{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T03:31:58Z","timestamp":1768879918356,"version":"3.49.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Previously, we identified that a cyclic hexapeptide AOA-2 inhibited the interaction of Gram-negative bacilli (GNB) like <jats:italic>Acinetobacter baumannii<\/jats:italic>, <jats:italic>Pseudomonas aeruginosa<\/jats:italic>, and <jats:italic>Escherichia coli<\/jats:italic> to host cells thereby preventing the development of infection <jats:italic>in vitro<\/jats:italic> and in a murine sepsis peritoneal model. In this work, we aimed to evaluate <jats:italic>in vitro<\/jats:italic> a library of AOA-2 derivatives in order to improve the effect of AOA-2 against GNB infections. Ten AOA-2 derivatives were synthetized for the <jats:italic>in vitro<\/jats:italic> assays. Their toxicities to human lung epithelial cells (A549 cells) for 24 h were evaluated by determining the A549 cells viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of these peptide derivatives and AOA-2 at 250, 125, 62.5, and 31.25 \u03bcg\/mL on the attachment of <jats:italic>A. baumannii<\/jats:italic> ATCC 17978, <jats:italic>P. aeruginosa<\/jats:italic> PAO1 and <jats:italic>E. coli<\/jats:italic> ATCC 25922 strains to A549 cells was characterized by adherence and viability assays. None of the 10 derivatives showed toxicity to A549 cells. RW01 and RW06 have reduced more the adherence of ATCC 17978, PAO1 and ATCC 2599 strains to A549 cells when compared with the original compound AOA-2. Moreover, both peptides have increased slightly the viability of infected A549 cells by PAO1 and ATCC 25922 than those observed with AOA-2. Finally, RW01 and RW06 have potentiated the activity of colistin against ATCC 17978 strain in the same level with AOA-2. The optimization program of AOA-2 has generated two derivatives (RW01 and RW06) with best effect against interaction of GNB with host cells, specifically against <jats:italic>P. aeruginosa<\/jats:italic> and <jats:italic>E. coli<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fmicb.2021.634323","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T19:55:59Z","timestamp":1613246159000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["AOA-2 Derivatives as Outer Membrane Protein A Inhibitors for Treatment of Gram-Negative Bacilli Infections"],"prefix":"10.3389","volume":"12","author":[{"given":"Rafael","family":"Ayerbe-Algaba","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Bay\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ester","family":"Verd\u00fa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Parra-Mill\u00e1n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Seco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meritxell","family":"Teixid\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jer\u00f3nimo","family":"Pach\u00f3n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernest","family":"Giralt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Younes","family":"Smani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1128\/JB.95.5.1520-1541.1968","article-title":"A study of the Moraxella group. 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