{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:23:22Z","timestamp":1780431802781,"version":"3.54.1"},"reference-count":80,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R00HL143440"],"award-info":[{"award-number":["R00HL143440"]}]},{"name":"HHS | National Institutes of Health","award":["R01GM123251"],"award-info":[{"award-number":["R01GM123251"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,3,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Acinetobacter baumannii<\/jats:italic>\n              is a Gram-negative bacterial pathogen that poses a major health concern due to increasing multidrug resistance. The Gram-negative cell envelope is a key barrier to antimicrobial entry and includes an inner and outer membrane. The maintenance of lipid asymmetry (Mla) system is the main homeostatic mechanism by which Gram-negative bacteria maintain outer membrane asymmetry. Loss of the Mla system in\n              <jats:italic>A. baumannii<\/jats:italic>\n              results in attenuated virulence and increased susceptibility to membrane stressors and some antibiotics. We recently reported two strain variants of the\n              <jats:italic>A. baumannii<\/jats:italic>\n              type strain ATCC 17978: 17978VU and 17978UN. Here, \u2206\n              <jats:italic>mlaF<\/jats:italic>\n              mutants in the two ATCC 17978 strains display different phenotypes for membrane stress resistance, antibiotic resistance, and pathogenicity in a murine pneumonia model. Although allele differences in\n              <jats:italic>obgE<\/jats:italic>\n              were previously reported to synergize with \u2206\n              <jats:italic>mlaF<\/jats:italic>\n              to affect growth and stringent response,\n              <jats:italic>obgE<\/jats:italic>\n              alleles do not affect membrane stress resistance. Instead, a single-nucleotide polymorphism (SNP) in the essential gene encoding undecaprenyl pyrophosphate (Und-PP) synthase,\n              <jats:italic>uppS<\/jats:italic>\n              , results in decreased enzymatic rate and decrease in total Und-P levels in 17978UN compared to 17978VU. The UppS\n              <jats:sup>UN<\/jats:sup>\n              variant synergizes with \u2206\n              <jats:italic>mlaF<\/jats:italic>\n              to reduce capsule and lipooligosaccharide (LOS) levels, increase susceptibility to membrane stress and antibiotics, and reduce persistence in a mouse lung infection. Und-P is a lipid glycan carrier required for the biosynthesis of\n              <jats:italic>A. baumannii<\/jats:italic>\n              capsule, cell wall, and glycoproteins. These findings uncover synergy between Und-P and the Mla system in maintaining the\n              <jats:italic>A. baumannii<\/jats:italic>\n              cell envelope and antibiotic resistance.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                is a critical threat to global public health due to its multidrug resistance and persistence in hospital settings. Therefore, novel therapeutic approaches are urgently needed. We report that a defective undecaprenyl pyrophosphate synthase (UppS) paired with a perturbed Mla system leads to synthetically sick cells that are more susceptible to clinically relevant antibiotics and show reduced virulence in a lung infection model. These results suggest that targeting UppS or undecaprenyl species and the Mla system may resensitize\n                <jats:italic>A. baumannii<\/jats:italic>\n                to antibiotics in combination therapies. This work uncovers a previously unknown synergistic relationship in cellular envelope homeostasis that could be leveraged for use in combination therapy against\n                <jats:italic>A. baumannii<\/jats:italic>\n                .\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/mbio.02804-23","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T20:40:10Z","timestamp":1708116010000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Genetic synergy between\n            <i>Acinetobacter baumannii<\/i>\n            undecaprenyl phosphate biosynthesis and the Mla system impacts cell envelope and antimicrobial resistance"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2046-7049","authenticated-orcid":false,"given":"Hannah 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry M.","family":"Troutman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of North Carolina Charlotte, Charlotte, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7458-6129","authenticated-orcid":true,"given":"Lauren D.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Illinois Chicago, Chicago, Illinois, 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