Bromopyrrole Alkaloids with the Inhibitory Effects against the Biofilm Formation of Gram Negative Bacteria.

Jingyuan Sun,Jiru Wu,Nicole Voogd,Wei Cheng,Wenhan Lin,Bang An

doi:10.3390/md16010009

Abstract

Anti-biofilm assay guided fractionation of the marine sponge Stylissa massa revealed the butanol soluble fraction that was possessing the inhibitory activity toward the biofilm formation of bacterium E. coli. Chromatographic separation of the bioactive fraction resulted in the isolation of 32 bromopyrrole alkaloids, including six new alkaloids, named stylisines A–F (1–6). The structures of new alkaloids were established by comprehensive analyses of the two-dimensional (2D) NMR (COSY, HMQC, and HMBC) and the high resolution electrospray ionization mass spectroscopy (HRESIMS) data, while the absolute configurations were determined by the X-ray diffraction and the electronic circular dichroism (ECD) data. Bioassay results indicated that phakellin-based alkaloids, including dibromoisophakellin and dibromophakellin, significantly reduced the biofilm formation of the bacterium E. coli. Present work provided a group of new natural scaffolds for the inhibitory effects against the biofilm formation of E. coli.

Highlights

Planktonic bacteria attached onto solid surfaces, creating a complex community of bacteria to form a biofilm, which protects bacteria against antibiotics and causes many recalcitrant infections, as well as resistance to antibiotics [1,2,3,4]
To the best of our knowledge, this study uncovered the largest numbers of brominated alkaloids with diverse scaffolds that were derived from marine sponge S. massa, implying more complexity of ecological environments, such as high biodiversity of predators, competitors, and overgrowths, as well as natural sponge-microbial associations in tropical sea water [49]
IR spectra were determined on a Thermo Nicolet Nexus 470 FT-IR spectrometer. 1D and 2D NMR spectra were recorded on a Bruker Avance 400 NMR spectrometer (400 MHz for 1 H and 100 MHz for 13 C, respectively)

Summary

Introduction

Planktonic bacteria attached onto solid surfaces, creating a complex community of bacteria to form a biofilm, which protects bacteria against antibiotics and causes many recalcitrant infections, as well as resistance to antibiotics [1,2,3,4]. Most bacteria are likely to form surface-attached biofilm communities as a survival strategy. Pathogenic biofilms pose a challenge because they enhance resistance to conventional antibiotics, and to host defenses and external stresses. They are difficult to control in medical and industrial settings. One epibacterial defense strategy for sponge-symbiont community is to produce bioactive secondary metabolites in order to outcompete other bacteria in the water column from causing infection or biofouling [9,10,11,12,13,14].

Methods

Results

Discussion

Conclusion