{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:21:10Z","timestamp":1786594870842,"version":"build-2736575974"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | NIH | OSC | Common Fund","award":["R01AI141101"],"award-info":[{"award-number":["R01AI141101"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2023,9,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Development of new therapeutics against antibiotic resistant pathogenic bacteria is recognized as a priority across the globe. We have reported using peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) as species-specific antibiotics. The oligo sequences, 11 bases are designed to be complementary to specific essential genes near the Shine-Dalgarno site and inhibit translation. Here, we analyzed target specificity and the impact of genetic mutations on lead PPMOs targeting the\n            <jats:italic>rpsJ<\/jats:italic>\n            or\n            <jats:italic>acpP<\/jats:italic>\n            gene of\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            . Mutants in\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            PAO1 were generated with four, two, or one base-pair mutations within the 11-base target sequence of the\n            <jats:italic>rpsJ<\/jats:italic>\n            gene. All mutants exhibited increased MICs compared to wild-type PAO1 when treated with the RpsJ PPMO, and the increase in the MICs was proportional to the number of base-pair mutations. Among single base-pair mutants, mutations in the middle of the sequence were more impactful than mutations in 5\u2032 or 3\u2032 end of the sequence. The increased MICs shown by the\n            <jats:italic>rpsJ<\/jats:italic>\n            mutants could be reversed by PPMOs designed to target the mutated\n            <jats:italic>rpsJ<\/jats:italic>\n            sequence. BALB\/c mice infected intratracheally with mutants demonstrated increased lung burden when treated with RpsJ PPMO compared to wild-type PAO1-infected mice treated with RpsJ PPMO. Treating mice with a PPMOs designed to specifically target the mutant sequence was more effective against these mutant strains. These experiments confirm target specificity of two lead\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            PPMOs and illustrate one potential mechanism of resistance that could emerge from an antisense approach.\n          <\/jats:p>","DOI":"10.1128\/aac.00245-23","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T13:01:52Z","timestamp":1692795712000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Sequence specificity defines the effectiveness of PPMOs targeting\n            <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5082-7004","authenticated-orcid":true,"given":"A. K.","family":"Nanayakkara","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. A.","family":"Moustafa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children\u2019s Healthcare of Atlanta, Center for Cystic Fibrosis and Airway Diseases Research, Emory University School of Medicine , Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Pifer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. B.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children\u2019s Healthcare of Atlanta, Center for Cystic Fibrosis and Airway Diseases Research, Emory University School of Medicine , Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5101-3106","authenticated-orcid":true,"given":"D. 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P T 40:277\u2013283.","journal-title":"P T"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21697"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3205\/id000040"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0504-3"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.2899"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2015.09.069"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01938-16"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki129"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00099-09"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit460"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/652807"},{"key":"e_1_3_3_16_2","first-page":"109","article-title":"Antibacterial antisense","volume":"7","author":"Geller BL","year":"2005","unstructured":"Geller BL . 2005. 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