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Title page for ETD etd-05152018-122048


Type of Document Dissertation
Author Ackerman, Dorothy LeeAnn
Author's Email Address dorothy.l.ackerman@vanderbilt.edu
URN etd-05152018-122048
Title Human Milk Oligosaccharides as a Defense Against Group B Streptococcus
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
Steven D. Townsend, Ph.D. Committee Chair
Carmelo J. Rizzo, PhD Committee Member
David M. Aronoff, PhD Committee Member
Gary A. Sulikowski, PhD Committee Member
Keywords
  • human milk oligosaccharides
  • HMO
  • Group B Streptococcus
  • GBS
  • antimicrobial
  • antibiofilm
Date of Defense 2018-04-26
Availability restrictone
Abstract
Streptococcus agalactiae (Group B strep, GBS) is a common infant pathogen that causes sepsis and meningitis. Human milk provides nutrition for the developing infant, and breast milk consumption leads to critical modulation of the host immune development, which promotes both tolerance and immunity. This protection is due, in part, to human milk oligosaccharides (HMOs). Minimal research has been done to study the interaction between human milk and GBS. In this work, we describe the ability of HMOs isolated from donor milk to modulate both the proliferation and biofilm production of GBS and affirm the importance of HMOs in infant health. To further probe the individual oligosaccharides responsible for the antimicrobial and anti-biofilm properties of HMOs, we developed a succinct and scalable synthesis of several human milk trisaccharides and unnatural congeners. The synthesis and direct glycosylation of a lactose acceptor with several donors furnished compounds that are or resemble small HMOs. Biological evaluation of these compounds against GBS revealed the antimicrobial and anti-biofilm properties are likely associated with terminally fucosylated and galactosylated species.
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