{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:14:59Z","timestamp":1790007299660,"version":"4.0.1"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["161B0769C"],"award-info":[{"award-number":["161B0769C"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Infections with antibiotic-resistant Gram-negative pathogens represent a major global threat to public health. Acinetobacter baumannii is a highly important nosocomial pathogen causing severe and life-threatening infections, like pneumonia, wound infections, or sepsis. It is often resistant even against last-resort antibiotics, such as carbapenems, and can persist in healthcare settings. Artilysin\u00aes are a novel class of endolysins targeted against multidrug-resistant bacteria. Methods: Antibacterial activity of Art-Top3 was determined by broth microdilution, in vitro assays and in the Galleria mellonella infection model. The toxicity of Art-Top3 on red blood cells, endothelial and epithelial cells was analyzed using the MTT assay. Results: Here, we report on a new Artilysin\u00ae Art-Top3 that is active against A. baumannii and led to a 105-fold reduction in viable A. baumannii after five minutes of exposure. Art-Top3 showed activity against A. baumannii biofilms in static and dynamic experimental infection models. Furthermore, upon infection with carbapenem-resistant A. baumannii patient isolates, Art-Top3 was able to rescue human primary cells in vitro and larvae of Galleria mellonella in an in vivo infection model. Art-Top3 did not lyse human red blood cells and showed activity in human serum, indicating a low toxicity and high stability of Art-Top3 in vitro. Conclusion: Our findings collectively establish that Art-Top3 might be a candidate for novel therapeutic strategies of infections caused by multidrug-resistant A. baumannii pathogens.<\/jats:p>","DOI":"10.3390\/antibiotics14020162","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T06:30:29Z","timestamp":1738823429000},"page":"162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bactericidal Effect of a Novel Phage Endolysin Targeting Multi-Drug-Resistant Acinetobacter baumannii"],"prefix":"10.3390","volume":"14","author":[{"given":"Sara","family":"Garcia Torres","sequence":"first","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Institute of Medical Microbiology and Infection Control, 60596 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9728-4032","authenticated-orcid":false,"given":"Dirk","family":"Henrich","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Department of Trauma Surgery and Orthopedics, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene D.","family":"Verboket","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Department of Trauma Surgery and Orthopedics, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-2910","authenticated-orcid":false,"given":"Ingo","family":"Marzi","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Department of Trauma Surgery and Orthopedics, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Hahne","sequence":"additional","affiliation":[{"name":"Lysando Innovations Lab GmbH, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3321-7551","authenticated-orcid":false,"given":"Volkhard A. J.","family":"Kempf","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Institute of Medical Microbiology and Infection Control, 60596 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-5309","authenticated-orcid":false,"given":"Stephan","family":"G\u00f6ttig","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt, University Hospital, Institute of Medical Microbiology and Infection Control, 60596 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1128\/CMR.00058-07","article-title":"Acinetobacter baumannii: Emergence of a Successful Pathogen","volume":"21","author":"Peleg","year":"2008","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ayoub Moubareck, C., and Hammoudi Halat, D. (2020). Insights into Acinetobacter Baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen. Antibiotics, 9.","DOI":"10.3390\/antibiotics9030119"},{"key":"ref_3","first-page":"363","article-title":"Acinetobacter baumannii: An Emerging and Important Pathogen","volume":"17","author":"Alsan","year":"2010","journal-title":"J. Clin. Outcomes Manag."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wong, D., Nielsen, T.B., Bonomo, R.A., Pantapalangkoor, P., Luna, B., and Spellberg, B. (2016). Clinical and Pathophysiological Overview of Acinetobacter Infections: A Century of Challenges. Clin. Microbiol. Rev., 30.","DOI":"10.1128\/CMR.00058-16"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Morris, F.C., Dexter, C., Kostoulias, X., Uddin, M.I., and Peleg, A.Y. (2019). The Mechanisms of Disease Caused by Acinetobacter baumannii. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01601"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1093\/jac\/dkz080","article-title":"Identification of the Novel Class D \u03b2-Lactamase OXA-679 Involved in Carbapenem Resistance in Acinetobacter calcoaceticus","volume":"74","author":"Tietgen","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1586\/eri.13.38","article-title":"Screening and Deciphering Antibiotic Resistance in Acinetobacter baumannii: A State of the Art","volume":"11","author":"Bonnin","year":"2013","journal-title":"Expert. Rev. Anti-Infect. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1002\/iub.532","article-title":"Genetic Basis of Antibiotic Resistance in Pathogenic Acinetobacter Species","volume":"63","author":"Poirel","year":"2011","journal-title":"IUBMB Life"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"787","DOI":"10.12998\/wjcc.v2.i12.787","article-title":"Antimicrobial Resistance in Acinetobacter baumannii: From Bench to Bedside","volume":"2","author":"Lin","year":"2014","journal-title":"World J. Clin. Cases"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1093\/jac\/dku170","article-title":"Detection of Pan Drug-Resistant Acinetobacter baumannii in Germany","volume":"69","author":"Gruber","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105844","DOI":"10.1016\/j.ijantimicag.2019.11.001","article-title":"Endolysins as Emerging Alternative Therapeutic Agents to Counter Drug-Resistant Infections","volume":"55","author":"Gondil","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Murray, E., Draper, L.A., Ross, R.P., and Hill, C. (2021). The Advantages and Challenges of Using Endolysins in a Clinical Setting. Viruses, 13.","DOI":"10.3390\/v13040680"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1574-6968.2012.02573.x","article-title":"Isolation and Characterization of Wide Host Range Lytic Bacteriophage AP22 Infecting Acinetobacter baumannii","volume":"332","author":"Popova","year":"2012","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1007\/s00705-012-1320-0","article-title":"Novel Lytic Bacteriophage AB7-IBB1 of Acinetobacter baumannii: Isolation, Characterization and Its Effect on Biofilm","volume":"157","author":"Yele","year":"2012","journal-title":"Arch. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3774","DOI":"10.1128\/AAC.02668-14","article-title":"Art-175 Is a Highly Efficient Antibacterial Against Multidrug-Resistant Strains and Persisters of Pseudomonas aeruginosa","volume":"58","author":"Briers","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1111\/j.1365-2672.2010.04931.x","article-title":"Use of Bacteriophage Endolysin EL188 and Outer Membrane Permeabilizers Against Pseudomonas aeruginosa","volume":"110","author":"Briers","year":"2011","journal-title":"J. Appl. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1021\/acsinfecdis.1c00222","article-title":"Membrane-Permeable Antibacterial Enzyme Against Multidrug-Resistant Acinetobacter baumannii","volume":"7","author":"Chen","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s40121-017-0153-2","article-title":"Minocycline for the Treatment of Multidrug and Extensively Drug-Resistant A. baumannii: A Review","volume":"6","author":"Lashinsky","year":"2017","journal-title":"Infect. Dis. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/21505594.2018.1558693","article-title":"The Acinetobacter Trimeric Autotransporter Adhesin Ata Controls Key Virulence Traits of Acinetobacter baumannii","volume":"10","author":"Weidensdorfer","year":"2019","journal-title":"Virulence"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tomaschek, F., Higgins, P.G., Stefanik, D., Wisplinghoff, H., and Seifert, H. (2016). Head-to-Head Comparison of Two Multi-Locus Sequence Typing (MLST) Schemes for Characterization of Acinetobacter baumannii Outbreak and Sporadic Isolates. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153014"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Blasco, L., Ambroa, A., Trastoy, R., Bleriot, I., Moscoso, M., Fern\u00e1ndez-Garcia, L., Perez-Nadales, E., Fern\u00e1ndez-Cuenca, F., Torre-Cisneros, J., and Oteo-Iglesias, J. (2020). In Vitro and In Bivo Efficacy of Combinations of Colistin and Different Endolysins Against Clinical Strains of Multi-Drug Resistant Pathogens. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-64145-7"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s12275-022-2107-y","article-title":"Eradication of Drug-Resistant Acinetobacter baumannii by Cell-Penetrating Peptide Fused Endolysin","volume":"60","author":"Lim","year":"2022","journal-title":"J. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liu, W., Wu, Z., Mao, C., Guo, G., Zeng, Z., Fei, Y., Wan, S., Peng, J., and Wu, J. (2020). Antimicrobial Peptide Cec4 Eradicates the Bacteria of Clinical Carbapenem-Resistant Acinetobacter baumannii Biofilm. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01532"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Roca, I., Espinal, P., Vila-Farr\u00e9s, X., and Vila, J. (2012). The Acinetobacter baumannii Oxymoron: Commensal Hospital Dweller Turned Pan-Drug-Resistant Menace. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2012.00148"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Choi, Y.-J., Kim, S., Bae, S., Kim, Y., Chang, H.-H., and Kim, J. (2022). Antibacterial Effects of Recombinant Endolysins in Disinfecting Medical Equipment: A Pilot Study. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.773640"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"eaaz1136","DOI":"10.1126\/sciadv.aaz1136","article-title":"A VersaTile-Driven Platform for Rapid Hit-to-Lead Development of Engineered Lysins","volume":"6","author":"Gerstmans","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chu, J.J.K., Poh, W.H., Hasnuddin, N.T.B., Hew, E.Y., Dam, L.C., Sahili, A.E., Rice, S.A., and Goh, B.C. (2022). Novel Phage Lysin Abp013 Against Acinetobacter baumannii. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020169"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Khan, F.M., Rasheed, F., Yang, Y., Liu, B., and Zhang, R. (2024). Endolysins: A New Antimicrobial Agent Against Antimicrobial Resistance. Strategies and Opportunities in Overcoming the Challenges of Endolysins Against Gram-Negative Bacteria. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1385261"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rahman, M.u., Wang, W., Sun, Q., Shah, J.A., Li, C., Sun, Y., Li, Y., Zhang, B., Chen, W., and Wang, S. (2021). Endolysin, a Promising Solution Against Antimicrobial Resistance. Antibiotics, 10.","DOI":"10.3390\/antibiotics10111277"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Antonova, N.P., Vasina, D.V., Rubalsky, E.O., Fursov, M.V., Savinova, A.S., Grigoriev, I.V., Usachev, E.V., Shevlyagina, N.V., Zhukhovitsky, V.G., and Balabanyan, V.U. (2020). Modulation of Endolysin LysECD7 Bactericidal Activity by Different Peptide Tag Fusion. Biomolecules, 10.","DOI":"10.3390\/biom10030440"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Peng, S.-Y., You, R.-I., Lai, M.-J., Lin, N.-T., Chen, L.-K., and Chang, K.-C. (2017). Highly Potent Antimicrobial Modified Peptides Derived from the Acinetobacter baumannii Phage Endolysin LysAB2. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-11832-7"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhang, H., Zhang, X., Liang, S., Wang, J., Zhu, Y., Zhang, W., Liu, S., Schwarz, S., and Xie, F. (2023). Bactericidal Synergism between Phage Endolysin Ply2660 and Cathelicidin LL-37 Against Vancomycin-Resistant Enterococcus faecalis Biofilms. NPJ Biofilms Microbiomes, 9.","DOI":"10.1038\/s41522-023-00385-5"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Son, S.M., Kim, J., and Ryu, S. (2023). Development of Sensitizer Peptide-Fused Endolysin Lys1S-L9P Acting Against Multidrug-Resistant Gram-Negative Bacteria. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1296796"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Islam, M.M., Kim, D., Kim, K., Park, S.-J., Akter, S., Kim, J., Bang, S., Kim, S., Kim, J., and Lee, J.C. (2022). Engineering of Lysin by Fusion of Antimicrobial Peptide (Cecropin A) Enhances Its Antibacterial Properties Against Multidrug-Resistant Acinetobacter baumannii. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.988522"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1128\/AAC.01533-08","article-title":"Galleria Mellonella as a Model System to Study Acinetobacter baumannii Pathogenesis and Therapeutics","volume":"53","author":"Peleg","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Leukert, L., Tietgen, M., Krause, F.F., Schultze, T.G., Fuhrmann, D.C., Debruyne, C., Salcedo, S.P., Visekruna, A., Wittig, L., and G\u00f6ttig, S. (2023). Infection of Endothelial Cells with Acinetobacter baumannii Reveals Remodelling of Mitochondrial Protein Complexes. Microbiol. Spectr., 11.","DOI":"10.1128\/spectrum.05174-22"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Jeong, T.-H., Hong, H.-W., Kim, M.S., Song, M., and Myung, H. (2023). Characterization of Three Different Endolysins Effective Against Gram-Negative Bacteria. Viruses, 15.","DOI":"10.3390\/v15030679"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sykilinda, N.N., Nikolaeva, A.Y., Shneider, M.M., Mishkin, D.V., Patutin, A.A., Popov, V.O., Boyko, K.M., Klyachko, N.L., and Miroshnikov, K.A. (2018). Structure of an Acinetobacter Broad-Range Prophage Endolysin Reveals a C-Terminal \u03b1-Helix with the Proposed Role in Activity Against Live Bacterial Cells. Viruses, 10.","DOI":"10.3390\/v10060309"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1099\/00207713-18-3-207","article-title":"A Comparison of 120 Strains of Bacterium Anitratum Schaub and Hauber with the Type Strain of This Species","volume":"18","author":"Hugh","year":"1968","journal-title":"Int. J. Bacteriol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105172","DOI":"10.1016\/j.micinf.2023.105172","article-title":"Adhesion of Human Pathogenic Bacteria to Endothelial Cells Is Facilitated by Fibronectin Interaction","volume":"25","author":"Vaca","year":"2023","journal-title":"Microbes Infect."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hong, M.J., Kim, M.K., and Park, Y. (2021). Comparative Antimicrobial Activity of Hp404 Peptide and Its Analogs Against Acinetobacter baumannii. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115540"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/2\/162\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:27:55Z","timestamp":1760027275000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/2\/162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["antibiotics14020162"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14020162","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,6]]}}}