{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T16:51:09Z","timestamp":1793465469775,"version":"4.5.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007173","name":"NARO | Bio-oriented Technology Research Advancement Institution","doi-asserted-by":"publisher","award":["JPJ011937"],"award-info":[{"award-number":["JPJ011937"]}],"id":[{"id":"10.13039\/501100007173","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Antibiot"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Global concerns about drug-resistant bacteria have underscored the need for new antimicrobial drugs. Emerging strategies in drug discovery include considering the third factors that influence drug activity. These factors include host-derived elements, adjuvants, and drug combinations, which are crucial in regulating antimicrobial efficacy. Traditional in vivo assessments have relied on animal models to study drug absorption, distribution, metabolism, excretion, and toxicity (ADMET). Alternative models, such as silkworms, are being explored to overcome the ethical and financial barriers associated with mammalian models. The silkworm has been proven effective in evaluating ADMET and in highlighting the therapeutic potential enhanced by third factors. Host factors (either mammalian or non-mammalian) enhance the antimicrobial activity of antimicrobial agents such as lysocin E. Additionally, using <jats:sc>d<\/jats:sc>-cycloserine to potentiate vancomycin has successfully combated vancomycin-resistant infections in silkworms. Leveraging silkworms in drug discovery could establish a novel screening method incorporating interactions with third factors, whether host related or non-host-related, thus promising new pathways for identifying antimicrobial drugs with unique mechanisms of action.<\/jats:p>","DOI":"10.1038\/s41429-024-00788-2","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T11:55:37Z","timestamp":1731585337000},"page":"69-77","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Discovery of new AMR drugs targeting modulators of antimicrobial activity using in vivo silkworm screening systems"],"prefix":"10.1038","volume":"78","author":[{"given":"Fumiaki","family":"Tabuchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Mikami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Miyauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2849-8432","authenticated-orcid":false,"given":"Kazuhisa","family":"Sekimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9076-0569","authenticated-orcid":false,"given":"Atsushi","family":"Miyashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"788_CR1","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3390\/antibiotics11020182","volume":"11","author":"K Iskandar","year":"2022","unstructured":"Iskandar K, Murugaiyan J, Hammoudi Halat D, Hage SE, Chibabhai V, Adukkadukkam S, et al. Antibiotic discovery and resistance: the chase and the race. Antibiotics. 2022;11:182.","journal-title":"Antibiotics"},{"key":"788_CR2","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/s41570-021-00313-1","volume":"5","author":"M Miethke","year":"2021","unstructured":"Miethke M, Pieroni M, Weber T, Br\u00f6nstrup M, Hammann P, Halby L, et al. Towards the sustainable discovery and development of new antibiotics. Nat Rev Chem. 2021;5:726\u201349.","journal-title":"Nat Rev Chem"},{"key":"788_CR3","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1038\/ja.2017.124","volume":"70","author":"VL Simpkin","year":"2017","unstructured":"Simpkin VL, Renwick MJ, Kelly R, Mossialos E. Incentivising innovation in antibiotic drug discovery and development: progress, challenges and next steps. J Antibiotics. 2017;70:1087\u201396.","journal-title":"J Antibiotics"},{"key":"788_CR4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26702-0","volume":"12","author":"H Hamamoto","year":"2021","unstructured":"Hamamoto H, Panthee S, Paudel A, Ishii K, Yasukawa J, Su J, et al. Serum apolipoprotein A-I potentiates the therapeutic efficacy of lysocin E against Staphylococcus aureus. Nat Commun. 2021;12:6364.","journal-title":"Nat Commun"},{"key":"788_CR5","doi-asserted-by":"publisher","first-page":"e1007697","DOI":"10.1371\/journal.ppat.1007697","volume":"15","author":"A Crabb\u00e9","year":"2019","unstructured":"Crabb\u00e9 A, Ostyn L, Staelens S, Rigauts C, Risseeuw M, Dhaenens M, et al. Host metabolites stimulate the bacterial proton motive force to enhance the activity of aminoglycoside antibiotics. PLoS Pathog. 2019;15:e1007697.","journal-title":"PLoS Pathog"},{"key":"788_CR6","first-page":"349","volume":"4","author":"T Fujiyuki","year":"2010","unstructured":"Fujiyuki T, Imamura K, Hamamoto H, Sekimizu K. Evaluation of therapeutic effects and pharmacokinetics of antibacterial chromogenic agents in a silkworm model of Staphylococcus aureus infection. Drug Discov Ther. 2010;4:349\u201354.","journal-title":"Drug Discov Ther"},{"key":"788_CR7","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.bcp.2016.10.005","volume":"133","author":"\u00c7 Y\u0131lmaz","year":"2017","unstructured":"Y\u0131lmaz \u00c7, \u00d6zcengiz G. Antibiotics: Pharmacokinetics, toxicity, resistance and multidrug efflux pumps. Biochem Pharmacol. 2017;133:43\u201362.","journal-title":"Biochem Pharmacol"},{"key":"788_CR8","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1345\/aph.1D156","volume":"38","author":"M Adra","year":"2004","unstructured":"Adra M, Lawrence KR. Trimethoprim\/sulfamethoxazole for treatment of Severe Staphylococcus aureus infections. Ann Pharmacother. 2004;38:338\u201341.","journal-title":"Ann Pharmacother"},{"key":"788_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1586\/eri.09.117","volume":"8","author":"O Sk\u00f6ld","year":"2010","unstructured":"Sk\u00f6ld O. Sulfonamides and trimethoprim. Expert Rev Anti Infect Ther. 2010;8:1\u20136.","journal-title":"Expert Rev Anti Infect Ther"},{"key":"788_CR10","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1128\/AAC.40.9.2147","volume":"40","author":"C Darras-Joly","year":"1996","unstructured":"Darras-Joly C, B\u00e9dos JP, Sauve C, Moine P, Vall\u00e9e E, Carbon C, et al. Synergy between amoxicillin and gentamicin in combination against a highly penicillin-resistant and -tolerant strain of Streptococcus pneumoniae in a mouse pneumonia model. Antimicrob Agents Chemother. 1996;40:2147\u201351.","journal-title":"Antimicrob Agents Chemother"},{"key":"788_CR11","doi-asserted-by":"crossref","unstructured":"Brennan-Krohn T, Pironti A, Kirby JE. Synergistic activity of colistin-containing combinations against colistin-resistant enterobacteriaceae. Antimicrob Agents Chemother. 2018;62:e00873\u201318.","DOI":"10.1128\/AAC.00873-18"},{"key":"788_CR12","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/nchembio.1710","volume":"11","author":"H Hamamoto","year":"2015","unstructured":"Hamamoto H, Urai M, Ishii K, Yasukawa J, Paudel A, Murai M, et al. Lysocin E is a new antibiotic that targets menaquinone in the bacterial membrane. Nat Chem Biol. 2015;11:127\u201333.","journal-title":"Nat Chem Biol"},{"key":"788_CR13","doi-asserted-by":"publisher","first-page":"4910","DOI":"10.7150\/thno.56205","volume":"11","author":"Y Liu","year":"2021","unstructured":"Liu Y, Tong Z, Shi J, Li R, Upton M, Wang Z. Drug repurposing for next-generation combination therapies against multidrug-resistant bacteria. Theranostics. 2021;11:4910\u201328.","journal-title":"Theranostics"},{"key":"788_CR14","doi-asserted-by":"publisher","first-page":"i3","DOI":"10.1093\/jac\/dkh050","volume":"53","author":"AR White","year":"2004","unstructured":"White AR, Kaye C, Poupard J, Pypstra R, Woodnutt G, Wynne B. Augmentin (amoxicillin\/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent. J Antimicrob Chemother. 2004;53:i3\u201320.","journal-title":"J Antimicrob Chemother"},{"key":"788_CR15","doi-asserted-by":"publisher","first-page":"6970","DOI":"10.1128\/AAC.03672-14","volume":"58","author":"DJ Hess","year":"2014","unstructured":"Hess DJ, Henry-Stanley MJ, Wells CL. Antibacterial synergy of glycerol monolaurate and aminoglycosides in Staphylococcus aureus biofilms. Antimicrob Agents Chemother. 2014;58:6970\u20133.","journal-title":"Antimicrob Agents Chemother"},{"key":"788_CR16","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/nchembio.559","volume":"7","author":"L Ejim","year":"2011","unstructured":"Ejim L, Farha MA, Falconer SB, Wildenhain J, Coombes BK, Tyers M, et al. Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial efficacy. Nat Chem Biol. 2011;7:348\u201350.","journal-title":"Nat Chem Biol"},{"key":"788_CR17","doi-asserted-by":"publisher","first-page":"14570","DOI":"10.1073\/pnas.0903619106","volume":"106","author":"S Lee","year":"2009","unstructured":"Lee S, Hinz A, Bauerle E, Angermeyer A, Juhaszova K, Kaneko Y, et al. Targeting a bacterial stress response to enhance antibiotic action. Proc Natl Acad Sci USA. 2009;106:14570\u20135.","journal-title":"Proc Natl Acad Sci USA"},{"key":"788_CR18","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.3390\/biomedicines11051448","volume":"11","author":"MF Varela","year":"2023","unstructured":"Varela MF, Stephen J, Bharti D, Lekshmi M, Kumar S. Inhibition of multidrug efflux pumps belonging to the major facilitator superfamily in bacterial pathogens. Biomedicines. 2023;11:1448.","journal-title":"Biomedicines"},{"key":"788_CR19","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/ja.2014.83","volume":"68","author":"JA Perry","year":"2015","unstructured":"Perry JA, Koteva K, Verschoor CP, Wang W, Bowdish DM, Wright GD. A macrophage-stimulating compound from a screen of microbial natural products. J Antibiot (Tokyo). 2015;68:40\u201346.","journal-title":"J Antibiot (Tokyo)"},{"key":"788_CR20","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202300472","volume":"10","author":"JT Mhlongo","year":"2023","unstructured":"Mhlongo JT, Waddad AY, Albericio F, de la Torre BG. Antimicrobial peptide synergies for fighting infectious diseases. Adv Sci. 2023;10:2300472.","journal-title":"Adv Sci"},{"key":"788_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1363441","volume":"15","author":"J Li","year":"2024","unstructured":"Li J, Han N, Li Y, Zhao F, Xiong W, Zeng Z. The synergistic antibacterial activity and mechanism of colistin-oxethazaine combination against gram-negative pathogens. Front Pharm. 2024;15:1363441.","journal-title":"Front Pharm"},{"key":"788_CR22","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.jmii.2015.10.010","volume":"50","author":"W Wei","year":"2017","unstructured":"Wei W, Yang H, Hu L, Ye Y, Li J. Activity of levofloxacin in combination with colistin against Acinetobacter baumannii: In vitro and in a Galleria mellonella model. J Microbiol, Immunol Infect. 2017;50:821\u201330.","journal-title":"J Microbiol, Immunol Infect"},{"key":"788_CR23","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1006\/mpat.2002.0494","volume":"32","author":"C Kaito","year":"2002","unstructured":"Kaito C, Akimitsu N, Watanabe H, Sekimizu K. Silkworm larvae as an animal model of bacterial infection pathogenic to humans. Microb Pathogenesis. 2002;32:183\u201390.","journal-title":"Microb Pathogenesis"},{"key":"788_CR24","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1128\/AAC.48.3.774-779.2004","volume":"48","author":"H Hamamoto","year":"2004","unstructured":"Hamamoto H, Kurokawa K, Kaito C, Kamura K, Manitra Razanajatovo I, Kusuhara H, et al. Quantitative evaluation of the therapeutic effects of antibiotics using silkworms infected with human pathogenic microorganisms. Antimicrobial agents Chemother. 2004;48:774\u20139.","journal-title":"Antimicrobial agents Chemother"},{"key":"788_CR25","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1574-6968.2012.02599.x","volume":"333","author":"A Miyashita","year":"2012","unstructured":"Miyashita A, Iyoda S, Ishii K, Hamamoto H, Sekimizu K, Kaito C. Lipopolysaccharide O-antigen of enterohemorrhagic Escherichia coli O157:H7 is required for killing both insects and mammals. FEMS Microbiol Lett. 2012;333:59\u201368.","journal-title":"FEMS Microbiol Lett"},{"key":"788_CR26","doi-asserted-by":"publisher","first-page":"14412","DOI":"10.1074\/jbc.M113.525139","volume":"289","author":"A Miyashita","year":"2014","unstructured":"Miyashita A, Kizaki H, Kawasaki K, Sekimizu K, Kaito C. Primed immune responses to gram-negative peptidoglycans confer infection resistance in silkworms. J Biol Chem. 2014;289:14412\u201321.","journal-title":"J Biol Chem"},{"key":"788_CR27","doi-asserted-by":"publisher","first-page":"e0130486","DOI":"10.1371\/journal.pone.0130486","volume":"10","author":"A Miyashita","year":"2015","unstructured":"Miyashita A, Takahashi S, Ishii K, Sekimizu K, Kaito C. Primed immune responses triggered by ingested bacteria lead to systemic infection tolerance in silkworms. PLoS One. 2015;10:e0130486.","journal-title":"PLoS One"},{"key":"788_CR28","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/ja.2016.106","volume":"70","author":"I Nakamura","year":"2017","unstructured":"Nakamura I, Kanasaki R, Yoshikawa K, Furukawa S, Fujie A, Hamamoto H, et al. Discovery of a new antifungal agent ASP2397 using a silkworm model of Aspergillus fumigatus infection. J Antibiotics. 2017;70:41\u201344.","journal-title":"J Antibiotics"},{"key":"788_CR29","doi-asserted-by":"publisher","first-page":"373","DOI":"10.3389\/fmicb.2017.00373","volume":"8","author":"S Panthee","year":"2017","unstructured":"Panthee S, Paudel A, Hamamoto H, Sekimizu K. Advantages of the silkworm as an animal model for developing novel antimicrobial agents. Front Microbiol. 2017;8:373.","journal-title":"Front Microbiol"},{"key":"788_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46013-1","volume":"9","author":"H Hamamoto","year":"2019","unstructured":"Hamamoto H, Horie R, Sekimizu K. Pharmacokinetics of anti-infectious reagents in silkworms. Sci Rep. 2019;9:9451.","journal-title":"Sci Rep."},{"key":"788_CR31","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/1348-0421.12668","volume":"63","author":"Y Matsumoto","year":"2019","unstructured":"Matsumoto Y, Sekimizu K. Silkworm as an experimental animal for research on fungal infections. Microbiol Immunol. 2019;63:41\u201350.","journal-title":"Microbiol Immunol"},{"key":"788_CR32","doi-asserted-by":"publisher","first-page":"73","DOI":"10.5582\/ddt.2021.01035","volume":"15","author":"K Mikami","year":"2021","unstructured":"Mikami K, Sonobe K, Ishino K, Noda T, Kato M, Hanao M, et al. Evaluation of pathogenicity and therapeutic effectiveness of antibiotics using silkworm Nocardia infection model. Drug Discoveries Therapeutics. 2021;15:73\u201377.","journal-title":"Drug Discoveries Therapeutics"},{"key":"788_CR33","doi-asserted-by":"publisher","first-page":"139","DOI":"10.5582\/ddt.2021.01041","volume":"15","author":"A Miyashita","year":"2021","unstructured":"Miyashita A, Hamamoto H, Sekimizu K. Applying the silkworm model for the search of immunosuppressants. Drug Discoveries Therapeutics. 2021;15:139\u201342.","journal-title":"Drug Discoveries Therapeutics"},{"key":"788_CR34","doi-asserted-by":"publisher","first-page":"51","DOI":"10.5582\/ddt.2021.01020","volume":"15","author":"A Miyashita","year":"2021","unstructured":"Miyashita A, Sekimizu K. Using silkworms to search for lactic acid bacteria that contribute to infection prevention and improvement of hyperglycemia. Drug Discoveries Therapeutics. 2021;15:51\u201354.","journal-title":"Drug Discoveries Therapeutics"},{"key":"788_CR35","first-page":"334","volume":"149","author":"H Hamamoto","year":"2009","unstructured":"Hamamoto H, Tonoike A, Narushima K, Horie R, Sekimizu K. Silkworm as a model animal to evaluate drug candidate toxicity and metabolism. Comp Biochem Physiol Part C: Toxicol Pharmacol. 2009;149:334\u20139.","journal-title":"Comp Biochem Physiol Part C: Toxicol Pharmacol"},{"key":"788_CR36","unstructured":"Orlans FB Research on Animals, Law, Legislative, and Welfare Issues in the Use of Animals for Genetic Engineering and Xenotransplantation. Encyclopedia of Ethical, Legal and Policy Issues in Biotechnology."},{"key":"788_CR37","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/ja.2010.9","volume":"63","author":"R Uchida","year":"2010","unstructured":"Uchida R, Iwatsuki M, Kim Y-P, Ohte S, \u014cmura S, Tomoda H. Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. I: Fermentation, isolation and biological properties. J Antibiotics. 2010;63:151\u20135.","journal-title":"J Antibiotics"},{"key":"788_CR38","doi-asserted-by":"publisher","first-page":"249","DOI":"10.5582\/ddt.2014.01050","volume":"8","author":"R Uchida","year":"2014","unstructured":"Uchida R, Hanaki H, Matsui H, Hamamoto H, Sekimizu K, Iwatsuki M, et al. In vitro and in vivo anti-MRSA activities of nosokomycins. Drug Discoveries Therapeutics. 2014;8:249\u201354.","journal-title":"Drug Discoveries Therapeutics"},{"key":"788_CR39","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1248\/cpb.c15-00743","volume":"64","author":"H Tomoda","year":"2016","unstructured":"Tomoda H. New approaches to drug discovery for combating MRSA. Chem Pharm Bull. 2016;64:104\u201311.","journal-title":"Chem Pharm Bull"},{"key":"788_CR40","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1039\/c001461n","volume":"27","author":"B Ostash","year":"2010","unstructured":"Ostash B, Walker S. Moenomycin family antibiotics: chemical synthesis, biosynthesis, and biological activity. Nat Prod Rep. 2010;27:1594\u2013617.","journal-title":"Nat Prod Rep."},{"key":"788_CR41","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1126\/science.1136611","volume":"315","author":"AL Lovering","year":"2007","unstructured":"Lovering AL, de Castro LH, Lim D, Strynadka NC. Structural insight into the transglycosylation step of bacterial cell-wall biosynthesis. Science. 2007;315:1402\u20135.","journal-title":"Science"},{"key":"788_CR42","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/ja.2016.107","volume":"70","author":"I Nakamura","year":"2017","unstructured":"Nakamura I, Yoshimura S, Masaki T, Takase S, Ohsumi K, Hashimoto M, et al. ASP2397: a novel antifungal agent produced by Acremonium persicinum MF-347833. J Antibiotics. 2017;70:45\u201351.","journal-title":"J Antibiotics"},{"key":"788_CR43","doi-asserted-by":"publisher","first-page":"02689","DOI":"10.1128\/aac","volume":"63","author":"I Nakamura","year":"2019","unstructured":"Nakamura I, Ohsumi K, Takeda S, Katsumata K, Matsumoto S, Akamatsu S, et al. ASP2397 is a novel natural compound that exhibits rapid and potent fungicidal activity against Aspergillus species through a specific transporter. Antimicrobial agents Chemother. 2019;63:02689\u201302618. https:\/\/doi.org\/10.1128\/aac.","journal-title":"Antimicrobial agents Chemother"},{"key":"788_CR44","doi-asserted-by":"crossref","unstructured":"Kan WC, Chen YC, Wu VC, Shiao CC. Vancomycin-associated acute kidney injury: a narrative review from pathophysiology to clinical application. Int J Mol Sci. 2022;23.","DOI":"10.3390\/ijms23042052"},{"issue":"Suppl 1","key":"788_CR45","doi-asserted-by":"publisher","first-page":"S35","DOI":"10.1086\/491712","volume":"42","author":"MJ Rybak","year":"2006","unstructured":"Rybak MJ. The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin Infect Dis. 2006;42(Suppl 1):S35\u201339.","journal-title":"Clin Infect Dis"},{"key":"788_CR46","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlad157","volume":"6","author":"V Venugopalan","year":"2024","unstructured":"Venugopalan V, Maranchick N, Hanai D, Hernandez YJ, Joseph Y, Gore A, et al. Association of piperacillin and vancomycin exposure on acute kidney injury during combination therapy. JAC Antimicrob Resist. 2024;6:dlad157.","journal-title":"JAC Antimicrob Resist"},{"key":"788_CR47","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.2165\/00003495-200363140-00006","volume":"63","author":"N Lee","year":"2003","unstructured":"Lee N, Yuen KY, Kumana CR. Clinical role of beta-lactam\/beta-lactamase inhibitor combinations. Drugs. 2003;63:1511\u201324.","journal-title":"Drugs"},{"key":"788_CR48","doi-asserted-by":"publisher","first-page":"57","DOI":"10.5582\/ddt.2016.01025","volume":"10","author":"K Usui","year":"2016","unstructured":"Usui K, Nishida S, Sugita T, Ueki T, Matsumoto Y, Okumura H, et al. Acute oral toxicity test of chemical compounds in silkworms. Drug Discoveries Therapeutics. 2016;10:57\u201361.","journal-title":"Drug Discoveries Therapeutics"},{"key":"788_CR49","doi-asserted-by":"publisher","first-page":"4131","DOI":"10.3390\/molecules28104131","volume":"28","author":"G Wu","year":"2023","unstructured":"Wu G, Jiang L, Guo J, Li W, Ma L, Tang B, et al. The study of alanine transaminase activity in tissues of silkworm (bombyx mori) via direct analysis in real-time (DART) mass spectrometry. Molecules. 2023;28:4131.","journal-title":"Molecules"},{"key":"788_CR50","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1007\/s10528-021-10046-x","volume":"59","author":"SH Prabhuling","year":"2021","unstructured":"Prabhuling SH, Makwana P, Pradeep ANR, Vijayan K, Mishra RK. Release of mediator enzyme \u03b2-hexosaminidase and modulated gene expression accompany hemocyte degranulation in response to parasitism in the silkworm Bombyx mori. Biochem Genet. 2021;59:997\u20131017.","journal-title":"Biochem Genet"},{"key":"788_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/srep17092","volume":"5","author":"K Ishii","year":"2015","unstructured":"Ishii K, Tabuchi F, Matsuo M, Tatsuno K, Sato T, Okazaki M, et al. Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis. Sci Rep. 2015;5:17092.","journal-title":"Sci Rep."},{"key":"788_CR52","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/ja.2017.7","volume":"70","author":"F Tabuchi","year":"2017","unstructured":"Tabuchi F, Matsumoto Y, Ishii M, Tatsuno K, Okazaki M, Sato T, et al. Synergistic effects of vancomycin and \u03b2-lactams against vancomycin highly resistant Staphylococcus aureus. J Antibiotics. 2017;70:771\u20134.","journal-title":"J Antibiotics"},{"key":"788_CR53","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1128\/AAC.00348-09","volume":"54","author":"C Joukhadar","year":"2010","unstructured":"Joukhadar C, Pillai S, Wennersten C, Moellering RC Jr., Eliopoulos GM. Lack of bactericidal antagonism or synergism in vitro between oxacillin and vancomycin against methicillin-susceptible strains of Staphylococcus aureus. Antimicrob Agents Chemother. 2010;54:773\u20137.","journal-title":"Antimicrob Agents Chemother"},{"key":"788_CR54","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.2165\/00003495-200262070-00005","volume":"62","author":"HM Lamb","year":"2002","unstructured":"Lamb HM, Ormrod D, Scott LJ, Figgitt DP. Ceftriaxone: an update of its use in the management of community-acquired and nosocomial infections. Drugs. 2002;62:1041\u201389.","journal-title":"Drugs"},{"key":"788_CR55","doi-asserted-by":"publisher","first-page":"913","DOI":"10.2165\/00003495-200464090-00001","volume":"64","author":"F Van Bambeke","year":"2004","unstructured":"Van Bambeke F, Van Laethem Y, Courvalin P, Tulkens PM. Glycopeptide antibiotics. Drugs. 2004;64:913\u201336.","journal-title":"Drugs"},{"key":"788_CR56","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/ja.2017.56","volume":"70","author":"F Tabuchi","year":"2017","unstructured":"Tabuchi F, Matsumoto Y, Ishii M, Tatsuno K, Okazaki M, Sato T, et al. D-cycloserine increases the effectiveness of vancomycin against vancomycin-highly resistant Staphylococcus aureus. J Antibiotics. 2017;70:907\u201310.","journal-title":"J Antibiotics"},{"key":"788_CR57","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41589-018-0041-4","volume":"14","author":"M Santiago","year":"2018","unstructured":"Santiago M, Lee W, Fayad AA, Coe KA, Rajagopal M, Do T, et al. Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic. Nat Chem Biol. 2018;14:601\u20138.","journal-title":"Nat Chem Biol"},{"key":"788_CR58","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41429-024-00739-x","volume":"77","author":"H Hamamoto","year":"2024","unstructured":"Hamamoto H. Silkworm model of bacterial infection facilitates the identification of lysocin E, a potent, ultra-rapid bactericidal antibiotic. J Antibiot (Tokyo). 2024;77:477\u201385.","journal-title":"J Antibiot (Tokyo)"}],"container-title":["The Journal of Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41429-024-00788-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41429-024-00788-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41429-024-00788-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T23:03:13Z","timestamp":1737932593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41429-024-00788-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,14]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["788"],"URL":"https:\/\/doi.org\/10.1038\/s41429-024-00788-2","relation":{},"ISSN":["0021-8820","1881-1469"],"issn-type":[{"value":"0021-8820","type":"print"},{"value":"1881-1469","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,14]]},"assertion":[{"value":"1 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}