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Title page for ETD etd-03222019-085659


Type of Document Dissertation
Author Craft, Kelly Marie
URN etd-03222019-085659
Title Human Milk Oligosaccharides as a Defense Against Infectious Diseases
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
Steven D. Townsend, Ph.D. Committee Chair
Brian O. Bachmann, Ph.D. Committee Member
Gary A. Sulikowski, Ph.D. Committee Member
Jennifer A. Gaddy, Ph.D. Committee Member
Keywords
  • Human milk oligosaccharide
  • Infectious diseases
  • Group B Streptococcus
  • Carbohydrate
  • HMO
Date of Defense 2019-03-14
Availability unrestricted
Abstract
The increasing prevalence of antibiotic resistance coupled with a dramatically slowed rate of novel antibiotic discovery has created an environment wherein antimicrobial resistance is one of the most serious threats to human health. To compound this problem, even when antibiotics succeed, they often cause collateral damage to the host microbiome. Thus, there is a growing need to develop not only antimicrobials with unique structures and modes of action but also narrow-spectrum antimicrobials capable of sparing commensal species. With its numerous protective factors, human milk is a potential source of such compounds. Principally, human milk contains human milk oligosaccharides (HMOs) which are well known for their abilities to protect infants from infection and promote proper development. Given these characteristics, we hypothesized that HMOs could serve as antimicrobial and antivirulence agents against the important neonate pathogen Group B Streptococcus (GBS). Our studies revealed that both heterogenous HMO extracts and numerous single-entity HMOs possess strong antimicrobial and antibiofilm activity against GBS. Moreover, we demonstrated that HMOs potentiate the activity of several ribosome-targeting antibiotics by compromising GBS cellular integrity. Extending our studies beyond GBS, we demonstrated that heterogenous HMOs possess strong antibiofilm activity against Staphylococcus aureus and weak antimicrobial activity against Acinetobacter baumannii. Furthermore, we found that HMOs potentiate the activity of aminoglycosides against both S. aureus and A. baumannii.
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