{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T09:46:56Z","timestamp":1766396816147,"version":"3.48.0"},"reference-count":147,"publisher":"Royal Society of Chemistry","isbn-type":[{"value":"9781837675494","type":"print"},{"value":"9781837675494","type":"print"},{"value":"9781837676118","type":"electronic"},{"value":"9781837676101","type":"electronic"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,22]]},"abstract":"<jats:p>The genus Mycobacterium comprises numerous species, including major human pathogens responsible for two diseases \u2013 tuberculosis and leprosy \u2013 that have afflicted humanity for millennia. Other Mycobacterium species are known to cause chronic lung infections, some of which spread through modern water distribution systems that they can colonize. Mycobacteria have a distinctive cell envelope that comprises a complex matrix of lipids, sugars, and lipoglycans, and which forms a formidable barrier against environmental stress and host immune responses, contributing to their resilience. They also possess two types of intracellular polymethylated polysaccharides, 6-O-methylglucose lipopolysaccharide (MGLP) and 3-O-methylmannose polysaccharide (MMP), which influence the synthesis of fatty acid precursors of envelope components. While in vitro studies have demonstrated their interactions with fatty acids and regulatory effects on fatty acid synthase activity, the precise in vivo functions remain elusive. MGLP has been implicated in heat stress adaptation, whereas MMP may play a role in cold stress responses. Although MGLP biosynthetic genes are conserved across mycobacterial genomes, a MMP biosynthetic gene cluster is absent in the important pathogens M. tuberculosis, M. leprae, and M. abscessus. MGLP biosynthesis follows a de novo pathway beginning with the glycoside glucosylglycerate (GG) and involving various gene clusters, whereas MMP biosynthesis seems to be governed by a single gene cluster encoding an MMP hydrolase that facilitates a self-recycling mechanism, generating oligomannoside primers for synthesis of new MMP. Despite gaps in our understanding of their physiological roles, particularly their impact on fatty acid metabolism and envelope integrity, and their restricted distribution, the enzymes in these pathways may represent promising targets for novel therapeutic interventions against mycobacterial infections, which remain pressing global health challenges.<\/jats:p>","DOI":"10.1039\/9781837676101-00118","type":"book-chapter","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T09:40:07Z","timestamp":1766396407000},"page":"118-153","source":"Crossref","is-referenced-by-count":0,"title":["Mycobacterial pathways from simple glycosides to fatty acid-sheltering polymethylated polysaccharides"],"prefix":"10.1039","author":[{"given":"Ana","family":"Maranha","sequence":"first","affiliation":[{"name":"aCenter for Neuroscience and Cell Biology (CNC-UC), University of Coimbra, Portugal"},{"name":"bCentre for Innovative Biomedicine & Biotechnology (CIBB), University of Coimbra, Portugal"}]},{"given":"Nuno","family":"Empadinhas","sequence":"additional","affiliation":[{"name":"aCenter for Neuroscience and Cell Biology (CNC-UC), University of Coimbra, Portugal"},{"name":"bCentre for Innovative Biomedicine & Biotechnology (CIBB), University of Coimbra, Portugal nuno.empadinhas@uc.pt"}]}],"member":"292","reference":[{"key":"2025122204395663400_BK9781837675494-00118-cit1","volume-title":"Global tuberculosis report","author":"WHO","year":"2023"},{"key":"2025122204395663400_BK9781837675494-00118-cit2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ijid.2016.11.007","article-title":"Tuberculosis eradication versus control","volume":"56","author":"Schito","year":"2017","journal-title":"Int. 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