{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:56:25Z","timestamp":1787756185312,"version":"build-2784847793"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T00:00:00Z","timestamp":1555027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004331","name":"Johnson and Johnson","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["MicrobiologyOpen"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>In the lungs of cystic fibrosis patients, <jats:italic>Pseudomonas aeruginosa<\/jats:italic> is exposed to a myriad of antibiotics leading to alterations in antibiotic susceptibility. This study identifies mutations resulting in hypersusceptibility in isogenic mutants of a <jats:italic>P. aeruginosa<\/jats:italic> clinical isolate, PA34.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PA34 was exposed to subinhibitory concentrations of doripenem or meropenem during growth to mid\u2010log phase. Antibiotic susceptibility of surviving colonies was determined by agar dilution. Two carbapenem\u2010resistant colonies hypersusceptible to non\u2010carbapenem antibiotics were selected for further analysis. Antibiotic resistance gene expression was evaluated by RT\u2010rtPCR and OprD production by SDS\u2010PAGE. PA34 and isogenic mutants were evaluated with whole genome sequencing. Sequence variants were confirmed by Sanger sequencing, and cognate genes in eight carbapenem\u2010resistant clinical isolates hypersusceptible to non\u2010carbapenem antibiotics were sequenced. Lipopolysaccharide preparations of PA34 and hypersusceptible mutants were evaluated with ProQ\u2010Emerald stain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Isogenic mutants showed 4\u2010 to 8\u2010fold MIC increase for imipenem, meropenem, and doripenem. However, they were hypersusceptible (\u22654\u2010fold MIC decrease) to aminoglycosides, fluoroquinolones, and non\u2010carbapenem \u03b2\u2010lactams. Expression of <jats:italic>ampC<\/jats:italic> or <jats:italic>mex<\/jats:italic>\u2010<jats:italic>opr<\/jats:italic> efflux pumps was unchanged, but OprD production was decreased. Mutations causing Q86H AlgU and G77C LptG amino acid substitutions and nonsense mutations within OprD were observed in both mutants. Lipopolysaccharide modifications were observed between isogenic mutants and PA34. Non\u2010synonymous mutations in LptF or LptG were observed in 6\/8 hypersusceptible clinical isolates resistant to carbapenem antibiotics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Evaluation of hypersusceptible mutants identified the association between <jats:italic>lptG<\/jats:italic> and a hypersusceptible phenotype. Modifications in lipopolysaccharide profiles suggests LptG modification interferes with lipopolysaccharide transport and contributes to hypersusceptibility.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mbo3.844","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T11:39:31Z","timestamp":1555069171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<i>lptG<\/i> contributes to changes in membrane permeability and the emergence of multidrug hypersusceptibility in a cystic fibrosis isolate of <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1002","volume":"8","author":[{"given":"Lucas B.","family":"Harrison","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randal C.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baha","family":"Abdalhamid","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Selmecki","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6558-2465","authenticated-orcid":false,"given":"Nancy D.","family":"Hanson","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology Creighton University Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00257-10"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.21.2.299"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01747-15"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.2012.0021"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu291"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00222-08"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02676-15"},{"key":"e_1_2_10_9_1","unstructured":"Clinical and Laboratory Standards Institute(2012).Performance standards for antimicrobial susceptibility testing: Twenty\u2010second informational supplement. 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