{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:04:02Z","timestamp":1789416242589,"version":"build-2803163510"},"reference-count":176,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"abstract":"<jats:p>\n                    The global rise of multidrug\u2010resistant (MDR) bacteria has renewed interest in bacteriophage-derived enzymes as alternative antibacterials. Phage\u2010encoded lytic proteins\u2014including holins, endolysins, polysaccharide depolymerases, and virion\u2010associated lysins (VALs)\u2014act via distinct mechanisms to disrupt bacterial cells or their protective polysaccharide barriers. Holins accumulate in the bacterial membrane and suddenly form pores, enabling endolysins to access and cleave peptidoglycan bonds. Endolysins are peptidoglycan hydrolases (glycosidases, amidases, endopeptidases, etc.) that cause rapid osmotic lysis of Gram\u2010positive pathogens and, if engineered (\n                    <jats:italic toggle=\"yes\">e.g.,<\/jats:italic>\n                    fused to membrane\u2010penetrating peptides), can kill Gram\u2010negative bacteria from without. Polysaccharide depolymerases degrade bacterial capsules, biofilm exopolysaccharides and LPS O\u2010antigens, stripping away virulence factors and exposing underlying cells to phage or host defenses. VALs (or VAPGHs) are phage tail enzymes that locally cleave peptidoglycan at infection onset to permit viral DNA entry. Each class has been studied in natural and engineered forms (\n                    <jats:italic toggle=\"yes\">e.g.,<\/jats:italic>\n                    \u201cartilysins\u201d and \u201cchimeolysins\u201d with optimized activity or spectrum). These proteins exhibit rapid, specific bacteriolysis (often synergistic with antibiotics) and low resistance propensity, but challenges remain in delivery, stability, and immunogenicity. Here, we review the molecular actions, advantages and limitations, and the therapeutic applications of holins, endolysins, depolymerases, and VALs (natural and engineered) against MDR infections.\n                  <\/jats:p>","DOI":"10.1177\/10766294261441705","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T11:48:29Z","timestamp":1779709709000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Endolysins, Depolymerases, Holins, and VALs: Phage-Derived Proteins for Combating Antimicrobial Resistance"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4791-8156","authenticated-orcid":false,"given":"Zahra","family":"Nasiri Shoeibi","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzaneh","family":"Rafiee","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sousan","family":"Akrami","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Ghandehari","sequence":"additional","affiliation":[{"name":"Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Mehdi","family":"Feizabadi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran."},{"name":"Thoracic Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10121497"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/1040841X.2012.723675"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13568-021-01222-8"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2023.08.017"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-023-00919-1"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02629-16"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10020124"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/aem.07050-11"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.enzmictec.2021.109846"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.2205.05009"},{"key":"e_1_3_2_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10111277"},{"key":"e_1_3_2_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05870.x"},{"key":"e_1_3_2_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036991"},{"key":"e_1_3_2_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10040461"},{"key":"e_1_3_2_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/aem.01783-07"},{"key":"e_1_3_2_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.740914"},{"key":"e_1_3_2_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14134"},{"key":"e_1_3_2_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.22.15847"},{"key":"e_1_3_2_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2009.01541.x"},{"key":"e_1_3_2_21_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27063-0"},{"key":"e_1_3_2_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00069-24"},{"key":"e_1_3_2_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.aivir.2018.09.003"},{"key":"e_1_3_2_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44337-025-00424-4"},{"key":"e_1_3_2_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02666-16"},{"key":"e_1_3_2_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-025-01226-1"},{"key":"e_1_3_2_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2024.107222"},{"key":"e_1_3_2_28_1","doi-asserted-by":"publisher","DOI":"10.1159\/000473872"},{"key":"e_1_3_2_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2019.11.001"},{"key":"e_1_3_2_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/aem.00886-18"},{"key":"e_1_3_2_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01625-09"},{"key":"e_1_3_2_32_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.15.8"},{"key":"e_1_3_2_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-12-297"},{"key":"e_1_3_2_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11070966"},{"key":"e_1_3_2_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2020.09.012"},{"key":"e_1_3_2_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.9b00360"},{"key":"e_1_3_2_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40182"},{"key":"e_1_3_2_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-024-02359-4"},{"key":"e_1_3_2_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv038"},{"key":"e_1_3_2_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00311-20"},{"key":"e_1_3_2_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1397830"},{"key":"e_1_3_2_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02009-18"},{"key":"e_1_3_2_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01872-16"},{"key":"e_1_3_2_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/v10070380"},{"key":"e_1_3_2_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/v16050760"},{"key":"e_1_3_2_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/2191-0855-1-29"},{"key":"e_1_3_2_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02927"},{"key":"e_1_3_2_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.854908"},{"key":"e_1_3_2_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2021.01.012"},{"key":"e_1_3_2_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02043-18"},{"key":"e_1_3_2_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119982"},{"key":"e_1_3_2_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt131"},{"key":"e_1_3_2_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2009.04.023"},{"key":"e_1_3_2_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-11-226"},{"key":"e_1_3_2_55_1","doi-asserted-by":"publisher","DOI":"10.4161\/bact.26564"},{"key":"e_1_3_2_56_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01793-13"},{"key":"e_1_3_2_57_1","doi-asserted-by":"publisher","DOI":"10.1080\/08927014.2014.905927"},{"k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