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Capsule is important for the pathogenesis of<jats:italic>Klebsiella<\/jats:italic>in systemic infection, but its role in gut colonisation is not well understood. By generating \u0394<jats:italic>wcaJ<\/jats:italic>, \u0394<jats:italic>wza<\/jats:italic>and \u0394<jats:italic>wzy<\/jats:italic>capsule\u2010null mutants in a prototypical K1 hypervirulent isolate, we show that inactivation of<jats:italic>wza<\/jats:italic>(capsule exportase) and<jats:italic>wzy<\/jats:italic>(capsule polymerase) confer cell envelope defects in addition to capsule loss, making them susceptible to bile salts and detergent stress. Bile salt resistance is restored when the initial glycosyltransferase<jats:italic>wcaJ<\/jats:italic>was inactivated together with<jats:italic>wzy<\/jats:italic>, indicating that build\u2010up of capsule intermediates contribute to cell envelope defects. Mouse gut colonisation competition assays show that the capsule and its regulator RmpA were not required for hvKP to persist in the gut, although initial colonisation was decreased in the mutants. Both \u0394<jats:italic>rmpA<\/jats:italic>and \u0394<jats:italic>wcaJ<\/jats:italic>mutants gradually outcompeted the wild type in the gut, whereas \u0394<jats:italic>wza<\/jats:italic>and \u0394<jats:italic>wzy<\/jats:italic>mutants were less fit than wild type. Together, our results advise caution in using the right capsule\u2010null mutant for determination of capsule's role in bacterial pathogenesis. With the use of \u0394<jats:italic>wcaJ<\/jats:italic>mutant, we found that although the capsule is important for bacterial survival outside the gut environment, it imposes a fitness cost in the gut.<\/jats:p>","DOI":"10.1111\/mmi.14447","type":"journal-article","created":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T04:27:13Z","timestamp":1578457633000},"page":"889-905","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Cell envelope defects of different capsule\u2010null mutants in K1 hypervirulent<i>Klebsiella pneumoniae<\/i>can affect bacterial pathogenesis"],"prefix":"10.1111","volume":"113","author":[{"given":"Yi Han","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Biochemistry Yong Loo Lin School of Medicine, National University of Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Yong Loo Lin School of Medicine, National University of Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson H. 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