Inhibition of phospho-MurNAc-pentapeptide translocase (MraY) by nucleoside natural product antibiotics, bacteriophage ϕX174 lysis protein E, and cationic antibacterial peptides

Abstract

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Insights into the Target Interaction of Naturally Occurring Muraymycin Nucleoside Antibiotics

“…Antibacterial activities of muraymycins against a range of pathogens have been reported before, [8c,9a,b] so we mainly aimed to confirm some of the previously reported data and to comparatively study activities against an efflux-deficient bacterial strain. In our hands, muraymycin A1 3 was the only congener with notable activity against S. aureus , which was in good agreement with previously published data.…”

“…[8] Muraymycins (e.g., compounds 3 – 8 , Table 1) were discovered as a collection of 19 structurally related, secondary metabolites from Streptomyces sp. in 2002.…”

“…First insights into the biosynthesis of these antibacterial natural products have already been obtained and are summarized elsewhere. [8c] …”

Muraymycin Nucleoside Antibiotics: Structure-Activity Relationship for Variations in the Nucleoside Unit

“…Nucleoside antibiotics are naturally produced secondary metabolites acting as MraY inhibitors. Several subclasses such as muraymycins, mureidomycins, tunicamycins, liposidomycins, and capuramycins have been reported [13][14][15][16]. Our research on nucleoside antibiotics mainly focusses on muraymycins which were isolated from Streptomyces sp.…”

Peptidoglycan pathways: there are still more!

“…This particular sub-structure is a key element in their MraY inhibitory properties, which are backed by their ability to recognize and competitively bind to UDP-Mpp binding sites on MraY. 48,52,54,55 For further information, the SAR details of this group have been reviewed by T. D. Bugg et al 56 Unfortunately, the poor physicochemical properties are a perennial limitation that has prevented any further clinical development.…”