{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:38:01Z","timestamp":1791326281712,"version":"4.3.1"},"reference-count":41,"publisher":"Microbiology Society","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,4,1]]},"abstract":"<jats:p>Actinomycete bacteria use polyprenol phosphate mannose as a lipid linked sugar donor for extra-cytoplasmic glycosyl transferases that transfer mannose to cell envelope polymers, including glycoproteins and glycolipids. We showed recently that strains of <jats:italic>Streptomyces coelicolor<\/jats:italic> with mutations in the gene <jats:italic>ppm1<\/jats:italic> encoding polyprenol phosphate mannose synthase were both resistant to phage \u03c6C31 and have greatly increased susceptibility to antibiotics that mostly act on cell wall biogenesis. Here we show that mutations in the genes encoding enzymes that act upstream of Ppm1 in the polyprenol phosphate mannose synthesis pathway can also confer phage resistance and antibiotic hyper-susceptibility. GDP-mannose is a substrate for Ppm1 and is synthesised by GDP-mannose pyrophosphorylase (GMP; ManC) which uses GTP and mannose-1-phosphate as substrates. Phosphomannomutase (PMM; ManB) converts mannose-6-phosphate to mannose-1-phosphate. <jats:italic>S. coelicolor<\/jats:italic> strains with knocked down GMP activity or with a mutation in <jats:italic>sco3028<\/jats:italic> encoding PMM acquire phenotypes that resemble those of the <jats:italic>ppm1<\/jats:italic>\n                  <jats:sup>-<\/jats:sup> mutants i.e. \u03c6C31 resistant and susceptible to antibiotics. Differences in the phenotypes of the strains were observed, however. While the <jats:italic>ppm1<\/jats:italic>\n                  <jats:sup>-<\/jats:sup> strains have a small colony phenotype, the <jats:italic>sco3028\u200a<\/jats:italic>::\u200aTn<jats:italic>5062<\/jats:italic> mutants had an extremely small colony phenotype indicative of an even greater growth defect. Moreover we were unable to generate a strain in which GMP activity encoded by <jats:italic>sco3039<\/jats:italic> and <jats:italic>sco4238<\/jats:italic> is completely knocked out, indicating that GMP is also an important enzyme for growth. Possibly GDP-mannose is at a metabolic branch point that supplies alternative nucleotide sugar donors.<\/jats:p>","DOI":"10.1099\/mic.0.000636","type":"journal-article","created":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T15:12:39Z","timestamp":1519917159000},"page":"614-624","source":"Crossref","is-referenced-by-count":19,"title":["Disruption of the GDP-mannose synthesis pathway in Streptomyces coelicolor results in antibiotic hyper-susceptible phenotypes"],"prefix":"10.1099","volume":"164","author":[{"given":"Robert","family":"Howlett","sequence":"first","affiliation":[{"name":"Department of Biology, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri","family":"Anttonen","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Read","sequence":"additional","affiliation":[{"name":"Department of Biology, University of York, York, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret C. 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