{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:46:28Z","timestamp":1790952388634,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T00:00:00Z","timestamp":1590451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2020,6,30]]},"abstract":"<jats:p>\n                    Antimicrobial resistance is one of the greatest threats to the global health system. It is imperative that new anti-infective therapeutics be developed against problematic \u201csuperbugs.\u201d The cyclic depsipeptide teixobactin holds much promise as a new class of antibiotics for highly resistant Gram-positive pathogens (e.g., methicillin-resistant\n                    <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n                    [MRSA]). Understanding its molecular mechanism(s) of action could lead to the design of new compounds with a broader activity spectrum. Here, we describe the first metabolomics study to investigate the killing mechanism(s) of teixobactin against MRSA. Our findings revealed that teixobactin significantly disorganized the bacterial cell envelope, as reflected by a profound perturbation in the bacterial membrane lipids and cell wall biosynthesis (peptidoglycan and teichoic acid). Importantly, teixobactin significantly suppressed the main intermediate\n                    <jats:sc>d<\/jats:sc>\n                    -alanyl-\n                    <jats:sc>d<\/jats:sc>\n                    -lactate involved in the mechanism of vancomycin resistance in\n                    <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n                    . These novel results help explain the unique mechanism of action of teixobactin and its lack of cross-resistance with vancomycin.\n                  <\/jats:p>","DOI":"10.1128\/msystems.00077-20","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T09:15:47Z","timestamp":1590398147000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["The Killing Mechanism of Teixobactin against Methicillin-Resistant Staphylococcus aureus: an Untargeted Metabolomics Study"],"prefix":"10.1128","volume":"5","author":[{"given":"Maytham","family":"Hussein","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Karas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena K.","family":"Schneider-Futschik","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Swarbrick","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia K. A.","family":"Paulin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hoyer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia"},{"name":"The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia"},{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Baker","sequence":"additional","affiliation":[{"name":"Discipline of Biological Sciences, Priority Research Centre in Reproductive Biology, Faculty of Science and IT, University of Newcastle, Callaghan, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7342-3782","authenticated-orcid":false,"given":"Yan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Velkov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Antimicrobial resistance: global report on surveillance 2014","author":"WHO","year":"2014","unstructured":"WHO. 2014. Antimicrobial resistance: global report on surveillance 2014. WHO, Geneva, Switzerland."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/499819"},{"key":"e_1_3_2_4_2","volume-title":"Drug-resistant infections: a threat to our economic future","author":"Jonas OB","year":"2017","unstructured":"Jonas OB, Irwin A, Berthe FCJ, Le Gall FG, Marquez PV. 2017. Drug-resistant infections: a threat to our economic future. HNP\/Agriculture Global Antimicrobial Resistance Initiative, Washington, DC."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3975"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14098"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.7b00108"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.6b01324"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2017.09.040"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14282"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201704167"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201501440"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2008.09.020"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2013.100"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.16.4.673-687.2003"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201601315"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2015.10.024"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2004"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904686106"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01050-16"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12394"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01241"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2018.01.016"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1039\/c6cc09490b"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/psc.3206"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-092412-155620"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.3.6.1.9"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00020-06"},{"key":"e_1_3_2_29_2","first-page":"3","article-title":"Evolutionary roots of the citric acid cycle in prokaryotes","volume":"54","author":"Gest H","year":"1987","unstructured":"Gest H. 1987. Evolutionary roots of the citric acid cycle in prokaryotes. Biochem Soc Symp 54:3\u201316.","journal-title":"Biochem Soc Symp"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17030363"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.3.6.3.4"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts069"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac2000994"},{"key":"e_1_3_2_34_2","volume-title":"Metabolomics: practical guide to design and analysis","author":"Wehrens R","year":"2020","unstructured":"Wehrens R, Salek RM (ed). 2020. Metabolomics: practical guide to design and analysis. CRC Press, Boca Raton, FL."}],"container-title":["mSystems"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msystems.00077-20","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msystems.00077-20","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,11]],"date-time":"2024-08-11T14:57:12Z","timestamp":1723388232000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/msystems.00077-20"}},"subtitle":[],"editor":[{"given":"Karen G.","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,6,30]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,6,30]]}},"alternative-id":["10.1128\/msystems.00077-20"],"URL":"https:\/\/doi.org\/10.1128\/msystems.00077-20","relation":{},"ISSN":["2379-5077"],"issn-type":[{"value":"2379-5077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,30]]},"assertion":[{"value":"2020-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"10.1128\/msystems.00077-20"}}