Synthesis of bioorthogonal muramyl glycans that illuminate and track bacterial peptidoglycan
Date
2019
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Bacterial peptidoglycan (PG) is one of the essential polymers for life. This intricate network of glycans and peptides has an inherent ability to protect both humans and bacterial cells by serving as a target for antibacterial reagents and a regulator for innate immune processing of a healthy microbiome. Details surrounding the immunostimulatory properties of PG fragments that contain a key component of this polymer, the monomeric unit N-acetyl muramic acid (NAM), are not understood, leaving questions surrounding how the innate immune system recognizes and responds selectively to pathogen particles unanswered. In this thesis, fundamental methodology was developed to incorporate NAM based chemical probes into the bacterial peptidoglycan via biochemical pathways of commensal and pathogenic bacterial cells. This methodology permitted the bacterial peptidoglycan to be selectively illuminated and subsequent processing by innate immune cells could be tracked. These tools are incredibly valuable to the fields of microbiology and immunology. In showcase experiments the methodology was used to demonstrate that different bacteria can produce their own unique peptidoglycan fragmentation patterns, allowing a molecular signature for each bacterium to be encoded into the innate immune system. This information is critical for selective antibacterial therapeutic design and will allow direct manipulation of host - microbiome interactions at the bacterial peptidoglycan level.
Description
At the request of the author or degree granting institution, this graduate work is not available to view or purchase until August 31 2027."--ProQuest abstract/details page.
Keywords
Bacteria, Bioorthogonal, Innate immunity, Peptidoglycan, Bacterial peptidoglycan