Resistance modulating activity of selenoesters in bacteria

Abstract

Infections caused by multidrug resistant bacteria can lead to serious problems regarding the antibacterial therapy. Multidrug resistance (MDR) mechanisms allow resistant bacteria to have limited uptake of drugs, modification of their target molecules, drug inactivation, or release of the drug into the extracellular space by efflux pumps (EPs). Previously, selenoesters have proved to be effective derivatives with anticancer and antimicrobial activities. Based on these results, new selenoesters have been synthesized to achieve a more potent antibacterial activity. Thus, the quorum sensing inhibiting and antibiofilm effects in vitro of fifteen selenoesters (eight ketone-selenoesters and seven cyano-selenoesters) were investigated in this study. The minimum inhibitory concentrations (MICs) of the selenoesters were determined on sensitive and resistant Staphylococcus aureus strains. Biofilms produced by Pseudomonas aeruginosa (CCM, 3955) and S. aureus (ATCC, 25923) were used to evaluate the eruption of mature biofilm and the antibiofilm activity of the compounds. Additionally, two reference strains of Vibrio campbellii were used (BAA1118 and BAA1119) to establish the anti-quorum sensing activity of these novel selenoester derivatives. In this anti-quorum sensing assay, the viability of the cells and the quorum sensing inhibiting effects were determined in the presence of the selenoesters to differentiate between the toxic concentration and the quorum sensing inhibiting concentration. According to the screening of the antibacterial activity, the ketone-selenoesters resulted to be more potent antibacterial compounds than the cyano-selenoesters. The biofilm inhibitory capacity and the ability to disrupt mature biofilms of the derivatives were noteworthy in all the experimental systems considered. Regarding the QS inhibition, four ketone-selenoesters and three cyano-selenoesters among the tested compounds exerted a noteworthy effect on both V. campbellii BAA-1118 and BAA-1119 strains. The results obtained in this work point that these ketone- and cyano-selenoesters could be promising and valuable compounds in the search of novel antibacterials to combat the infections by resistant bacteria, as they have shown a promising anti-biofilm and anti-QS activity. Thus, seleniumcontaining compounds belonging to the family of the selenoester compounds could provide alternative and effective structural motifs to overcome bacterial MDR. Nevertheless, the mode of action of the compounds needs further investigation to be fully understood.