A triple‐targeting inhibitory activity of Rose Bengal on polysaccharide biosynthesis of Burkholderia pseudomallei

• Published in: Archiv der Pharmazie (Weinheim) 2021-06, Vol.354 (6), p.e2000360-n/a
• Main Authors: Kim, Suwon, Jo, Seri, Kim, Mi‐Sun, Shin, Dong H.
• Format: Article
• Language: English
• Subjects: 3‐deoxy‐d‐manno‐oct‐2‐ulosonic acid cytidylyltransferase (KdsB); Biosynthesis; d‐glycero‐α‐ d‐manno‐heptose‐1‐phosphate guanylyltransferase (HddC); d‐glycero‐β‐ d‐manno‐heptose‐1‐phosphate adenylyltransferase (HldC); Rose Bengal; sugar nucleotidyltransferases
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.202000360

Sugar nucleotidyltransferases (SNTs) participate in various biosynthesis pathways constructing polysaccharides in Gram‐negative bacteria. In this study, a triple‐targeting inhibitory activity of Rose Bengal against SNTs such as d‐glycero‐α‐d‐manno‐heptose‐1‐phosphate guanylyltransferase (HddC), d‐glycero‐β‐d‐manno‐heptose‐1‐phosphate adenylyltransferase (HldC), and 3‐deoxy‐d‐manno‐oct‐2‐ulosonic acid cytidylyltransferase (KdsB) from Burkholderia pseudomallei is provided. Rose Bengal effectively suppresses the nucleotidyltransferase activity of the three SNTs, and its IC50 values are 10.42, 0.76, and 5.31 µM, respectively. Interestingly, Rose Bengal inhibits the three enzymes regardless of their primary, secondary, tertiary, and quaternary structural differences. The experimental results indicate that Rose Bengal possesses the plasticity to shape its conformation suitable to interact with the three SNTs. As HddC functions in the formation of capsular polysaccharides and HldC and KdsB produce building blocks to constitute the inner core of lipopolysaccharide, Rose Bengal is a potential candidate to design antibiotics in a new category. In particular, it can be developed as a specific antimelioidosis agent. As the mortality rate of the infected people caused by B. pseudomallei is quite high, there is an urgent need for specific antimelioidosis agents. Therefore, a further study is being carried out with derivatives of Rose Bengal. Sugar nucleotidyltransferases (SNTs) participate in various polysaccharide biosynthesis pathways. In this study, a triple‐targeting inhibitory activity against three SNTs of Rose Bengal (RB) is provided. As RB possesses the plasticity to shape its conformation to interact with the SNTs, its derivatives can be developed as therapeutics to cure melioidosis.