Tuberculosis is the leading infectious cause of mortality worldwide. The global epidemic, caused by Mycobacterium tuberculosis, has prompted renewed interest in the development of novel vaccines for disease prevention and control. The cell envelope of M. tuberculosis is decorated with an assortment of glycan structures, including glycolipids, that are involved in disease pathogenesis. Phenolic glycolipids and the structurally related para-hydroxybenzoic acid derivatives display potent immunomodulatory activities and have particular relevance for both understanding the interaction of the bacterium with the host immune system and also in the design of new vaccine and therapeutic candidates. Interest in glycobiology has grown exponentially over the past decade, with advancements paving the way for effective carbohydrate based vaccines. This review highlights recent advances in our understanding of phenolic glycans, including their biosynthesis and role as virulence factors in M. tuberculosis. Recent chemical synthesis approaches and biochemical analysis of synthetic glycans and their conjugates have led to fundamental insights into their roles in host-pathogen interactions. The applications of these synthetic glycans as potential vaccine candidates are discussed.
Carbon nano-onions (CNOs) possess favorable properties that make them suitable for biomedical applications, including their small size, ready surface modification, and good biocompatibility. Here, we report the covalent immobilization of a synthetic glycopeptide and the protein bovine serum albumin (BSA) onto the surface of carbon nano-onions using the maleimide–thiol “addition reaction”. The glycopeptide and BSA are readily transported inside different cell lines, together with carbon nano-onions, through the endocytosis pathway. Our results show that carbon nano-onions are excellent scaffolds for glycopeptides and proteins immobilization and act as intracellular carriers for these biomolecules. These findings open new perspectives in the application of carbon nano-onions as intracellular transporters in diverse biomedical applications.
Macrophages are key immune cells for combatting Mycobacterium tuberculosis. However, M. tuberculosis possesses means to evade macrophage bactericidal responses by, for instance, secretion of the immunomodulatory para-hydroxybenzoic acid derivatives (pHBADs). While these molecules have been implicated in inhibiting macrophage responses in an acute context, little is known about their ability to reprogram macrophages via induction of long-term innate memory. Since innate memory has been highlighted as a promising strategy to augment bactericidal immune responses against M. tuberculosis, investigating corresponding immune evasion mechanisms is highly relevant. Our results reveal for the first time that pHBAD I and related molecules (unmethylated pHBAD I and the hexose l-rhamnose) reduce macrophage bactericidal mechanisms in both the short- and the long-term. Moreover, we demonstrate how methyl-p-anisate hinders bactericidal responses soon after exposure yet results in enhanced pro-inflammatory responses in the long-term. This work highlights new roles for these compounds in M. tuberculosis pathogenesis.
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