Rottlerin: An antibacterial agent and inhibitor of plasmid-mediated antibiotic resistance transfer

Analysis of the phytochemical and antimicrobial properties of Mallotus phillipensis revealed rottlerin (1) as the primary active agent in a chloroform extract from the plant. Rottlerin had notable activities against Staphylococcus aureus (0.625–4µg/ml) and good to moderate activities against Escherichia coli (32µg/ml) and Mycobacteriun bovis (100µg/ml) respectively. Remarkably, rottlerin at sub-inhibitory concentrations inhibited by >1000-fold the transfer of broad-host range plasmid pKM101 between E. coli isolates. The anti-plasmid activity appeared to be specific, the transfer plasmids of different types, such as TP114, were not inhibited by such the same extent although the complete range of activity has yet to be determined. Rottlerin appears to have dual properties: direct anti-bacterial activity and the capacity to inhibit antimicrobial resistance spread. This is vital in the fight against multi-resistant bacteria and exploiting the mechanism of plasmid transfer could potentially lead to the development of more universal antimicrobial agents.