{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:49:17Z","timestamp":1788058157911,"version":"build-2784847793"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFD1800100"],"award-info":[{"award-number":["2023YFD1800100"]}]},{"name":"Natural Science Foundation for the Excellent Youth Scholars of Heilongjiang Province of China","award":["YQ2024C017"],"award-info":[{"award-number":["YQ2024C017"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32102726"],"award-info":[{"award-number":["32102726"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>S. suis is a prominent zoonotic pathogen responsible for diseases such as arthritis in piglets, swine septicemia, and meningitis. The emergence of multi-drug resistance (MDR) underscores the urgent need for the development of novel antibacterial strategies. In this context, a systematic evaluation of the antibacterial potential of the bacteriophage lytic enzyme Ply900 was conducted in this study, along with an analysis of its domain functions and an in vivo study of its therapeutic dynamics. Ply900 exhibits potent in vitro lytic activity against multiple bacteria, including Streptococcus suis, Streptococcus agalactiae, and Staphylococcus aureus. Notably, it possesses broad biochemical stability, with tolerance to diverse environmental conditions. In a mouse model of S. suis serotype 2 SC19 infection, both the direct Ply900 treatment group and the triple therapy group achieved effective eradication of S. suis, with markedly improved survival rates. The remaining bacteria remained susceptible to Ply900, with no evidence of induced resistance development. Mechanistic analysis revealed that the SH3B domain of Ply900 enhances targeted cleavage efficiency by binding synergistically to peptidoglycan with the CHAP domain, with CYS-34, HIS-59, and ASP-28 serving as key amino acid sites for Ply900\u2019s cleavage activity. Collectively, these findings lay the foundation for the potential dual applications of the lysin Ply900, both in the clinical treatment of S. suis infections and in the prevention and control of these pathogenic bacteria in livestock farming.<\/jats:p>","DOI":"10.3390\/vetsci13010065","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T09:25:02Z","timestamp":1767950702000},"page":"65","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antibacterial Activity of Bacteriophage Lytic Enzyme Ply900"],"prefix":"10.3390","volume":"13","author":[{"given":"Yuan","family":"Li","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine (Preventive Veterinary Medicine), Northeast Agricultural University, No. 600, Changjiang Road, Xiangfang District, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luxiang","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine (Preventive Veterinary Medicine), Northeast Agricultural University, No. 600, Changjiang Road, Xiangfang District, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine (Preventive Veterinary Medicine), Northeast Agricultural University, No. 600, Changjiang Road, Xiangfang District, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunliu","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine (Preventive Veterinary Medicine), Northeast Agricultural University, No. 600, Changjiang Road, Xiangfang District, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine (Preventive Veterinary Medicine), Northeast Agricultural University, No. 600, Changjiang Road, Xiangfang District, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.medmal.2017.10.001","article-title":"Understanding the virulence of Streptococcus suis: A veterinary, medical, and economic challenge","volume":"48","author":"Haas","year":"2018","journal-title":"Med. Mal. Infect."},{"key":"ref_2","first-page":"mgen000952","article-title":"Streptococcus suis outbreak caused by an emerging zoonotic strain with acquired multi-drug resistance in Thailand","volume":"9","author":"Brizuela","year":"2023","journal-title":"Microb. Genom."},{"key":"ref_3","first-page":"e01367-19","article-title":"Five complete genome sequences spanning the dutch Streptococcus suis serotype 2 and serotype 9 populations","volume":"9","author":"Roodsant","year":"2020","journal-title":"Microbiol. Resour. Announc."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Guo, G., Wang, Z., Li, Q., Yu, Y., Li, Y., Tan, Z., and Zhang, W. (2022). Genomic characterization of Streptococcus parasuis, a close relative of Streptococcus suis and also a potential opportunistic zoonotic pathogen. BMC Genom., 23.","DOI":"10.1186\/s12864-022-08710-6"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.vetmic.2018.07.008","article-title":"Emergence of a vanG-carrying and multidrug resistant ICE in zoonotic pathogen Streptococcus suis","volume":"222","author":"Huang","year":"2018","journal-title":"Vet. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13567-022-01111-3","article-title":"How Streptococcus suis escapes antibiotic treatments","volume":"53","author":"Fraile","year":"2022","journal-title":"Vet. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Huang, J., Ma, J., Shang, K., Hu, X., Liang, Y., Li, D., Wu, Z., Dai, L., Chen, L., and Wang, L. (2016). Evolution and diversity of the antimicrobial resistance associated mobilome in Streptococcus suis: A probable mobile genetic elements reservoir for other streptococci. Front. Cell. Infect. Microbiol., 6.","DOI":"10.3389\/fcimb.2016.00118"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.vetmic.2008.05.013","article-title":"Isolation and identification of a bacteriophage capable of infecting Streptococcus suis type 2 strains","volume":"132","author":"Ma","year":"2008","journal-title":"Vet. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.ygeno.2013.04.005","article-title":"Comparative genomic analysis of twelve Streptococcus suis (pro) phages","volume":"101","author":"Tang","year":"2013","journal-title":"Genomics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23919","DOI":"10.1038\/s41598-021-03370-0","article-title":"Genome analysis provides insight into hyper-virulence of Streptococcus suis LSM178, a human strain with a novel sequence type 1005","volume":"11","author":"Hu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Osei, E.K., Mahony, J., and Kenny, J.G. (2022). From Farm to Fork: Streptococcus suis as a model for the development of novel phage-based biocontrol agents. Viruses, 14.","DOI":"10.3390\/v14091996"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8272","DOI":"10.1128\/AEM.05151-11","article-title":"Application of a bacteriophage lysin to disrupt biofilms formed by the animal pathogen Streptococcus suis","volume":"77","author":"Meng","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, Z., Ma, J., Wang, J., Yang, D., Kong, L., Fu, Q., Cheng, Y., Wang, H., Yan, Y., and Sun, J. (2019). Application of the phage lysin Ply5218 in the treatment of Streptococcus suis infection in piglets. Viruses, 11.","DOI":"10.3390\/v11080715"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1128\/AAC.02526-12","article-title":"Novel bacteriophage lysin with broad lytic activity protects against mixed infection by Streptococcus pyogenes and methicillin-resistant Staphylococcus aureus","volume":"57","author":"Gilmer","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Binte Muhammad Jai, H.S., Dam, L.C., Tay, L.S., Koh, J.J.W., Loo, H.L., Kline, K.A., and Goh, B.C. (2020). Engineered lysins with customized lytic activities against enterococci and staphylococci. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.574739"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1038\/s41396-023-01463-4","article-title":"Conjugative transfer of streptococcal prophages harboring antibiotic resistance and virulence genes","volume":"17","author":"Huang","year":"2023","journal-title":"ISME J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Uru\u00e9n, C., Gimeno, J., Sanz, M., Fraile, L., Mar\u00edn, C.M., and Arenas, J. (2024). Invasive Streptococcus suis isolated in Spain contain a highly promiscuous and dynamic resistome. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1329632"},{"key":"ref_18","first-page":"001224","article-title":"Virulence genes, resistome and mobilome of Streptococcus suis strains isolated in France","volume":"10","author":"Lucas","year":"2024","journal-title":"Microb. Genom."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16506","DOI":"10.1038\/s41598-017-16736-0","article-title":"Csl2, a novel chimeric bacteriophage lysin to fight infections caused by Streptococcus suis, an emerging zoonotic pathogen","volume":"7","author":"Domenech","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.copbio.2021.01.012","article-title":"Application of bacteriophage-derived endolysins to combat streptococcal disease: Current state and perspectives","volume":"68","author":"Linden","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11018","DOI":"10.1074\/jbc.M111.318584","article-title":"LytA, major autolysin of Streptococcus pneumoniae, requires access to nascent peptidoglycan","volume":"287","author":"Mellroth","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1042\/BCJ20210701","article-title":"The structure and function of modular Escherichia coli O157: H7 bacteriophage FTBEc1 endolysin, LysT84: Defining a new endolysin catalytic subfamily","volume":"479","author":"Love","year":"2022","journal-title":"Biochem. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1007\/s00284-011-0018-y","article-title":"LysGH15B, the SH3b domain of staphylococcal phage endolysin LysGH15, retains high affinity to staphylococci","volume":"63","author":"Gu","year":"2011","journal-title":"Curr. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5965","DOI":"10.1038\/s41598-019-42435-z","article-title":"Structural bases of peptidoglycan recognition by lysostaphin SH3b domain","volume":"9","author":"Mitkowski","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.gene.2009.04.023","article-title":"Differentially conserved staphylococcal SH3b_5 cell wall binding domains confer increased staphylolytic and streptolytic activity to a streptococcal prophage endolysin domain","volume":"443","author":"Becker","year":"2009","journal-title":"Gene"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/1743-422X-11-133","article-title":"Crystal structure of the lytic CHAPK domain of the endolysin LysK from Staphylococcus aureus bacteriophage K","volume":"11","author":"Keary","year":"2014","journal-title":"Virol. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134634","DOI":"10.1016\/j.ijbiomac.2024.134634","article-title":"Endolysin CHAP domain-carbosilane metallodendrimer complexes with triple action on Gram-negative bacteria: Membrane destabilization, reactive oxygen species production and peptidoglycan degradation","volume":"278","author":"Lach","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7377","DOI":"10.1128\/AEM.02300-15","article-title":"Prophage lysin Ply30 protects mice from Streptococcus suis and Streptococcus equi subsp. zooepidemicus infections","volume":"81","author":"Tang","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"fnw186","DOI":"10.1093\/femsle\/fnw186","article-title":"A novel prophage lysin Ply5218 with extended lytic activity and stability against Streptococcus suis infection","volume":"363","author":"Zhang","year":"2016","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_30","first-page":"mgen000992","article-title":"Transcriptomics in serum and culture medium reveal shared and differential gene regulation in pathogenic and commensal Streptococcus suis","volume":"9","author":"Fredriksen","year":"2023","journal-title":"Microb. Genom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"918","DOI":"10.3390\/biology2030918","article-title":"Bacterial adhesion of Streptococcus suis to host cells and its inhibition by carbohydrate ligands","volume":"2","author":"Kouki","year":"2013","journal-title":"Biology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.micpath.2018.03.061","article-title":"Identification of oligopeptide-binding protein (OppA) and its role in the virulence of Streptococcus suis serotype 2","volume":"118","author":"Zheng","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_33","first-page":"6513","article-title":"Capsular polysaccharide switching in Streptococcus suis modulates host cell interactions and virulence","volume":"11","author":"Maruyama","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/jam.14149","article-title":"Silibinin attenuates Streptococcus suis serotype 2 virulence by targeting suilysin","volume":"126","author":"Shen","year":"2019","journal-title":"J. Appl. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Song, L., Li, X., Xiao, Y., Huang, Y., Jiang, Y., Meng, G., and Ren, Z. (2020). Contribution of Nlrp3 inflammasome activation mediated by suilysin to streptococcal toxic shock-like syndrome. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01788"}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/1\/65\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T05:16:21Z","timestamp":1768108581000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/13\/1\/65"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["vetsci13010065"],"URL":"https:\/\/doi.org\/10.3390\/vetsci13010065","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]}}}