids, which can transfer between bacteria. Therefore, exploring strategies to prevent this transfer and/or the prevalence of AMR plasmids is timely and pertinent. Here, we show that certain natural product extracts and associated pure compounds can reduce the transmission of AMR plasmids into new bacterial hosts. Using our established high-throughput fluorescence-based screen we found that the natural products were more active in reducing transmission of the IncK plasmid pCT in Escherichia coli ST131, compared to Klebsiella pneumoniae Ecl8 carrying the IncFII plasmid pKpQIL. Furthermore, we found that the natural product rottlerin was more active in K. pneumoniae than in E. coli . Importantly, rottlerin was also associated with a reduced number of transconjugant bacteria in a clinical K. pneumoniae isolate harbouring a bla _NDM-1 plasmid. Together, these results demonstrate the potential of natural products as promising anti-plasmid agents.