{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:36:59Z","timestamp":1789011419545,"version":"build-2803163510"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32070187"],"award-info":[{"award-number":["32070187"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32161133003"],"award-info":[{"award-number":["32161133003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31770192"],"award-info":[{"award-number":["31770192"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004739","name":"Youth Innovation Promotion Association CAS","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004739","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Calcium-binding motifs are shared by multiple bacteriophage lysins; however, the influence of calcium on the enzymatic activity and host range of these enzymes is still not understood. To address this, ClyF, a chimeric lysin with a putative calcium-binding motif, was used as a model for in vitro and in vivo investigations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The concentration of calcium bound to ClyF was determined by atomic absorption spectrometry. The influence of calcium on the structure, activity and host range of ClyF was assessed by circular dichroism and time\u2013kill assays. The bactericidal activity of ClyF was evaluated in various sera and a mouse model of Streptococcus agalactiae bacteraemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ClyF has a highly negatively charged surface around the calcium-binding motif that can bind extra calcium, thereby increasing the avidity of ClyF for the negatively charged bacterial cell wall. In line with this, ClyF exhibited significantly enhanced staphylolytic and streptolytic activity in various sera containing physiological calcium, including human serum, heat-inactivated human serum, mouse serum and rabbit serum. In a mouse model of S. agalactiae bacteraemia, intraperitoneal administration of a single dose of 25 \u03bcg\/mouse ClyF fully protected the mice from lethal infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The present data collectively showed that physiological calcium improves the bactericidal activity and host range of ClyF, making it a promising candidate for the treatment of infections caused by multiple staphylococci and streptococci.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad059","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T15:55:41Z","timestamp":1678463741000},"page":"1182-1190","source":"Crossref","is-referenced-by-count":6,"title":["Calcium-binding motif-mediated binding of redundant calcium offers a chimeolysin enhanced bactericidal activity and extended host range under physiological conditions"],"prefix":"10.1093","volume":"78","author":[{"given":"Minghui","family":"Jia","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 , China"},{"name":"State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University , Wuhan 430070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanli","family":"Zhou","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dehua","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University , Wuhan 430070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Xue","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Department of Etiology, School of Basic Medical Sciences, Fujian Medical University , Fuzhou 350002 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University , Wuhan 430070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirong","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University , Wuhan 430070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Zhong","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinfeng","family":"Li","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1456-8284","authenticated-orcid":false,"given":"Jin","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University , Wuhan 430070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongping","family":"Wei","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6750-1465","authenticated-orcid":false,"given":"Hang","family":"Yang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences , Wuhan 430071 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"},{"name":"Hubei Jiangxia Laboratory , Wuhan 430000 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"2023050300201654300_dkad059-B1","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1177\/153537020623100402","article-title":"Bacteriophage endolysins as a novel class of antibacterial agents","volume":"231","author":"Borysowski","year":"2006","journal-title":"Exp Biol Med"},{"key":"2023050300201654300_dkad059-B2","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1093\/cid\/ciu543","article-title":"Antimicrobial stewardship: importance for patient and public health","volume":"59","author":"File","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2023050300201654300_dkad059-B3","doi-asserted-by":"crossref","first-page":"604","DOI":"10.3390\/antibiotics9090604","article-title":"Phage therapy, lysin therapy, and antibiotics: a trio due to come","volume":"9","author":"Villa","year":"2020","journal-title":"Antibiotics"},{"key":"2023050300201654300_dkad059-B4","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.biotechadv.2017.12.009","article-title":"Synthetic biology of modular endolysins","volume":"36","author":"Gerstmans","year":"2017","journal-title":"Biotechnol Adv"},{"key":"2023050300201654300_dkad059-B5","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.tim.2005.08.007","article-title":"Bacteriophage lytic enzymes: novel anti-infectives","volume":"13","author":"Fischetti","year":"2005","journal-title":"Trends Microbiol"},{"key":"2023050300201654300_dkad059-B6","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3390\/v10060310","article-title":"Development of phage lysins as novel therapeutics: a historical perspective","volume":"10","author":"Fischetti","year":"2018","journal-title":"Viruses"},{"key":"2023050300201654300_dkad059-B7","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3390\/antibiotics9080466","article-title":"Bacteriophages and lysins as possible alternatives to treat antibiotic-resistant urinary tract infections","volume":"9","author":"Miguel","year":"2020","journal-title":"Antibiotics"},{"key":"2023050300201654300_dkad059-B8","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1046\/j.1365-2958.2002.02889.x","article-title":"C-terminal domains of Listeria monocytogenes bacteriophage murein hydrolases determine specific recognition and high-affinity binding to bacterial cell wall carbohydrates","volume":"44","author":"Loessner","year":"2002","journal-title":"Mol Microbiol"},{"key":"2023050300201654300_dkad059-B9","doi-asserted-by":"crossref","first-page":"5178","DOI":"10.1074\/jbc.M707156200","article-title":"LysM domains from Pteris ryukyuensis chitinase-A: a stability study and characterization of the chitin-binding site","volume":"283","author":"Ohnuma","year":"2008","journal-title":"J Biol Chem"},{"key":"2023050300201654300_dkad059-B10","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":"2023050300201654300_dkad059-B11","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1073\/pnas.061038398","article-title":"Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme","volume":"98","author":"Nelson","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023050300201654300_dkad059-B12","doi-asserted-by":"crossref","first-page":"25063","DOI":"10.1038\/srep25063","article-title":"Triple-acting lytic enzyme treatment of drug-resistant and intracellular Staphylococcus aureus","volume":"6","author":"Becker","year":"2016","journal-title":"Sci Rep"},{"key":"2023050300201654300_dkad059-B13","doi-asserted-by":"crossref","first-page":"7041","DOI":"10.1007\/s00253-019-09955-0","article-title":"Selective antimicrobial activity of cell lytic enzymes in a bacterial consortium","volume":"103","author":"Bhagwat","year":"2019","journal-title":"Appl Microbiol Biotechnol"},{"key":"2023050300201654300_dkad059-B14","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3390\/antibiotics9080447","article-title":"Characterization of clinical MRSA isolates from Northern Spain and assessment of their susceptibility to phage-derived antimicrobials","volume":"9","author":"Salas","year":"2020","journal-title":"Antibiotics"},{"key":"2023050300201654300_dkad059-B15","doi-asserted-by":"crossref","first-page":"e00311-20","DOI":"10.1128\/AAC.00311-20","article-title":"A choline-recognizing monomeric lysin, ClyJ-3m, shows elevated activity against Streptococcus pneumoniae","volume":"64","author":"Luo","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"2023050300201654300_dkad059-B16","doi-asserted-by":"crossref","first-page":"e02291-18","DOI":"10.1128\/AAC.02291-18","article-title":"The antistaphylococcal lysin, CF-301, activates key host factors in human blood to potentiate methicillin-resistant Staphylococcus aureus bacteriolysis","volume":"63","author":"Indiani","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2023050300201654300_dkad059-B17","doi-asserted-by":"crossref","first-page":"40182","DOI":"10.1038\/srep40182","article-title":"A novel chimeric lysin with robust antibacterial activity against planktonic and biofilm methicillin-resistant Staphylococcus aureus","volume":"7","author":"Yang","year":"2017","journal-title":"Sci Rep"},{"key":"2023050300201654300_dkad059-B18","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.3389\/fmicb.2015.01471","article-title":"Antibacterial activity of a novel peptide-modified lysin against Acinetobacter baumannii and Pseudomonas aeruginosa","volume":"6","author":"Yang","year":"2015","journal-title":"Front Microbiol"},{"key":"2023050300201654300_dkad059-B19","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1128\/JCM.37.6.1881-1884.1999","article-title":"Highly reproducible bactericidal activity test results by using a modified National Committee for Clinical Laboratory Standards broth macrodilution technique","volume":"37","author":"Hacek","year":"1999","journal-title":"J Clin Microbiol"},{"key":"2023050300201654300_dkad059-B20","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing\u2014Twenty-Sixth Edition: M100","author":"CLSI","year":"2016"},{"key":"2023050300201654300_dkad059-B21","doi-asserted-by":"crossref","first-page":"e02043-18","DOI":"10.1128\/AAC.02043-18","article-title":"ClyJ is a novel pneumococcal chimeric lysin with a cysteine- and histidine-dependent amidohydrolase\/peptidase catalytic domain","volume":"63","author":"Yang","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2023050300201654300_dkad059-B22","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1007\/s00253-019-10325-z","article-title":"Construction and characterization of a chimeric lysin ClyV with improved bactericidal activity against Streptococcus agalactiae in vitro and in vivo","volume":"104","author":"Huang","year":"2020","journal-title":"Appl Microbiol Biotechnol"},{"key":"2023050300201654300_dkad059-B23","doi-asserted-by":"crossref","first-page":"e1004109","DOI":"10.1371\/journal.ppat.1004109","article-title":"Structural and biochemical characterization reveals LysGH15 as an unprecedented \u201cEF-hand-like\u201d calcium-binding phage lysin","volume":"10","author":"Gu","year":"2014","journal-title":"PLoS Pathog"},{"key":"2023050300201654300_dkad059-B24","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/jac\/dkm524","article-title":"Plasma protein binding of fluoroquinolones affects antimicrobial activity","volume":"61","author":"Zeitlinger","year":"2008","journal-title":"J Antimicrob Chemother"},{"key":"2023050300201654300_dkad059-B25","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/cen.14362","article-title":"Measuring serum calcium: total, albumin-adjusted or ionized?","volume":"95","author":"Minisola","year":"2021","journal-title":"Clin Endocrinol"},{"key":"2023050300201654300_dkad059-B26","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/cen.14326","article-title":"Reference interval for albumin-adjusted calcium based on a large UK population","volume":"94","author":"Schini","year":"2021","journal-title":"Clin Endocrinol"},{"key":"2023050300201654300_dkad059-B27","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.copbio.2020.09.012","article-title":"Bacteriophage endolysins\u2014extending their application to tissues and the bloodstream","volume":"68","author":"Schmelcher","year":"2021","journal-title":"Curr Opin Biotechnol"},{"key":"2023050300201654300_dkad059-B28","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3390\/antibiotics10040461","article-title":"A highly active chimeric lysin with a calcium-enhanced bactericidal activity against Staphylococcus aureus in vitro and in vivo","volume":"10","author":"Li","year":"2021","journal-title":"Antibiotics"},{"key":"2023050300201654300_dkad059-B29","doi-asserted-by":"crossref","first-page":"7865","DOI":"10.1128\/JB.186.23.7865-7873.2004","article-title":"Teichoic acid is an essential polymer in Bacillus subtilis that is functionally distinct from teichuronic acid","volume":"186","author":"Bhavsar","year":"2004","journal-title":"J Bacteriol"},{"key":"2023050300201654300_dkad059-B30","doi-asserted-by":"crossref","first-page":"34391","DOI":"10.1074\/jbc.M111.244160","article-title":"Role of net charge on catalytic domain and influence of cell wall binding domain on bactericidal activity, specificity, and host range of phage lysins","volume":"286","author":"Low","year":"2011","journal-title":"J Biol Chem"},{"key":"2023050300201654300_dkad059-B31","doi-asserted-by":"crossref","first-page":"216","DOI":"10.3390\/microorganisms8020216","article-title":"Recombinant of the staphylococcal bacteriophage lysin CHAPk and its elimination against Streptococcus agalactiae biofilms","volume":"8","author":"Shan","year":"2020","journal-title":"Microorganisms"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/5\/1182\/50149048\/dkad059.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/5\/1182\/50149048\/dkad059.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:21:37Z","timestamp":1683073297000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/78\/5\/1182\/7075679"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,10]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3,10]]},"published-print":{"date-parts":[[2023,5,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkad059","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,5,3]]},"published":{"date-parts":[[2023,3,10]]}}}