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We previously identified the UDP\u2010<jats:italic>N<\/jats:italic>\u2010acetyl\u2010<jats:sc>d<\/jats:sc>\u2010galactosaminuronic acid (UDP\u2010GalNAcA) biosynthesis genes, <jats:italic>gna<\/jats:italic>\u2010<jats:italic>gne2<\/jats:italic>, as being critical for survival <jats:italic>in vivo<\/jats:italic>. Herein, we demonstrate that Gna\u2010Gne2 are part of a complex network connecting <jats:italic>in vivo<\/jats:italic> fitness, cell envelope homeostasis and resistance to antibiotics. The \u2206<jats:italic>gna<\/jats:italic>\u2010<jats:italic>gne2<\/jats:italic> mutant exhibits a severe fitness defect during bloodstream infection. Capsule production is abolished in the mutant strain, which is concomitant with its inability to survive in human serum. In addition, the \u2206<jats:italic>gna<\/jats:italic>\u2010<jats:italic>gne2<\/jats:italic> mutant was more susceptible to vancomycin and unable to grow on MacConkey plates, indicating an alteration in cell envelope integrity. Analysis of lipid A by mass spectrometry showed that the hexa\u2010 and hepta\u2010acylated species were affected in the <jats:italic>gna<\/jats:italic>\u2010<jats:italic>gne2<\/jats:italic> mutant. Finally, the \u2206<jats:italic>gna<\/jats:italic>\u2010<jats:italic>gne2<\/jats:italic> mutant was more susceptible to several classes of antibiotics. Together, this study demonstrates the importance of UDP\u2010GalNAcA in the pathobiology of <jats:italic>A<\/jats:italic>. <jats:italic>baumannii<\/jats:italic>. By interrupting its biosynthesis, we showed that this molecule plays a critical role in capsule biosynthesis and maintaining the cell envelope homeostasis.<\/jats:p>","DOI":"10.1111\/mmi.14407","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T01:25:15Z","timestamp":1572830715000},"page":"153-172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The UDP\u2010GalNAcA biosynthesis genes <i>gna<\/i>\u2010<i>gne2<\/i> are required to maintain cell envelope integrity and <i>in vivo<\/i> fitness in multi\u2010drug resistant <i>Acinetobacter baumannii<\/i>"],"prefix":"10.1111","volume":"113","author":[{"given":"S\u00e9bastien","family":"Cr\u00e9pin","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth N.","family":"Ottosen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney E.","family":"Chandler","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis School of Dentistry University of Maryland Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Sintsova","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert K.","family":"Ernst","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis School of Dentistry University of Maryland Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9195-7665","authenticated-orcid":false,"given":"Harry L. 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