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1-Amino-2′-fucosyllactose inhibits biofilm formation by Streptococcus agalactiae

The Journal of Antibiotics volume 72, pages 507–512 (2019)Cite this article

Abstract

2′-Fucosyllactose (2′-FL) is a ubiquitous oligosaccharide in human milk. Importantly, this carbohydrate promotes the growth of several strains of Bifidobacteria, a class of beneficial gut commensal, and inhibits epithelial binding of pathogens. In light of these protective effects, we elected to evaluate the potential of 2′-FL to serve as an antibacterial agent against Group B Streptococcus (GBS). While 2′-FL was devoid of any substantial antimicrobial or antibiofilm activity, conversion of 2′-FL to its reducing end β-amine provided a novel antibiofilm compound.

Biofilms consist of an organized population of bacteria that adhere to both abiotic and biotic surfaces. These bacteria are encapsulated by an extracellular polymeric matrix [1, 2]. At the molecular level, this matrix consists of an extracellular polymeric substance (EPS) composed primarily of DNA, polysaccharides, and an assortment of proteins. The EPS is critical to the structural integrity of biofilms, the ability of biofilms to adhere to different surfaces, and the ability of bacteria to adhere to and communicate with one another [3]. Biofilms are a major concern to human health as it is estimated that they are involved in upwards of 80% of microbial infections [1]. Indeed, the majority of bacterial pathogens use biofilm as a key virulence factor to enhance their pathogenicity and enable their survival in a hostile host environment [4,5,6]. In particular, one hallmark feature of bacteria in the biofilm state is an increased resistance to antibiotics [1, 2, 7, 8]. Remarkably, these species are up to 1000-fold more resistant to antimicrobial agents than bacteria in the planktonic state [1, 8].

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Acknowledgements

This material is based upon work supported by the National Science Foundation under Grant No. [1847804]. This work was also supported by Vanderbilt University, the Vanderbilt Microbiome Initiative (VMI), the Department of Pediatrics at Vanderbilt University Medical Center, and Prolacta Bioscience for S.D.T. K.M.C. was supported by the Vanderbilt Chemical Biology Interface (CBI) training program (T32 GM065086), the Vanderbilt Pre3 Initiative (travel grant), and the Mitchum E. Warren, Jr. Graduate Research Fellowship. Prof. Jennifer Gaddy is acknowledged for use of her facilities. Prof. Shannon Manning at Michigan State University is acknowledged for generously providing clinical strains of GBS (GBS590 and GBS2). Harrison Thomas is acknowledged for his assistance with the viability and biofilm assays. Ryan Doster is acknowledged for discussions regarding experimental design. Jacky Lu is acknowledged for his assistance with bacterial culturing.

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Authors and Affiliations

  1. Department of Chemistry, Vanderbilt University, 7330 Stevenson Center, Nashville, TN, 37235, USA

    Kelly M. Craft & Steven D. Townsend

  2. Institute of Chemical Biology, Vanderbilt University, 896 Preston Research Building, Nashville, TN, 37232, USA

    Steven D. Townsend

  3. Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University, Medical Center North A-5302, 1161 21st Ave South, Nashville, TN, 37232, USA

    Steven D. Townsend

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  1. Kelly M. Craft
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Correspondence to Steven D. Townsend.

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Dedication: This manuscript is dedicated to Professor Samuel J. Danishefsky in recognition of his manifold contributions to chemical synthesis, bioorganic chemistry, and the thoughtful mentorship of organic chemists.

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Craft, K.M., Townsend, S.D. 1-Amino-2′-fucosyllactose inhibits biofilm formation by Streptococcus agalactiae. J Antibiot 72, 507–512 (2019). https://doi.org/10.1038/s41429-019-0151-6

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