{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:37Z","timestamp":1787028577540,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["2023-NS-004-02"],"award-info":[{"award-number":["2023-NS-004-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acinetobacter baumannii represents a critical-priority organism due to its multidrug resistance. The emergence of carbapenem-resistant strains poses a major clinical challenge, underscoring the urgent need for novel antibacterial agents with alternative mechanisms. As peptide nucleic acids (PNAs) have recently gained attention as antisense therapeutics, we aimed to validate their potential as novel antimicrobial strategies against multidrug-resistant A. baumannii. We synthesized a cell-penetrating peptide (CPP)\u2013PNA conjugate targeting pdxA, an essential gene involved in vitamin B6 biosynthesis. Among several candidate genes tested, the pdxA-targeting PNA exhibited the strongest inhibitory activity, achieving complete growth suppression of A. baumannii at 1.56 \u03bcM. Although quantitative real-time polymerase chain reaction did not reveal significant reductions in pdxA transcript levels, ELISA quantification revealed an approximately 80% reduction in intracellular vitamin B6, indicating translational inhibition rather than mRNA degradation. The pdxA-targeting CPP\u2013PNA showed negligible activity against other Gram-negative or Gram-positive species, indicating high target specificity; no detectable cytotoxicity in human cells was observed even at relatively high concentrations. CPP\u2013PNA conjugates targeting pdxA interfere with vitamin B6 biosynthesis, leading to growth inhibition of A. baumannii. These findings support PNA as a promising antisense antimicrobial platform that inhibits multidrug-resistant A. baumannii by blocking vitamin B6 biosynthesis.<\/jats:p>","DOI":"10.3390\/ijms27020584","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T15:09:36Z","timestamp":1767712176000},"page":"584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CPP-PNA Conjugate-Mediated Inhibition of pdxA Gene Impairs Vitamin B6 Biosynthesis and Growth in Acinetobacter baumannii"],"prefix":"10.3390","volume":"27","author":[{"given":"Wook-Jong","family":"Jeon","sequence":"first","affiliation":[{"name":"Division of Antimicrobial Resistance Research, National Institute of Health, Korea Disease Control and Prevention Agency, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Hui","family":"Seo","sequence":"additional","affiliation":[{"name":"Division of Antimicrobial Resistance Research, National Institute of Health, Korea Disease Control and Prevention Agency, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoo Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Antimicrobial Resistance Research, National Institute of Health, Korea Disease Control and Prevention Agency, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-mee","family":"Bae","sequence":"additional","affiliation":[{"name":"Division of Antimicrobial Resistance Research, National Institute of Health, Korea Disease Control and Prevention Agency, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1244-201X","authenticated-orcid":false,"given":"Dong Chan","family":"Moon","sequence":"additional","affiliation":[{"name":"Division of Antimicrobial Resistance Research, National Institute of Health, Korea Disease Control and Prevention Agency, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Chungcheongbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1586\/14787210.2015.1025055","article-title":"Community-acquired Acinetobacter baumannii: Clinical characteristics, epidemiology and pathogenesis","volume":"13","author":"Dexter","year":"2015","journal-title":"Expert. 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