Home
Resources
Publications
A New Class of Synthetic Retinoid Antibiotics Effective Against Bacterial Persisters

A New Class of Synthetic Retinoid Antibiotics Effective Against Bacterial Persisters

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, etc.

Nature. 2018 Apr 5;556(7699):103-107.

PMID: 29590091

Abstract:

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 anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP125316601	CD437		125316-60-1	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: