{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T02:38:45Z","timestamp":1771036725594,"version":"3.50.1"},"reference-count":146,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,3,22]],"date-time":"2018-03-22T00:00:00Z","timestamp":1521676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Lytic enzymes encoded by bacteriophages have been intensively explored as alternative agents for combating bacterial pathogens in different contexts. The antibacterial character of these enzymes (enzybiotics) results from their degrading activity towards peptidoglycan, an essential component of the bacterial cell wall. In fact, phage lytic products have the capacity to kill target bacteria when added exogenously in the form of recombinant proteins. However, there is also growing recognition that the natural bactericidal activity of these agents can, and sometimes needs to be, substantially improved through manipulation of their functional domains or by equipping them with new functions. In addition, often, native lytic proteins exhibit features that restrict their applicability as effective antibacterials, such as poor solubility or reduced stability. Here, I present an overview of the engineering approaches that can be followed not only to overcome these and other restrictions, but also to generate completely new antibacterial agents with significantly enhanced characteristics. As conventional antibiotics are running short, the remarkable progress in this field opens up the possibility of tailoring efficient enzybiotics to tackle the most menacing bacterial infections.<\/jats:p>","DOI":"10.3390\/antibiotics7020029","type":"journal-article","created":{"date-parts":[[2018,3,22]],"date-time":"2018-03-22T14:39:31Z","timestamp":1521729571000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":129,"title":["Engineering of Phage-Derived Lytic Enzymes: Improving Their Potential as Antimicrobials"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4890-9446","authenticated-orcid":false,"given":"Carlos","family":"S\u00e3o-Jos\u00e9","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,22]]},"reference":[{"key":"ref_1","first-page":"277","article-title":"The antibiotic resistance crisis: Part 1: Causes and threats","volume":"40","author":"Ventola","year":"2015","journal-title":"Pharm. Ther."},{"key":"ref_2","unstructured":"WHO (2018, January 03). The World Is Running Out of Antibiotics, WHO Report Confirms. Available online: http:\/\/www.who.int\/mediacentre\/news\/releases\/2017\/running-out-antibiotics\/en\/."},{"key":"ref_3","unstructured":"O\u2019Neill, J. (2018, March 01). Tackling Drug-Restistant Infections Globally: Final Report and Recommendations. Available online: https:\/\/amr-review.org\/sites\/default\/files\/160525_Final%20paper_with%20cover.pdf."},{"key":"ref_4","unstructured":"Adeyi, O.O., Baris, E., Jonas, O.B., Irwin, A., Berthe, F.C.J., Le Gall, F.G., Marquez, P.V., Nikolic, I.A., Plante, C.A., and Schneidman, M. (2017). Drug-Resistant Infections: A Threat to Our Economic Future, World Bank Group. Final Report."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"j4339","DOI":"10.1136\/bmj.j4339","article-title":"Few novel antibiotics in the pipeline, WHO warns","volume":"358","author":"Kmietowicz","year":"2017","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S1473-3099(15)00466-1","article-title":"Alternatives to antibiotics-a pipeline portfolio review","volume":"16","author":"Czaplewski","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s40259-013-0081-y","article-title":"Bacteriophage polysaccharide depolymerases and biomedical applications","volume":"28","author":"Yan","year":"2014","journal-title":"BioDrugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.2174\/0929867322666150209152851","article-title":"Bacteriophages and phage-derived proteins\u2014Application approaches","volume":"22","author":"Maciejewska","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1007\/s00253-015-7247-0","article-title":"Bacteriophage-encoded depolymerases: Their diversity and biotechnological applications","volume":"100","author":"Pires","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1007\/s00253-017-8224-6","article-title":"Bacteriophage-encoded virion-associated enzymes to overcome the carbohydrate barriers during the infection process","volume":"101","author":"Latka","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1574-6976.2007.00094.x","article-title":"Peptidoglycan structure and architecture","volume":"32","author":"Vollmer","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1046\/j.1365-2958.2003.03894.x","article-title":"Peptidoglycan hydrolytic activities associated with bacteriophage virions","volume":"51","author":"Moak","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/1574-6976.12006","article-title":"Diversity in bacterial lysis systems: Bacteriophages show the way","volume":"37","author":"Gil","year":"2013","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_14","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. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/B978-0-12-394438-2.00007-4","article-title":"Endolysins as antimicrobials","volume":"83","author":"Nelson","year":"2012","journal-title":"Adv. Virus Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1099\/jmm.0.061028-0","article-title":"Lysins: The arrival of pathogen-directed anti-infectives","volume":"62","author":"Pastagia","year":"2013","journal-title":"J. Med. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e1062590","DOI":"10.1080\/21597081.2015.1062590","article-title":"Antimicrobial bacteriophage-derived proteins and therapeutic applications","volume":"5","author":"Roach","year":"2015","journal-title":"Bacteriophage"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Haddad Kashani, H., Schmelcher, M., Sabzalipoor, H., Seyed Hosseini, E., and Moniri, R. (2018). Recombinant endolysins as potential therapeutics against antibiotic-resistant Staphylococcus aureus: Current status of research and novel delivery strategies. Clin. Microbiol. Rev., 31.","DOI":"10.1128\/CMR.00071-17"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3109\/1040841X.2012.723675","article-title":"Bacteriophage virion-associated peptidoglycan hydrolases: Potential new enzybiotics","volume":"39","author":"Donovan","year":"2013","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.tifs.2012.06.016","article-title":"Bacteriophage endolysins as a response to emerging foodborne pathogens","volume":"28","author":"Oliveira","year":"2012","journal-title":"Trends Food Sci. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.copbio.2015.10.005","article-title":"Bacteriophage endolysins: Applications for food safety","volume":"37","author":"Schmelcher","year":"2016","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_22","first-page":"542","article-title":"Phage lytic proteins: Biotechnological applications beyond clinical antimicrobials","volume":"36","author":"Donovan","year":"2016","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gerstmans, H., Criel, B., and Briers, Y. (2017). Synthetic biology of modular endolysins. Biotechnol. Adv.","DOI":"10.1016\/j.biotechadv.2017.12.009"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e28281","DOI":"10.4161\/bact.28281","article-title":"Molecular architecture of tailed double-stranded DNA phages","volume":"4","author":"Fokine","year":"2014","journal-title":"Bacteriophage"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"E4919","DOI":"10.1073\/pnas.1501064112","article-title":"Structural remodeling of bacteriophage t4 and host membranes during infection initiation","volume":"112","author":"Hu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/978-1-4614-0980-9_5","article-title":"Contractile tail machines of bacteriophages","volume":"726","author":"Leiman","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Taylor, N.M.I., van Raaij, M.J., and Leiman, P.G. (2018). Contractile injection systems of bacteriophages and related systems. Mol. Microbiol.","DOI":"10.1111\/mmi.13921"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-1-4614-0980-9_6","article-title":"Long noncontractile tail machines of bacteriophages","volume":"726","author":"Davidson","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/mmi.12918","article-title":"The phage tail tape measure protein, an inner membrane protein and a periplasmic chaperone play connected roles in the genome injection process of E. coli phage HK97","volume":"96","author":"Cumby","year":"2015","journal-title":"Mol. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1126\/science.1231887","article-title":"The bacteriophage T7 virion undergoes extensive structural remodeling during infection","volume":"339","author":"Hu","year":"2013","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9552","DOI":"10.1073\/pnas.0803787105","article-title":"Crystal and cryoem structural studies of a cell wall degrading enzyme in the bacteriophage phi29 tail","volume":"105","author":"Xiang","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Xu, J., and Xiang, Y. (2017). Membrane penetration by bacterial viruses. J. Virol., 91.","DOI":"10.1128\/JVI.00162-17"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.mib.2013.08.008","article-title":"Phage lysis: Do we have the hole story yet?","volume":"16","author":"Young","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/mmi.12108","article-title":"Export of the pneumococcal phage SV1 lysin requires choline-containing teichoic acids and is holin-independent","volume":"87","author":"Frias","year":"2013","journal-title":"Mol. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s12275-014-4087-z","article-title":"Phage lysis: Three steps, three choices, one outcome","volume":"52","author":"Young","year":"2014","journal-title":"J. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/mmi.13448","article-title":"More than a hole: The holin lethal function may be required to fully sensitize bacteria to the lytic action of canonical endolysins","volume":"102","author":"Fernandes","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_37","unstructured":"Ghuysen, J.M., and Hakenbeck, R. (1994). Bacterial peptidoglycan: Overview and evolving concepts. Bacterial Cell Wall, Elsevier."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4558","DOI":"10.1128\/JVI.03277-12","article-title":"Molecular aspects and comparative genomics of bacteriophage endolysins","volume":"87","author":"Oliveira","year":"2013","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"D225","DOI":"10.1093\/nar\/gkq1189","article-title":"CDD: A conserved domain database for the functional annotation of proteins","volume":"39","author":"Lu","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"15847","DOI":"10.1074\/jbc.274.22.15847","article-title":"Multiple enzymatic activities of the murein hydrolase from staphylococcal phage \u03c611. Identification of a d-alanyl-glycine endopeptidase activity","volume":"274","author":"Navarre","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1099\/mic.0.27063-0","article-title":"The bifunctional peptidoglycan lysin of Streptococcus agalactiae bacteriophage B30","volume":"150","author":"Pritchard","year":"2004","journal-title":"Microbiology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10765","DOI":"10.1073\/pnas.0604521103","article-title":"Plyc: A multimeric bacteriophage lysin","volume":"103","author":"Nelson","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s00253-014-5930-1","article-title":"Biochemical and biophysical characterization of PlyGRCS, a bacteriophage endolysin active against methicillin-resistant Staphylococcus aureus","volume":"99","author":"Linden","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1038\/ncomms5269","article-title":"Molecular basis for bacterial peptidoglycan recognition by LysM domains","volume":"5","author":"Mesnage","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1128\/JB.188.7.2463-2472.2006","article-title":"Cross-linked peptidoglycan mediates lysostaphin binding to the cell wall envelope of Staphylococcus aureus","volume":"188","author":"Schneewind","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1111\/j.1365-2958.2011.07774.x","article-title":"The cell wall binding domain of listeria bacteriophage endolysin PlyP35 recognizes terminal GlcNac residues in cell wall teichoic acid","volume":"81","author":"Eugster","year":"2011","journal-title":"Mol. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1089\/mdr.1997.3.199","article-title":"The pneumococcal cell wall degrading enzymes: A modular design to create new lysins?","volume":"3","year":"1997","journal-title":"Microb. Drug Resist."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Payne, K.M., and Hatfull, G.F. (2012). Mycobacteriophage endolysins: Diverse and modular enzymes with multiple catalytic activities. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034052"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8125","DOI":"10.1073\/pnas.87.20.8125","article-title":"Chimeric phage-bacterial enzymes: A clue to the modular evolution of genes","volume":"87","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.2217\/fmb.12.97","article-title":"Bacteriophage endolysins as novel antimicrobials","volume":"7","author":"Schmelcher","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4975","DOI":"10.1128\/AEM.00446-16","article-title":"DUF3380 domain from a salmonella phage endolysin shows potent N-Acetylmuramidase activity","volume":"82","author":"Gerstmans","year":"2016","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"377","DOI":"10.2217\/fmb.15.8","article-title":"Breaking barriers: Expansion of the use of endolysins as novel antibacterials against Gram-negative bacteria","volume":"10","author":"Briers","year":"2015","journal-title":"Future Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"12752","DOI":"10.1073\/pnas.1208424109","article-title":"X-ray crystal structure of the streptococcal specific phage lysin PlyC","volume":"109","author":"McGowan","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/mmi.12857","article-title":"A two-component, multimeric endolysin encoded by a single gene","volume":"95","author":"Velours","year":"2015","journal-title":"Mol. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4882","DOI":"10.1074\/jbc.M115.671172","article-title":"Crystal structure of the CTP1L endolysin reveals how its activity is regulated by a secondary translation product","volume":"291","author":"Dunne","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1007\/s00018-004-4301-y","article-title":"Identification and characterization of a highly thermostable bacteriophage lysozyme","volume":"61","author":"Lavigne","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.bbrc.2008.07.102","article-title":"The structural peptidoglycan hydrolase gp181 of bacteriophage \u03c6kz","volume":"374","author":"Briers","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Paul, V.D., Rajagopalan, S.S., Sundarrajan, S., George, S.E., Asrani, J.Y., Pillai, R., Chikkamadaiah, R., Durgaiah, M., Sriram, B., and Padmanabhan, S. (2011). A novel bacteriophage tail-associated muralytic enzyme (TAME) from phage K and its development into a potent antistaphylococcal protein. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-226"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez, L., Mart\u00ednez, B., Zhou, Y., Rodr\u00edguez, A., Donovan, D.M., and Garc\u00eda, P. (2011). Lytic activity of the virion-associated peptidoglycan hydrolase HydH5 of Staphylococcus aureus bacteriophage vB_SauS-phiIPLA88. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-138"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1574-6968.2008.01152.x","article-title":"Tail-associated structural protein gp61 of Staphylococcus aureus phage \u03c6MR11 has bifunctional lytic activity","volume":"284","author":"Rashel","year":"2008","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6369","DOI":"10.1128\/AEM.01236-12","article-title":"The tape measure protein of the Staphylococcus aureus bacteriophage vB_SauS-phiIPLA35 has an active muramidase domain","volume":"78","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5137","DOI":"10.1007\/s00253-015-6483-7","article-title":"EC300: A phage-based, bacteriolysin-like protein with enhanced antibacterial activity against Enterococcus faecalis","volume":"99","author":"Leandro","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"542","DOI":"10.3389\/fmicb.2014.00542","article-title":"Engineered bacteriophage lysins as novel anti-infectives","volume":"5","author":"Yang","year":"2014","journal-title":"Front. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1111\/j.1365-2958.1993.tb01231.x","article-title":"Interchange of functional domains switches enzyme specificity: Construction of a chimeric pneumococcal-clostridial cell wall lytic enzyme","volume":"9","author":"Croux","year":"1993","journal-title":"Mol. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/j.1751-7915.2011.00263.x","article-title":"Domain shuffling and module engineering of Listeria phage endolysins for enhanced lytic activity and binding affinity","volume":"4","author":"Schmelcher","year":"2011","journal-title":"Microb. Biotechnol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7161","DOI":"10.1128\/JB.187.20.7161-7164.2005","article-title":"The recombinant phage lysin LysK has a broad spectrum of lytic activity against clinically relevant staphylococci, including methicillin-resistant Staphylococcus aureus","volume":"187","author":"Coffey","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1128\/AEM.07050-11","article-title":"Chimeric phage lysins act synergistically with lysostaphin to kill mastitis-causing Staphylococcus aureus in murine mammary glands","volume":"78","author":"Schmelcher","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"17257","DOI":"10.1038\/srep17257","article-title":"A chimeolysin with extended-spectrum streptococcal host range found by an induced lysis-based rapid screening method","volume":"5","author":"Yang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7436","DOI":"10.1128\/AAC.01872-16","article-title":"Antibiofilm activities of a novel chimeolysin against streptococcus mutans under physiological and cariogenic conditions","volume":"60","author":"Yang","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1093\/jac\/dkv038","article-title":"A novel chimeric phage lysin with high in vitro and in vivo bactericidal activity against Streptococcus pneumoniae","volume":"70","author":"Bustamante","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_72","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_73","first-page":"1156","article-title":"PL3 amidase, a tailor-made lysin constructed by domain shuffling with potent killing activity against pneumococci and related species","volume":"7","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1128\/AEM.07621-11","article-title":"Enhanced staphylolytic activity of the Staphylococcus aureus bacteriophage vB_SauS-phiIPLA88 HydH5 virion-associated peptidoglycan hydrolase: Fusions, deletions, and synergy with LysH5","volume":"78","author":"Donovan","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Rubio, L., Mart\u00ednez, B., Donovan, D.M., Garc\u00eda, P., and Rodr\u00edguez, A. (2013). Potential of the virion-associated peptidoglycan hydrolase HydH5 and its derivative fusion proteins in milk biopreservation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054828"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e02724-16","DOI":"10.1128\/AAC.02724-16","article-title":"Downregulation of autolysin-encoding genes by phage-derived lytic proteins inhibits biofilm formation in Staphylococcus aureus","volume":"61","author":"Campelo","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/alr.21680","article-title":"Fighting sinus-derived Staphylococcus aureus biofilms in vitro with a bacteriophage-derived muralytic enzyme","volume":"6","author":"Drilling","year":"2016","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e26564","DOI":"10.4161\/bact.26564","article-title":"Properties and mutation studies of a bacteriophage-derived chimeric recombinant staphylolytic protein P128: Comparison to recombinant lysostaphin","volume":"3","author":"Saravanan","year":"2013","journal-title":"Bacteriophage"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/1574-6968.12104","article-title":"Chimeric Ply187 endolysin kills Staphylococcus aureus more effectively than the parental enzyme","volume":"342","author":"Mao","year":"2013","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4621","DOI":"10.1128\/AAC.00126-14","article-title":"Intravitreal injection of the chimeric phage endolysin Ply187 protects mice from Staphylococcus aureus endophthalmitis","volume":"58","author":"Singh","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1128\/AAC.01625-09","article-title":"Synergism between a novel chimeric lysin and oxacillin protects against infection by methicillin-resistant Staphylococcus aureus","volume":"54","author":"Daniel","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1128\/AAC.00890-10","article-title":"A novel chimeric lysin shows superiority to mupirocin for skin decolonization of methicillin-resistant and -sensitive Staphylococcus aureus strains","volume":"55","author":"Pastagia","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1089\/mdr.2012.0025","article-title":"Novel chimerical endolysins with broad antimicrobial activity against methicillin-resistant Staphylococcus aureus","volume":"18","author":"Fernandes","year":"2012","journal-title":"Microb. Drug Resist."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.3390\/v7062758","article-title":"A thermophilic phage endolysin fusion to a Clostridium perfringens-specific cell wall binding domain creates an anti-Clostridium antimicrobial with improved thermostability","volume":"7","author":"Swift","year":"2015","journal-title":"Viruses"},{"key":"ref_85","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":"ref_86","doi-asserted-by":"crossref","first-page":"e02134-17","DOI":"10.1128\/AEM.02134-17","article-title":"Corrected and republished from: Identification of peptidoglycan hydrolase constructs with synergistic staphylolytic activity in cow\u2019s milk","volume":"84","author":"Verbree","year":"2018","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4452","DOI":"10.1128\/JB.181.15.4452-4460.1999","article-title":"Evidence for a holin-like protein gene fully embedded out of frame in the endolysin gene of Staphylococcus aureus bacteriophage 187","volume":"181","author":"Loessner","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6187","DOI":"10.1128\/AEM.01388-13","article-title":"The peptidoglycan hydrolase of Staphylococcus aureus bacteriophage 11 plays a structural role in the viral particle","volume":"79","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5174","DOI":"10.1073\/pnas.0501140102","article-title":"The complete genomes and proteomes of 27 Staphylococcus aureus bacteriophages","volume":"102","author":"Kwan","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1128\/AAC.01793-13","article-title":"Novel chimeric lysin with high-level antimicrobial activity against methicillin-resistant Staphylococcus aureus in vitro and in vivo","volume":"58","author":"Yang","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1080\/08927014.2014.905927","article-title":"Degradation of methicillin-resistant Staphylococcus aureus biofilms using a chimeric lysin","volume":"30","author":"Yang","year":"2014","journal-title":"Biofouling"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/1751-7915.12166","article-title":"Construction of a chimeric lysin Ply187N-V12C with extended lytic activity against staphylococci and streptococci","volume":"8","author":"Dong","year":"2015","journal-title":"Microb. Biotechnol."},{"key":"ref_93","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":"ref_94","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1128\/AEM.72.4.2988-2996.2006","article-title":"Peptidoglycan hydrolase fusions maintain their parental specificities","volume":"72","author":"Donovan","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_95","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":"ref_96","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.jmb.2006.11.056","article-title":"The 1.6 a crystal structure of the catalytic domain of PlyB, a bacteriophage lysin active against Bacillus anthracis","volume":"366","author":"Porter","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/femsle\/fnu019","article-title":"Lytic activity of the staphylolytic Twort phage endolysin CHAP domain is enhanced by the SH3b cell wall binding domain","volume":"362","author":"Becker","year":"2015","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12250-014-3535-6","article-title":"Molecular dissection of phage lysin PlySs2: Integrity of the catalytic and cell wall binding domains is essential for its broad lytic activity","volume":"30","author":"Huang","year":"2015","journal-title":"Virol. Sin."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3685","DOI":"10.1128\/AEM.07884-11","article-title":"Genomic sequence of bacteriophage ATCC 8074-B1 and activity of its endolysin and engineered variants against Clostridium sporogenes","volume":"78","author":"Mayer","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1128\/AEM.01831-08","article-title":"Phage lysin LysK can be truncated to its CHAP domain and retain lytic activity against live antibiotic-resistant staphylococci","volume":"75","author":"Horgan","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5108","DOI":"10.1128\/AEM.03065-05","article-title":"The cell lysis activity of the Streptococcus agalactiae bacteriophage B30 endolysin relies on the cysteine, histidine-dependent amidohydrolase\/peptidase domain","volume":"72","author":"Donovan","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"625341","DOI":"10.1155\/2013\/625341","article-title":"Bacteriophage-derived peptidase CHAPK eliminates and prevents staphylococcal biofilms","volume":"2013","author":"Fenton","year":"2013","journal-title":"Int. J. Microbiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"404","DOI":"10.4161\/bbug.1.6.13422","article-title":"The truncated phage lysin CHAPK eliminates Staphylococcus aureus in the nares of mice","volume":"1","author":"Fenton","year":"2010","journal-title":"Bioeng. Bugs"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1574-6968.2009.01541.x","article-title":"LysK CHAP endopeptidase domain is required for lysis of live staphylococcal cells","volume":"294","author":"Becker","year":"2009","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1128\/AEM.01616-06","article-title":"Lytic activity of recombinant bacteriophage \u03c611 and \u03c612 endolysins on whole cells and biofilms of Staphylococcus aureus","volume":"73","author":"Sass","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Bene\u0161\u00edk, M., Nov\u00e1\u010dek, J., Janda, L., Dopitov\u00e1, R., Pernisov\u00e1, M., Melkov\u00e1, K., Ti\u0161\u00e1kov\u00e1, L., Do\u0161ka\u0159, J., \u017d\u00eddek, L., and Hej\u00e1tko, J. (2017). Role of SH3b binding domain in a natural deletion mutant of Kayvirus endolysin LysF1 with a broad range of lytic activity. Virus Genes.","DOI":"10.1007\/s11262-017-1507-2"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.rvsc.2017.02.011","article-title":"The lytic activity of recombinant phage lysin LysK\u0394amidase against staphylococcal strains associated with bovine and human infections in the Jiangsu province of China","volume":"111","author":"Zhou","year":"2017","journal-title":"Res. Vet. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"35433","DOI":"10.1074\/jbc.M502723200","article-title":"Structure and lytic activity of a Bacillus anthracis prophage endolysin","volume":"280","author":"Low","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1128\/JB.00439-11","article-title":"Structure-based modification of a Clostridium difficile-targeting endolysin affects activity and host range","volume":"193","author":"Mayer","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1007\/s00253-006-0771-1","article-title":"Mutagenesis of a bacteriophage lytic enzyme PlyGBS significantly increases its antibacterial activity against group B streptococci","volume":"74","author":"Cheng","year":"2007","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1574-6968.2008.01287.x","article-title":"LambdaSa2 prophage endolysin requires Cpl-7-binding domains and amidase-5 domain for antimicrobial lysis of streptococci","volume":"287","author":"Donovan","year":"2008","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Heselpoth, R.D., and Nelson, D.C. (2012). A new screening method for the directed evolution of thermostable bacteriolytic enzymes. J. Vis. Exp., 4216.","DOI":"10.3791\/4216-v"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5355","DOI":"10.1128\/AAC.01372-13","article-title":"Improving the lethal effect of Cpl-7, a pneumococcal phage lysozyme with broad bactericidal activity, by inverting the net charge of its cell wall-binding module","volume":"57","author":"Bustamante","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/protein\/gzv004","article-title":"Increasing the stability of the bacteriophage endolysin plyc using rationale-based foldx computational modeling","volume":"28","author":"Heselpoth","year":"2015","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.ijantimicag.2011.08.009","article-title":"A stable phage lysin (Cpl-1) dimer with increased antipneumococcal activity and decreased plasma clearance","volume":"38","author":"Resch","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_116","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":"ref_117","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3389\/fcimb.2017.00290","article-title":"A novel chimeric endolysin with antibacterial activity against methicillin-resistant Staphylococcus aureus","volume":"7","author":"Fahimi","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"12085","DOI":"10.1074\/jbc.M113.529594","article-title":"Molecular dissection of phage endolysin: An interdomain interaction confers host specificity in Lysin A of Mycobacterium phage D29","volume":"289","author":"Pohane","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"7447","DOI":"10.1128\/AAC.01357-15","article-title":"Using a novel lysin to help control Clostridium difficile infections","volume":"59","author":"Wang","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.bcp.2016.09.018","article-title":"Antimicrobial peptides (AMPS): Ancient compounds that represent novel weapons in the fight against bacteria","volume":"133","author":"Ageitos","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mib.2016.05.006","article-title":"Cell wall hydrolases and antibiotics: Exploiting synergy to create efficacious new antimicrobial treatments","volume":"33","author":"Wittekind","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.copbio.2011.06.012","article-title":"Strategies for extended serum half-life of protein therapeutics","volume":"22","author":"Kontermann","year":"2011","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2165\/00063030-200822050-00004","article-title":"The impact of PEGylation on biological therapies","volume":"22","author":"Veronese","year":"2008","journal-title":"BioDrugs"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1128\/AAC.47.2.554-558.2003","article-title":"Improved pharmacokinetics and reduced antibody reactivity of lysostaphin conjugated to polyethylene glycol","volume":"47","author":"Walsh","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.biochi.2013.04.013","article-title":"Physicochemical characterization of the staphylolytic LysK enzyme in complexes with polycationic polymers as a potent antimicrobial","volume":"95","author":"Filatova","year":"2013","journal-title":"Biochimie"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/2191-0855-1-29","article-title":"PEGylating a bacteriophage endolysin inhibits its bactericidal activity","volume":"1","author":"Resch","year":"2011","journal-title":"AMB Express"},{"key":"ref_127","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":"ref_128","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Rubio, L., Mart\u00ednez, B., Rodr\u00edguez, A., Donovan, D.M., G\u00f6tz, F., and Garc\u00eda, P. (2013). The phage lytic proteins from the Staphylococcus aureus bacteriophage vB_SauS-phiIPLA88 display multiple active catalytic domains and do not trigger staphylococcal resistance. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064671"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1128\/AAC.02972-15","article-title":"Novel engineered peptides of a phage lysin as effective antimicrobials against multidrug-resistant Acinetobacter baumannii","volume":"60","author":"Thandar","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"11477","DOI":"10.1038\/s41598-017-11832-7","article-title":"Highly potent antimicrobial modified peptides derived from the Acinetobacter baumannii phage endolysin LysAB2","volume":"7","author":"Peng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"9857","DOI":"10.1073\/pnas.1203472109","article-title":"Structural engineering of a phage lysin that targets Gram-negative pathogens","volume":"109","author":"Lukacik","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1007\/s10482-017-0912-9","article-title":"The N-terminal and central domain of colicin A enables phage lysin to lyse Escherichia coli extracellularly","volume":"110","author":"Yan","year":"2017","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e01379-14","DOI":"10.1128\/mBio.01379-14","article-title":"Engineered endolysin-based \u201cArtilysins\u201d to combat multidrug-resistant gram-negative pathogens","volume":"5","author":"Briers","year":"2014","journal-title":"mBio"},{"key":"ref_134","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_135","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1128\/AAC.00285-16","article-title":"Efficacy of artilysin art-175 against resistant and persistent Acinetobacter baumannii","volume":"60","author":"Defraine","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Schirmeier, E., Zimmermann, P., Hofmann, V., Biebl, M., Gerstmans, H., Maervoet, V.E., and Briers, Y. (2017). Inhibitory and bactericidal effect of Artilysin\u00ae Art-175 against colistin-resistant mcr-1-positive Escherichia coli isolates. Int. J. Antimicrob. Agents.","DOI":"10.1016\/j.ijantimicag.2017.08.027"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s12275-017-6431-6","article-title":"The antibacterial activity of E. coli bacteriophage lysin lysep3 is enhanced by fusing the Bacillus amyloliquefaciens bacteriophage endolysin binding domain D8 to the C-terminal region","volume":"55","author":"Wang","year":"2017","journal-title":"J. Microbiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s10482-016-0806-2","article-title":"Enhancement of the direct antimicrobial activity of Lysep3 against Escherichia coli by inserting cationic peptides into its C-terminus","volume":"110","author":"Ma","year":"2017","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"8985","DOI":"10.1074\/jbc.M109.078725","article-title":"Outer membrane protein I of Pseudomonas aeruginosa is a target of cationic antimicrobial peptide\/protein","volume":"285","author":"Lin","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_140","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":"ref_141","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s00253-003-1522-1","article-title":"Bacillus amyloliquefaciens phage endolysin can enhance permeability of Pseudomonas aeruginosa outer membrane and induce cell lysis","volume":"65","author":"Orito","year":"2004","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"35382","DOI":"10.1038\/srep35382","article-title":"\u2018Artilysation\u2019 of endolysin \u03bbSa2lys strongly improves its enzymatic and antibacterial activity against streptococci","volume":"6","author":"Chang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3389\/fmicb.2012.00071","article-title":"Classical labeling of bacterial pathogens according to their lifestyle in the host: Inconsistencies and alternatives","volume":"3","author":"Silva","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.mehy.2009.07.006","article-title":"Fusion to cell-penetrating peptides will enable lytic enzymes to kill intracellular bacteria","volume":"74","author":"Borysowski","year":"2010","journal-title":"Med. Hypotheses"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2174\/138920110790909731","article-title":"Cell-penetrating peptide technology to deliver chaperones and associated factors in diseases and basic research","volume":"11","author":"Dietz","year":"2010","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e13152","DOI":"10.7554\/eLife.13152","article-title":"A bacteriophage endolysin that eliminates intracellular streptococci","volume":"5","author":"Shen","year":"2016","journal-title":"eLife"}],"updated-by":[{"DOI":"10.3390\/antibiotics7030056","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,3,22]],"date-time":"2018-03-22T00:00:00Z","timestamp":1521676800000}}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/7\/2\/29\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T23:15:41Z","timestamp":1754262941000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/7\/2\/29"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,22]]},"references-count":146,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,6]]}},"alternative-id":["antibiotics7020029"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics7020029","relation":{"correction":[{"id-type":"doi","id":"10.3390\/antibiotics7030056","asserted-by":"object"}]},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,22]]}}}