A new class of synthetic retinoid antibiotics effective against bacterial persisters

A new class of synthetic retinoid antibiotics effective against bacterial persisters Nature 556, 7699 (2018). doi:10.1038/nature26157 Authors: Wooseong Kim, Wenpeng Zhu, Gabriel Lambert Hendricks, Daria Van Tyne, Andrew D. Steele, Colleen E. Keohane, Nico Fricke, Annie L. Conery, Steven Shen, Wen Pan, Kiho Lee, Rajmohan Rajamuthiah, Beth Burgwyn Fuchs, Petia M. Vlahovska, William M. Wuest, Michael S. Gilmore, Huajian Gao, Frederick M. Ausubel & Eleftherios Mylonakis A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant ‘persister’ subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans–MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain ...
Source: Nature - Category: Research Authors: Tags: Letter Source Type: research