{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T23:56:11Z","timestamp":1769039771352,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2025YFC3408500"],"award-info":[{"award-number":["2025YFC3408500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270151"],"award-info":[{"award-number":["32270151"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A novel lytic bacteriophage, XAN_XB1, was isolated from hospital wastewater through host bacterial enrichment and evaluated for its potential in controlling multidrug-resistant Stenotrophomonas maltophilia infections. Transmission electron microscopy revealed that XAN_XB1 has a long tail, possessing an icosahedral head of ~80 nm in diameter and a tail measuring ~150 nm in length. It produced clear plaques of 0.5\u20131 mm on host bacterial lawns. Host range analysis demonstrated its ability to infect multiple multidrug-resistant S. maltophilia isolates. Biological characterization showed that the phage is chloroform-insensitive, retains strong lytic activity across a wide temperature (4\u201360 \u00b0C) and pH (3.0\u201310.0) range, and achieves more rapid host suppression under higher multiplicity of infection (MOI). Whole-genome sequencing determined a ~47 kb double-stranded DNA genome encoding 71 predicted open reading frames, with no known virulence or antibiotic resistance genes. Phylogenetic analysis of MCP and terminase large subunit sequences placed XAN_XB1 in a unique Caudoviricetes, with ANI values below the 95% ICTV threshold verifying its status as a novel phage species. The XAN_XB1 therapy significantly alleviates S. maltophilia infection-induced severe pulmonary inflammatory lesions, high mortality, elevated serum inflammatory factors and massive pulmonary bacterial colonization in male BALB\/c mice, confirming its favorable therapeutic effect on such infections. Collectively, these results reveal that is an efficacious candidate for therapeutic development against S. maltophilia infections.<\/jats:p>","DOI":"10.3390\/ijms27020944","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:24:34Z","timestamp":1768901074000},"page":"944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Potential of a Novel Stenotrophomonas maltophilia Phage XAN_XB1: Isolation, Characterization, Genome Analysis and Evaluation in Mice Model"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6046-5465","authenticated-orcid":false,"given":"Qingqing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoyu","family":"Gan","sequence":"additional","affiliation":[{"name":"BioBank, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhonglin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cao","family":"Qiu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yawen","family":"Wang","sequence":"additional","affiliation":[{"name":"BioBank, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-6115","authenticated-orcid":false,"given":"Bing","family":"Liu","sequence":"additional","affiliation":[{"name":"BioBank, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1107-7965","authenticated-orcid":false,"given":"Xiaoyan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis","volume":"399","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nrmicro1325","article-title":"Antimicrobial-resistant bacteria in the community setting","volume":"4","author":"Furuya","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3934\/microbiol.2018.3.482","article-title":"An overview of the antimicrobial resistance mechanisms of bacteria","volume":"4","author":"Reygaert","year":"2018","journal-title":"AIMS Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.ajic.2006.05.219","article-title":"Mechanisms of antimicrobial resistance in bacteria","volume":"34","author":"Tenover","year":"2006","journal-title":"Am. J. Infect. Control"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.tim.2018.04.006","article-title":"Stenotrophomonas\u00a0maltophilia","volume":"26","author":"An","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e4375","DOI":"10.1097\/MD.0000000000004375","article-title":"Risk factors for mortality in patients with Stenotrophomonas maltophilia bacteremia","volume":"95","author":"Jeon","year":"2016","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"dlac040","DOI":"10.1093\/jacamr\/dlac040","article-title":"Clinical challenges treating Stenotrophomonas maltophilia infections: An update","volume":"4","author":"Mojica","year":"2022","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"arba-0005\u20132017","DOI":"10.1128\/microbiolspec.ARBA-0005-2017","article-title":"Antimicrobial Resistance in Stenotrophomonas spp.","volume":"6","author":"Wang","year":"2018","journal-title":"Microbiol. Spectr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e0003019","DOI":"10.1128\/CMR.00030-19","article-title":"Advances in the Microbiology of Stenotrophomonas maltophilia","volume":"34","author":"Brooke","year":"2021","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Duan, Z., Qin, J., Liu, Y., Li, C., and Ying, C. (2020). Molecular epidemiology and risk factors of Stenotrophomonas maltophilia infections in a Chinese teaching hospital. BMC Microbiol., 20.","DOI":"10.1186\/s12866-020-01985-3"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e0403022","DOI":"10.1128\/spectrum.04030-22","article-title":"Efficacy in Galleria mellonella Larvae and Application Potential. Assessment of a New Bacteriophage BUCT700 Extensively Lyse Stenotrophomonas maltophilia","volume":"11","author":"Li","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s00284-022-02869-7","article-title":"Stenotrophomonas maltophilia: Genotypic Characterization of Virulence Genes and the Effect of Ascorbic Acid on Biofilm Formation","volume":"79","author":"ElBaradei","year":"2022","journal-title":"Curr. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15401","DOI":"10.1021\/acs.jafc.4c00454","article-title":"Recent Advances in Microfluidics for the Early Detection of Plant Diseases in Vegetables, Fruits, and Grains Caused by Bacteria, Fungi, and Viruses","volume":"72","author":"Zhao","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Niazi, S.K. (2025). Bacteriophage Therapy: Discovery, Development, and FDA Approval Pathways. Pharmaceuticals, 18.","DOI":"10.3390\/ph18081115"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e208","DOI":"10.1016\/S1473-3099(21)00612-5","article-title":"Safety and efficacy of phage therapy in difficult-to-treat infections: A systematic review","volume":"22","author":"Uyttebroek","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_16","first-page":"424","article-title":"Expert consensus on management of clinical application of phage therapy (2024 version)","volume":"17","author":"Alliance","year":"2024","journal-title":"Chin. J. Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/CMR.00019-11","article-title":"Stenotrophomonas maltophilia: An emerging global opportunistic pathogen","volume":"25","author":"Brooke","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Costa, S.P., Cunha, A.P., Freitas, P.P., and Carvalho, C.M. (2022). A Phage Receptor-Binding Protein as a Promising Tool for the Detection of Escherichia coli in Human Specimens. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.871855"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"McCutcheon, J.G., Peters, D.L., and Dennis, J.J. (2018). Identification and Characterization of Type IV Pili as the Cellular Receptor of Broad Host Range Stenotrophomonas maltophilia Bacteriophages DLP1 and DLP2. Viruses, 10.","DOI":"10.3390\/v10060338"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Han, P., Zhang, W., Pu, M., Li, Y., Song, L., An, X., Li, M., Li, F., Zhang, S., and Fan, H. (2022). Characterization of the Bacteriophage BUCT603 and Therapeutic Potential Evaluation Against Drug-Resistant Stenotrophomonas maltophilia in a Mouse Model. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.906961"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Peters, D.L., McCutcheon, J.G., and Dennis, J.J. (2020). Characterization of Novel Broad-Host-Range Bacteriophage DLP3 Specific to Stenotrophomonas maltophilia as a Potential Therapeutic Agent. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01358"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"McCutcheon, J.G., Lin, A., and Dennis, J.J. (2020). Isolation and Characterization of the Novel Bacteriophage AXL3 against Stenotrophomonas maltophilia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176338"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fanaei Pirlar, R., Wagemans, J., Kunisch, F., Lavigne, R., Trampuz, A., and Gonzalez Moreno, M. (2022). Novel Stenotrophomonas maltophilia Bacteriophage as Potential Therapeutic Agent. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14102216"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Turner, D., Kropinski, A.M., and Adriaenssens, E.M. (2021). A Roadmap for Genome-Based Phage Taxonomy. Viruses, 13.","DOI":"10.3390\/v13030506"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pompilio, A., Pomponio, S., Crocetta, V., Gherardi, G., Verginelli, F., Fiscarelli, E., Dicuonzo, G., Savini, V., D\u2019Antonio, D., and Di Bonaventura, G. (2011). Phenotypic and genotypic characterization of Stenotrophomonas maltophilia isolates from patients with cystic fibrosis: Genome diversity, biofilm formation, and virulence. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-159"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1574-6968.2011.02452.x","article-title":"Stenotrophomonas interspecies differentiation and identification by gyrB sequence analysis","volume":"327","author":"Mihaylova","year":"2012","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pompilio, A., Crocetta, V., Ghosh, D., Chakrabarti, M., Gherardi, G., Vitali, L.A., Fiscarelli, E., and Di Bonaventura, G. (2016). Stenotrophomonas maltophilia Phenotypic and Genotypic Diversity during a 10-year Colonization in the Lungs of a Cystic Fibrosis Patient. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01551"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1128\/JCM.42.2.693-699.2003","article-title":"High genetic diversity among Stenotrophomonas maltophilia strains despite their originating at a single hospital","volume":"42","author":"Valdezate","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s00705-024-06148-7","article-title":"Characterization and genomic analysis of phage vB_SmaP_c9-N, a novel Stenotrophomonas maltophilia podophage with antibiofilm activity","volume":"169","author":"Xi","year":"2024","journal-title":"Arch. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ijantimicag.2010.10.025","article-title":"Stenotrophomonas maltophilia resistance to trimethoprim\/sulfamethoxazole mediated by acquisition of sul and dfrA genes in a plasmid-mediated class 1 integron","volume":"37","author":"Hu","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Peters, D.L., Davis, C.M., Harris, G., Zhou, H., Rather, P.N., Hrapovic, S., Lam, E., Dennis, J.J., and Chen, W. (2023). Characterization of Virulent T4-like Acinetobacter baumannii Bacteriophages DLP1 and DLP2. Viruses, 15.","DOI":"10.3390\/v15030739"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cheng, P., Li, Z., Liu, L., Li, R., Zhou, J., Luo, X., Mu, X., Sun, J., Ma, J., and A, X. (2025). Characterization and antimicrobial activity of a novel lytic phage vB_SmaS_QH16 against Stenotrophomonas maltophilia: In vitro, in vivo, and biofilm studies. Front. Cell Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1610857"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10299","DOI":"10.1038\/s41598-022-14025-z","article-title":"Characterization of Stenotrophomonas maltophilia phage AXL1 as a member of the genus Pamexvirus encoding resistance to trimethoprim-sulfamethoxazole","volume":"12","author":"McCutcheon","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"fnae076","DOI":"10.1093\/femsle\/fnae076","article-title":"Isolation, characterization, and genomic analysis of BUCT627: A lytic bacteriophage targeting Stenotrophomonas maltophilia","volume":"371","author":"Hou","year":"2024","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"btac776","DOI":"10.1093\/bioinformatics\/btac776","article-title":"Pharokka: A fast scalable bacteriophage annotation tool","volume":"39","author":"Bouras","year":"2023","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"W244","DOI":"10.1093\/nar\/gki408","article-title":"The HHpred interactive server for protein homology detection and structure prediction","volume":"33","author":"Soding","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"D912","DOI":"10.1093\/nar\/gkab1107","article-title":"VFDB 2022: A general classification scheme for bacterial virulence factors","volume":"50","author":"Liu","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_39","first-page":"000748","article-title":"ResFinder\u2014An open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes","volume":"8","author":"Florensa","year":"2022","journal-title":"Microb. Genom."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"W484","DOI":"10.1093\/nar\/gkad326","article-title":"Proksee: In-depth characterization and visualization of bacterial genomes","volume":"51","author":"Grant","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: Improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1093\/bioinformatics\/btp348","article-title":"trimAl: A tool for automated alignment trimming in large-scale phylogenetic analyses","volume":"25","author":"Gabaldon","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1093\/molbev\/msaa015","article-title":"IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era","volume":"37","author":"Minh","year":"2020","journal-title":"Mol. Biol. Evol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"W587","DOI":"10.1093\/nar\/gkad359","article-title":"Tree Visualization By One Table (tvBOT): A web application for visualizing, modifying and annotating phylogenetic trees","volume":"51","author":"Xie","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Moraru, C., Varsani, A., and Kropinski, A.M. (2020). VIRIDIC-A Novel Tool to Calculate the Intergenomic Similarities of Prokaryote-Infecting Viruses. Viruses, 12.","DOI":"10.1101\/2020.07.05.188268"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Pu, M., Li, Y., Han, P., Lin, W., Geng, R., Qu, F., An, X., Song, L., Tong, Y., and Zhang, S. (2022). Genomic characterization of a new phage BUCT541 against Klebsiella pneumoniae K1-ST23 and efficacy assessment in mouse and Galleria mellonella larvae. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.950737"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T08:50:10Z","timestamp":1768985410000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,18]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020944"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020944","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,18]]}}}