Synthesis of Ribitol Phosphate based Wall Teichoic acids

Antibiotic resistance, caused by widespread use of antibiotics, leads to bacterial infections that are difficult, if not impossible, to treat and is a major worldwide health concern.

Author: Ali, S.
Date: 10 February 2022
Links: Thesis in Leiden Repository

Antibiotic resistance, caused by widespread use of antibiotics, leads to bacterial infections that are difficult, if not impossible, to treat and is a major worldwide health concern. Currently Methicillin-resistant Staphylococcus aureus (MRSA) is the most commonly identified antibiotic-resistant pathogen in clinical medicine worldwide. The spread of MRSA highlights the urgent need for alternative therapies, such as vaccination.Wall teichoic acids (WTAs), prime constituents of the Gram-positive cell wall, can function as effective antigenic epitopes and are therefore promising candidates for the development of a conjugate vaccine against S. aureus infections. WTAs are anionic poly-ribitol phosphate (RboP) chains attached to the peptidoglycan and they have a fundamentol role in the physiology in the bacteria.Since isolation from the bacteria of WTAs leads to heterogenous mixtures of fragments and bacterial contaminations, organic synthesis is the method of choice to generate WTA-fragments with pre-defined substitution patterns in higher purity and in larger amounts, allowing detailed immunological studies that can aid in future vaccine development.This Thesis presents methods to synthesize various WTA-fragments from Staphylococcus aureus and Enterococcus faecalis and their applications.