The trehalose-specific transporter LpqY-SugABC is required for antimicrobial and anti-biofilm activity of trehalose analogues in Mycobacterium smegmatis.

Autor: Wolber JM; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI 48859, United States., Urbanek BL; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI 48859, United States., Meints LM; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI 48859, United States., Piligian BF; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI 48859, United States., Lopez-Casillas IC; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI 48859, United States., Zochowski KM; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI 48859, United States., Woodruff PJ; Department of Chemistry, University of Southern Maine, Portland, ME 04104, United States., Swarts BM; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI 48859, United States. Electronic address: ben.swarts@cmich.edu.
Jazyk: angličtina
Zdroj: Carbohydrate research [Carbohydr Res] 2017 Oct 10; Vol. 450, pp. 60-66. Date of Electronic Publication: 2017 Aug 09.
DOI: 10.1016/j.carres.2017.08.003
Abstrakt: Mycobacteria, including the bacterial pathogen that causes human tuberculosis, possess distinctive pathways for synthesizing and utilizing the non-mammalian disaccharide trehalose. Trehalose metabolism is essential for mycobacterial viability and has been linked to in vitro biofilm formation, which may bear relevance to in vivo drug tolerance. Previous research has shown that some trehalose analogues bearing modifications at the 6-position inhibit growth of various mycobacterial species. In this work, 2-, 5-, and 6-position-modified trehalose analogues were synthesized using our previously reported one-step chemoenzymatic method and shown to inhibit growth and biofilm formation in the two-to three-digit micromolar range in Mycobacterium smegmatis. The trehalose-specific ABC transporter LpqY-SugABC was essential for antimicrobial and anti-biofilm activity, suggesting that inhibition by monosubstituted trehalose analogues requires cellular uptake and does not proceed via direct action on extracellular targets such as antigen 85 acyltransferases or trehalose dimycolate hydrolase. Although the potency of the described compounds in in vitro growth and biofilm assays is moderate, this study reports the first trehalose-based mycobacterial biofilm inhibitors and reinforces the concept of exploiting unique sugar uptake pathways to deliver inhibitors and other chemical cargo to mycobacteria.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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