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The minimum inhibitory concentration (MIC) of 600\u2005Da BPEI and PEGylated 600\u2005Da BPEI (PEG\u2010BPEI) in the wild\u2010type PAO1 strain is 16\u2005\u03bcg\/ml while, after 15 serial passages, the MIC increased to 1024\u2005\u03bcg\/mL. An additional 15 rounds of serial passage in the absence of BPEI or PEG\u2010BPEI did not change the 1024\u2005\u03bcg\/mL MIC. Gentamicin, Neomycin, and Tobramycin, cationic antibiotics that inhibit protein synthesis, have a 16\u201332 fold reduction of MIC values in PEG350\u2010BPEI resistant strains, suggesting increased permeation. The influx of these antibiotics occurs using a self\u2010mediated uptake mechanism, suggesting changes to the outer membrane Data show that resistance causes changes in genes related to outer membrane lipopolysaccharide (LPS) assembly. Mutations were noted in the gene coding for the polymerase Wzy that participates in the assembly of the O\u2010antigen region. Other mutations were noted with wbpE and wbpI of the Wbp pathway responsible for the enzymatic synthesis of ManNAc(3NAc)A in the LPS of <jats:italic>P. aeruginosa<\/jats:italic>. These changes suggest that an altered gene product could lead to PEG\u2010BPEI resistance. Nevertheless, the increased susceptibility to aminoglycosides could prevent the emergence of PEG\u2010BPEI resistant bacterial populations.<\/jats:p>","DOI":"10.1002\/cmdc.202300689","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T22:24:01Z","timestamp":1716935041000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acquisition of Resistance to PEGylated Branched Polyethylenimine Increases <i>Pseudomonas Aeruginosa<\/i> Susceptibility to Aminoglycosides"],"prefix":"10.1002","volume":"19","author":[{"given":"William","family":"Best","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73069"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Ferrell","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73069"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Boris","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73069"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neda","family":"Heydarian","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73069"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Panlilio","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73069"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-405X","authenticated-orcid":false,"given":"Charles V.","family":"Rice","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma  101 Stephenson Parkway Norman OK 73069"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,15]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"\u00a0"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.076034-0"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2015.24.8.366"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000539"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.12426"},{"key":"e_1_2_8_6_1","unstructured":"\u00a0"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(00)01259-4"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/sur.2009.024"},{"key":"e_1_2_8_9_1","unstructured":"\u00a0"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00112"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw353"},{"key":"e_1_2_8_12_1","unstructured":"\u00a0"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2009.00543.x"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms5010009"},{"key":"e_1_2_8_15_2","doi-asserted-by":"crossref","unstructured":"H.\u2005W. 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