Butenolide, a Marine-Derived Broad-Spectrum Antibiofilm Agent Against Both Gram-Positive and Gram-Negative Pathogenic Bacteria

Qi Yin,Lv Zhang,Yu Zhang,Jinyou Liang,Zhang-Li Hu,Ying Xu,Weipeng Zhang

doi:10.1007/s10126-018-9861-1

Abstract

Bacterial biofilm can cause nosocomial recurrent infections and implanted device secondary infections in patients and strongly promotes development of pathogenic drug resistance in clinical treatments. Butenolide is an effective anti-macrofouling compound derived from a marine Streptomyces sp., but its antibiofilm efficacy remains largely unexplored. In the present study, the antibiofilm activities of butenolide were examined using biofilms formed by both Gram-positive and Gram-negative pathogenic model species. Four Escherichia coli strains, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA) were used as targets in antibiofilm assays that examined the effects of butenolide, including the following: (i) on bacterial growth; (ii) in inhibiting biofilm formation and eradicating mature biofilm; (iii) on biofilm structures. In addition, the synergistic effect between butenolide with tetracycline was also examined. Butenolide not only effectively inhibited the biofilm formation but also eradicated pre-formed biofilms of tested bacteria. Fractional inhibitory concentration index (FICI) indicated that butenolide was a potential tetracycline enhancer against E. coli, P. aeruginosa, and MRSA. These results indicated that butenolide may hold a great potential as an effective antibiofilm agent to control and prevent biofilm-associated infections in future clinical treatments.

Highlights

Introduction(EPSs, mainly include polysaccharides, proteins, DNA, and lipids), which can attach to almost all surfaces
Bacterial biofilms are a highly structured consortium surrounded by self-secreted extracellular polymeric substancesElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.(EPSs, mainly include polysaccharides, proteins, DNA, and lipids), which can attach to almost all surfaces
200 μL of bacterial culture using Lysogeny broth (LB) medium at a final concentration of 5 × 105 CFU/mL was added into 96-well microplate (Corning, USA), followed by addition of 1 μL of BU dissolved in DMSO at final concentrations of 50, 100, 200, 500, 800, 1000, and 1200 mg/L

Summary

Introduction

(EPSs, mainly include polysaccharides, proteins, DNA, and lipids), which can attach to almost all surfaces. Bacteria in biofilm become more resistant to antibiotics (10– 1000 times) and to host immune defense than those in planktonic state both in vitro and in vivo (Fux et al 2005; Gilbert et al 2002; Høiby et al 2010; Høiby et al 2011). It is estimated that around 80% of microbial infections were associated with biofilm formation (National Institutes of Health 2002), including surface infections of wounds and organs, and serious implanted device-derived secondary infections (Bryers 2008; Francolini and Donelli 2010; Wu et al 2015a). Though biofilm infections are highly recalcitrant to bactericidal agents, planktonic cells derived from biofilm are fully susceptible to antibiotics in most cases (Lewis 2006; Lewis 2010). Antibiofilm agents, if applied as enhancers with antibiotics, may be a promising solution to treat

Methods

Results

Conclusion