Resistance mechanisms occur in almost all clinical bacterial isolates and represent one of the most worrisome health problems worldwide. Bacteria can form biofilms and communicate through quorum sensing (QS), which allow them to develop resistance against conventional antibiotics. Thus, new therapeutic candidates are sought. We focus on alkylglycerols (AKGs) because of their recently discovered quorum sensing inhibition (QSI) ability and antibiofilm potential. Fifteen natural enantiopure AKGs were tested to determine their effect on the biofilm formation of other clinical bacterial isolates, two reference strains and their QSI was determined using Chromobacterium violaceum ATCC 12472. The highest biofilm inhibition rates (%) and minimum QS inhibitory concentration were determined by a microtiter plate assay and ciprofloxacin was used as the standard antibiotic. At subinhibitory concentrations, each AKG reduced biofilm formation in a concentration-dependent manner against seven bacterial isolates, with values up to 97.2%. Each AKG displayed QSI at different levels of ability without affecting the growth of C. violaceum. AKG (2S)-3-O-(cis-13’-docosenyl)-1,2-propanediol was the best QS inhibitor (20 μM), while (2S)-3-O-(cis-9’-hexadecenyl)-1,2-propanediol was the least effective (795 μM). The results showed for the first time the QSI activity of this natural AKG series and suggest that AKGs could be promising candidates for further studies on preventing antimicrobial resistance.

Inhibition of quorum sensing by compounds from two Eunicea species and synthetic saturated alkylglycerols

Alkylglycerols (AKGs) are bioactive natural compounds that vary by alkyl chain length and degree of unsaturation, and their absolute configuration is 2S. Three AKGs (5l–5n) were synthesised in enantiomerically pure form, and were characterised for the first time together with 12 other known and naturally occurring AKGs (5a–5k, 5o). Their structures were established using ¹H and ¹³C APT NMR with 2D-NMR, ESI-MS or HRESI-MS and optical rotation data, and they were tested for their antibacterial and antibiofilm activities. AKGs 5a–5m and 5o showed activity against five clinical isolates and P. aeruginosa ATCC 15442, with MIC values in the range of 15–125 µg/mL. In addition, at half of the MIC, most of the AKGs reduced S. aureus biofilm formation in the range of 23%–99% and P. aeruginosa ATCC 15442 biofilm formation in the range of 14%–64%. The antibiofilm activity of the AKGs assessed in this work had not previously been studied. Graphical Abstract