Pathogens including viruses, bacteria, fungi, and parasites continue to shape our lives in profound ways every day. As we have learned to live in parallel with pathogens, we have gained a better understanding of the rules of engagement for how they bind, adhere, and invade host cells. One such mechanism involves the exploitation of host cell surface glycans for attachment/adhesion, one of the first steps of infection. This knowledge has led to the development of glycan-based diagnostics and therapeutics for the treatment and prevention of infection. One class of compounds that has become increasingly important are the glycopolymers. Glycopolymers are macromolecules composed of a synthetic scaffold presenting carbohydrates as side chain motifs. Glycopolymers are particularly attractive because their properties can be tuned by careful choice of the scaffold, carbohydrate/glycan, and overall presentation. In this review, we highlight studies over the past ten years that have examined the role of glycopolymers in pathogen adhesion and host cell infection, biofilm formation and removal, and drug delivery with the aim of examining the direct effects of these macromolecules on pathogen engagement. In addition, we also examine the role of glycopolymers as diagnostics for the detection and monitoring of pathogens.
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Nat Commun
January 2025
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Wall teichoic acids (WTAs) from the major Gram-positive foodborne pathogen Listeria monocytogenes are peptidoglycan-associated glycopolymers decorated by monosaccharides that, while not essential for bacterial growth, are required for bacterial virulence and resistance to antimicrobials. Here we report the structure and function of a bacterial WTAs rhamnosyltransferase, RmlT, strictly required for L. monocytogenes WTAs rhamnosylation.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Mucins are key components of innate immune defense and possess remarkable abilities to manage pathogenic microbes while supporting beneficial ones and maintaining microbial homeostasis at mucosal surfaces. Their unique properties have garnered significant interest in developing mucin-inspired materials as novel therapeutic strategies for selectively controlling pathogens without disrupting the overall microbial ecology. However, natural mucin production is challenging to scale, driving the need for simpler materials that reproduce mucin's bioactivity.
View Article and Find Full Text PDFmBio
January 2025
Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
is among the leading causes of hospital-acquired infections. Critical to biology and pathogenesis are the cell wall-anchored glycopolymers wall teichoic acids (WTA). Approximately one-third of isolates decorates WTA with a mixture of α1,4- and β1,4--acetylglucosamine (GlcNAc), which requires the dedicated glycosyltransferases TarM and TarS, respectively.
View Article and Find Full Text PDFbioRxiv
October 2024
Center for Radiological Research, Columbia University Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
High-dose radiation exposure results in gastrointestinal (GI) acute radiation syndrome identified by the destruction of mucosal layer, intestinal epithelial barrier dysfunction, and aberrant inflammatory responses. In addition, radiation causes gut microbiome dysbiosis characterized by diminished microbial diversity, reduction in the abundance of beneficial commensal bacteria, and the spread of bacterial pathogens that trigger the recruitment of immune cells and the production of pro-inflammatory factors that lead to further GI tissue damage. Currently, there are no FDA-approved countermeasures that can treat radiation-induced GI injury.
View Article and Find Full Text PDFBiomacromolecules
November 2024
Department of Chemistry, Durham University, Durham DH1 3LE, U.K.
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