{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:15:09Z","timestamp":1791321309981,"version":"4.3.1"},"reference-count":109,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI137273"],"award-info":[{"award-number":["R01AI137273"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["398967434 \u2013 TRR261"],"award-info":[{"award-number":["398967434 \u2013 TRR261"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000923","name":"Silicon Valley Community Foundation","doi-asserted-by":"publisher","award":["2020\u2013225716"],"award-info":[{"award-number":["2020\u2013225716"]}],"id":[{"id":"10.13039\/100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,3,5]]},"abstract":"<jats:p>\n                    Antibiotic tolerance and antibiotic resistance are the two major obstacles to the efficient and reliable treatment of bacterial infections. Identifying antibiotic adjuvants that sensitize resistant and tolerant bacteria to antibiotic killing may lead to the development of superior treatments with improved outcomes. Vancomycin, a lipid II inhibitor, is a frontline antibiotic for treating methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    and other Gram-positive bacterial infections. However, vancomycin use has led to the increasing prevalence of bacterial strains with reduced susceptibility to vancomycin. Here, we show that unsaturated fatty acids act as potent vancomycin adjuvants to rapidly kill a range of Gram-positive bacteria, including vancomycin-tolerant and resistant populations. The synergistic bactericidal activity relies on the accumulation of membrane-bound cell wall intermediates that generate large fluid patches in the membrane leading to protein delocalization, aberrant septal formation, and loss of membrane integrity. Our findings provide a natural therapeutic option that enhances vancomycin activity against difficult-to-treat pathogens, and the underlying mechanism may be further exploited to develop antimicrobials that target recalcitrant infection.\n                  <\/jats:p>","DOI":"10.7554\/elife.80246","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T08:00:40Z","timestamp":1678089640000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.80246","source":"Crossref","is-referenced-by-count":25,"title":["Antibiotic-induced accumulation of lipid II synergizes with antimicrobial fatty acids to eradicate bacterial populations"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8700-261X","authenticated-orcid":true,"given":"Ashelyn E","family":"Sidders","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill","place":["Chapel Hill, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna M","family":"Kedziora","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genetics, University of North Carolina at Chapel Hill","place":["Chapel Hill, United States"]},{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Bioinformatics and Analytics Research Collaborative, University of North Carolina at Chapel Hill","place":["Chapel Hill, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Arts","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/041nas322","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Pharmaceutical Microbiology, University of Bonn","place":["Bonn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Martin","family":"Daniel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/041nas322","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Pharmaceutical Microbiology, University of Bonn","place":["Bonn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"de Benedetti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/041nas322","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Pharmaceutical Microbiology, University of Bonn","place":["Bonn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna E","family":"Beam","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill","place":["Chapel Hill, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duyen T","family":"Bui","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill","place":["Chapel Hill, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua B","family":"Parsons","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill","place":["Chapel Hill, United States"]},{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Duke University","place":["Durham, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-4716","authenticated-orcid":true,"given":"Tanja","family":"Schneider","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/041nas322","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Pharmaceutical Microbiology, University of Bonn","place":["Bonn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-359X","authenticated-orcid":true,"given":"Sarah E","family":"Rowe","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill","place":["Chapel Hill, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2155-8375","authenticated-orcid":true,"given":"Brian P","family":"Conlon","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill","place":["Chapel Hill, United States"]},{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill","place":["Chapel Hill, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1038\/s41564-021-00966-0","article-title":"Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes","volume":"6","author":"Aggarwala","year":"2021","journal-title":"Nature Microbiology"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2010.00134","article-title":"A brief history of the antibiotic era: lessons learned and challenges for the future","volume":"1","author":"Aminov","year":"2010","journal-title":"Frontiers in Microbiology"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006701","article-title":"A genetic switch controls the production of flagella and toxins in Clostridium difficile","volume":"13","author":"Anjuwon-Foster","year":"2017","journal-title":"PLOS Genetics"},{"key":"bib4","volume-title":"Topical Antibiotics for Infection Prevention: A Review of the Clinical Effectiveness and Guidelines","author":"Banerjee","year":"2017"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02767-21","article-title":"Host polyunsaturated fatty acids potentiate aminoglycoside killing of Staphylococcus aureus","volume":"10","author":"Beavers","year":"2022","journal-title":"Microbiology Spectrum"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1128\/AAC.00603-08","article-title":"Ultrastructural effects of oritavancin on methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus","volume":"53","author":"Belley","year":"2009","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1021\/acsinfecdis.7b00258","article-title":"Developments in glycopeptide antibiotics","volume":"4","author":"Blaskovich","year":"2018","journal-title":"ACS Infectious Diseases"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1126\/science.277.5331.1453","article-title":"The complete genome sequence of Escherichia coli K-12","volume":"277","author":"Blattner","year":"1997","journal-title":"Science"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"e00023","DOI":"10.1128\/AAC.00023-18","article-title":"Impact of bacterial membrane fatty acid composition on the failure of daptomycin to kill Staphylococcus aureus","volume":"62","author":"Boudjemaa","year":"2018","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1017\/s0022172400035373","article-title":"The mechanism of self-disinfection of the human skin and its appendages","volume":"42","author":"Burtenshaw","year":"1942","journal-title":"The Journal of Hygiene"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1128\/AAC.01043-13","article-title":"Bactericidal activity of the human skin fatty acid cis-6-hexadecanoic acid on Staphylococcus aureus","volume":"58","author":"Cartron","year":"2014","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.1038\/srep01678","article-title":"Lipid-II forms potential \u201c landing terrain\u201d for lantibiotics in simulated bacterial membrane","volume":"3","author":"Chugunov","year":"2013","journal-title":"Scientific Reports"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1080\/1040841X.2018.1467875","article-title":"Alternative antimicrobials: the properties of fatty acids and monoglycerides","volume":"44","author":"Churchward","year":"2018","journal-title":"Critical Reviews in Microbiology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"4268","DOI":"10.1128\/JB.01946-14","article-title":"Role for the a domain of unprocessed accumulation-associated protein (Aap) in the attachment phase of the Staphylococcus epidermidis biofilm phenotype","volume":"196","author":"Conlon","year":"2014","journal-title":"Journal of Bacteriology"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.51","article-title":"Persister formation in Staphylococcus aureus is associated with ATP depletion","volume":"1","author":"Conlon","year":"2016","journal-title":"Nature Microbiology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"e00181","DOI":"10.1128\/CMR.00181-19","article-title":"Antimicrobial resistance in ESKAPE pathogens","volume":"33","author":"De Oliveira","year":"2020","journal-title":"Clinical Microbiology Reviews"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"4177","DOI":"10.4049\/jimmunol.181.6.4177","article-title":"Lipids including cholesteryl linoleate and cholesteryl arachidonate contribute to the inherent antibacterial activity of human nasal fluid","volume":"181","author":"Do","year":"2008","journal-title":"Journal of Immunology"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.bbamem.2015.10.018","article-title":"Molecular mechanisms of membrane targeting antibiotics","volume":"1858","author":"Epand","year":"2016","journal-title":"Biochimica et Biophysica Acta"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1128\/CMR.00068-15","article-title":"Fosfomycin","volume":"29","author":"Falagas","year":"2016","journal-title":"Clinical Microbiology Reviews"},{"key":"bib20","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00537-12","article-title":"A genetic resource for rapid and comprehensive phenotype screening of nonessential Staphylococcus aureus genes","volume":"4","author":"Fey","year":"2013","journal-title":"MBio"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9020075","article-title":"Antimicrobial activity of host-derived lipids","volume":"9","author":"Fischer","year":"2020","journal-title":"Antibiotics"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/j.cell.2017.10.012","article-title":"Membrane microdomain disassembly inhibits MRSA antibiotic resistance","volume":"171","author":"Garc\u00eda-Fern\u00e1ndez","year":"2017","journal-title":"Cell"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"4512","DOI":"10.1128\/IAI.73.8.4512-4521.2005","article-title":"A Toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with gram-positive bacteria","volume":"73","author":"Georgel","year":"2005","journal-title":"Infection and Immunity"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1021\/acsinfecdis.0c00001","article-title":"Multitarget approaches against multiresistant superbugs","volume":"6","author":"Gray","year":"2020","journal-title":"ACS Infectious Diseases"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9010017","article-title":"More than a pore: a current perspective on the in vivo mode of action of the lipopeptide antibiotic daptomycin","volume":"9","author":"Gray","year":"2020","journal-title":"Antibiotics"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"3520","DOI":"10.1016\/j.jmb.2019.05.014","article-title":"Docking on lipid II-A widespread mechanism for potent bactericidal activities of antibiotic peptides","volume":"431","author":"Grein","year":"2019","journal-title":"Journal of Molecular Biology"},{"key":"bib27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15257-1","article-title":"Ca2+-daptomycin targets cell wall biosynthesis by forming a tripartite complex with undecaprenyl-coupled intermediates and membrane lipids","volume":"11","author":"Grein","year":"2020","journal-title":"Nature Communications"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijmm.2016.12.001","article-title":"The cell wall precursor lipid II acts as a molecular signal for the Ser\/Thr kinase PknB of Staphylococcus aureus","volume":"307","author":"Hardt","year":"2017","journal-title":"International Journal of Medical Microbiology"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"2877","DOI":"10.1128\/IAI.00088-10","article-title":"Repair of global regulators in Staphylococcus aureus 8325 and comparative analysis with other clinical isolates","volume":"78","author":"Herbert","year":"2010","journal-title":"Infection and Immunity"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"6970","DOI":"10.1128\/AAC.03672-14","article-title":"Antibacterial synergy of glycerol monolaurate and aminoglycosides in Staphylococcus aureus biofilms","volume":"58","author":"Hess","year":"2014","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1016\/j.chom.2021.10.002","article-title":"The vulnerable versatility of salmonella antibiotic persisters during infection","volume":"29","author":"Hill","year":"2021","journal-title":"Cell Host & Microbe"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.3390\/info11020108","article-title":"Fastai: a layered API for deep learning","volume":"11","author":"Howard","year":"2020","journal-title":"Information"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/nrmicro2474","article-title":"Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections","volume":"9","author":"Hurdle","year":"2011","journal-title":"Nature Reviews. Microbiology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1128\/AAC.2.1.23","article-title":"Fatty acids and derivatives as antimicrobial agents","volume":"2","author":"Kabara","year":"1972","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1073\/pnas.0710217105","article-title":"Epidemic community-associated methicillin-resistant Staphylococcus aureus: recent clonal expansion and diversification","volume":"105","author":"Kennedy","year":"2008","journal-title":"PNAS"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/nature26157","article-title":"A new class of synthetic retinoid antibiotics effective against bacterial persisters","volume":"556","author":"Kim","year":"2018","journal-title":"Nature"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"16529","DOI":"10.1073\/pnas.1904700116","article-title":"A selective membrane-targeting repurposed antibiotic with activity against persistent methicillin-resistant Staphylococcus aureus","volume":"116","author":"Kim","year":"2019","journal-title":"PNAS"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1042\/bj0390078","article-title":"The effect of unsaturated fatty acids on Lactobacillus helveticus and other gram-positive micro-organisms","volume":"39","author":"Kodicek","year":"1945","journal-title":"The Biochemical Journal"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"S191","DOI":"10.1086\/519470","article-title":"Limitations of vancomycin in the management of resistant staphylococcal infections","volume":"45 Suppl 3","author":"Kollef","year":"2007","journal-title":"Clinical Infectious Diseases"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1093\/jac\/42.2.227","article-title":"Bacterial concentrations in pus and infected peritoneal fluid -- implications for bactericidal activity of antibiotics","volume":"42","author":"K\u00f6nig","year":"1998","journal-title":"The Journal of Antimicrobial Chemotherapy"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"4510","DOI":"10.1128\/AAC.01073-08","article-title":"Incidence and characteristics of vancomycin nonsusceptible strains of methicillin-resistant Staphylococcus aureus at hershey medical center","volume":"52","author":"Kosowska-Shick","year":"2008","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"4907","DOI":"10.1021\/ja100351w","article-title":"Switchable Nile red-based probe for cholesterol and lipid order at the outer leaflet of biomembranes","volume":"132","author":"Kucherak","year":"2010","journal-title":"Journal of the American Chemical Society"},{"key":"bib43","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00219-20","article-title":"Novel functions and signaling specificity for the GRAS sensor kinase of Staphylococcus aureus in response to acidic pH","volume":"202","author":"Kuiack","year":"2020","journal-title":"Journal of Bacteriology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nprot.2014.197","article-title":"Synthesis of fluorescent D-amino acids and their use for probing peptidoglycan synthesis and bacterial growth in situ","volume":"10","author":"Kuru","year":"2015","journal-title":"Nature Protocols"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1084\/jem.13.3.380","article-title":"CHEMO-IMMUNOLOGICAL studies on localized infections: second paper: lysis of the pneumococcus and hemolysis by certain fatty acids and their alkali soaps","volume":"13","author":"Lamar","year":"1911","journal-title":"The Journal of Experimental Medicine"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"4665","DOI":"10.1128\/AAC.48.12.4665-4672.2004","article-title":"Impact of high-inoculum Staphylococcus aureus on the activities of nafcillin, vancomycin, linezolid, and daptomycin, alone and in combination with gentamicin, in an in vitro pharmacodynamic model","volume":"48","author":"LaPlante","year":"2004","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"bib47","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad7364","article-title":"TarO-specific inhibitors of wall teichoic acid biosynthesis restore \u03b2-lactam efficacy against methicillin-resistant staphylococci","volume":"8","author":"Lee","year":"2016","journal-title":"Science Translational Medicine"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1126\/science.aaj2191","article-title":"Antibiotic tolerance facilitates the evolution of resistance","volume":"355","author":"Levin-Reisman","year":"2017","journal-title":"Science"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.cell.2020.02.056","article-title":"The science of antibiotic discovery","volume":"181","author":"Lewis","year":"2020","journal-title":"Cell"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/nature14098","article-title":"A new antibiotic kills pathogens without detectable resistance","volume":"517","author":"Ling","year":"2015","journal-title":"Nature"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1126\/science.aay3041","article-title":"Effect of tolerance on the evolution of antibiotic resistance under drug combinations","volume":"367","author":"Liu","year":"2020","journal-title":"Science"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2014364118","article-title":"Inoculum effect of antimicrobial peptides","volume":"118","author":"Loffredo","year":"2021","journal-title":"PNAS"},{"key":"bib53","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.32057","article-title":"Molecular coordination of Staphylococcus aureus cell division","volume":"7","author":"Lund","year":"2018","journal-title":"eLife"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"2762","DOI":"10.1128\/IAI.00425-15","article-title":"Enterococcus faecalis gelatinase mediates intestinal permeability via protease-activated receptor 2","volume":"83","author":"Maharshak","year":"2015","journal-title":"Infection and Immunity"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"3743","DOI":"10.1128\/AAC.48.10.3743-3748.2004","article-title":"Acquired bacitracin resistance in Enterococcus faecalis is mediated by an ABC transporter and a novel regulatory protein, BcrR","volume":"48","author":"Manson","year":"2004","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1016\/j.cell.2020.05.005","article-title":"A dual-mechanism antibiotic kills gram-negative bacteria and avoids drug resistance","volume":"181","author":"Martin","year":"2020","journal-title":"Cell"},{"key":"bib57","first-page":"269","article-title":"Vancomycin resistance in Staphylococcus aureus","volume":"90","author":"McGuinness","year":"2017","journal-title":"Yale J Biol Med"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1128\/iai.17.2.303-312.1977","article-title":"Inhibitory action of fatty acids on the growth of neisseria gonorrhoeae","volume":"17","author":"Miller","year":"1977","journal-title":"Infection and Immunity"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1039\/C5MD00503E","article-title":"Bacterial lipid membranes as promising targets to fight antimicrobial resistance, molecular foundations and illustration through the renewal of aminoglycoside antibiotics and emergence of amphiphilic aminoglycosides","volume":"7","author":"Mingeot-Leclercq","year":"2016","journal-title":"MedChemComm"},{"key":"bib60","doi-asserted-by":"publisher","DOI":"10.1038\/srep29707","article-title":"Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus","volume":"6","author":"Mohamed","year":"2016","journal-title":"Scientific Reports"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9055","article-title":"Cell shape dynamics during the staphylococcal cell cycle","volume":"6","author":"Monteiro","year":"2015","journal-title":"Nature Communications"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nature25506","article-title":"Peptidoglycan synthesis drives an ftsz-treadmilling-independent step of cytokinesis","volume":"554","author":"Monteiro","year":"2018","journal-title":"Nature"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"20270","DOI":"10.1074\/jbc.M112.369561","article-title":"Lipodepsipeptide empedopeptin inhibits cell wall biosynthesis through Ca2+-dependent complex formation with peptidoglycan precursors","volume":"287","author":"M\u00fcller","year":"2012","journal-title":"The Journal of Biological Chemistry"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"E7077","DOI":"10.1073\/pnas.1611173113","article-title":"Daptomycin inhibits cell envelope synthesis by interfering with fluid membrane microdomains","volume":"113","author":"M\u00fcller","year":"2016","journal-title":"PNAS"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1039\/c7np00012j","article-title":"Targeting a cell wall biosynthesis hot spot","volume":"34","author":"M\u00fcller","year":"2017","journal-title":"Natural Product Reports"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s00203-014-1048-1","article-title":"The effect of skin fatty acids on Staphylococcus aureus","volume":"197","author":"Neumann","year":"2015","journal-title":"Archives of Microbiology"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"5294","DOI":"10.1128\/JB.00743-12","article-title":"Membrane disruption by antimicrobial fatty acids releases low-molecular-weight proteins from Staphylococcus aureus","volume":"194","author":"Parsons","year":"2012","journal-title":"Journal of Bacteriology"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.2217\/fmb-2018-0216","article-title":"Is synergy the key to treating high-density infections?","volume":"13","author":"Pletzer","year":"2018","journal-title":"Future Microbiology"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/nchembio.2388","article-title":"Lipid II overproduction allows direct assay of transpeptidase inhibition by \u03b2-lactams","volume":"13","author":"Qiao","year":"2017","journal-title":"Nature Chemical Biology"},{"key":"bib70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2003981","article-title":"Pseudomonas aeruginosa exoproducts determine antibiotic efficacy against Staphylococcus aureus","volume":"15","author":"Radlinski","year":"2017","journal-title":"PLOS Biology"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1016\/j.chembiol.2019.07.009","article-title":"Chemical induction of aminoglycoside uptake overcomes antibiotic tolerance and resistance in Staphylococcus aureus","volume":"26","author":"Radlinski","year":"2019","journal-title":"Cell Chemical Biology"},{"key":"bib72","first-page":"1","volume-title":"In: Protein and Sugar Export and Assembly in Gram-Positive Bacteria","author":"Rajagopal","year":"2017"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1038\/s41564-019-0437-2","article-title":"SEDS-bpbp pairs direct lateral and septal peptidoglycan synthesis in Staphylococcus aureus","volume":"4","author":"Reichmann","year":"2019","journal-title":"Nature Microbiology"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1083\/jcb.17.1.208","article-title":"The use of lead citrate at high ph as an electron-opaque stain in electron microscopy","volume":"17","author":"Reynolds","year":"1963","journal-title":"The Journal of Cell Biology"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1093\/glycob\/8.6.557","article-title":"Characterization of the lipid-carrier involved in the synthesis of enterobacterial common antigen (ECA) and identification of a novel phosphoglyceride in a mutant of Salmonella typhimurium defective in ECA synthesis","volume":"8","author":"Rick","year":"1998","journal-title":"Glycobiology"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"2421","DOI":"10.1128\/aem.63.6.2421-2431.1997","article-title":"Bacterial viability and antibiotic susceptibility testing with sytox green nucleic acid stain","volume":"63","author":"Roth","year":"1997","journal-title":"Applied and Environmental Microbiology"},{"key":"bib77","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2014.00217","article-title":"Vancomycin revisited-60 years later","volume":"2","author":"Rubinstein","year":"2014","journal-title":"Frontiers in Public Health"},{"key":"bib78","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006876","article-title":"The novel antibiotic rhodomyrtone traps membrane proteins in vesicles with increased fluidity","volume":"14","author":"Saeloh","year":"2018","journal-title":"PLOS Pathogens"},{"key":"bib79","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17940-9","article-title":"Reassessment of the distinctive geometry of Staphylococcus aureus cell division","volume":"11","author":"Saraiva","year":"2020","journal-title":"Nature Communications"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nature Methods"},{"key":"bib81","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc09c03s32","article-title":"Genetic manipulation of Staphylococcus aureus","volume":"32","author":"Schneewind","year":"2014","journal-title":"Current Protocols in Microbiology"},{"key":"bib82","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1111\/j.1365-2958.2004.04149.x","article-title":"In vitro assembly of a complete, pentaglycine interpeptide bridge containing cell wall precursor (lipid II-gly5) of Staphylococcus aureus","volume":"53","author":"Schneider","year":"2004","journal-title":"Molecular Microbiology"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.ijmm.2009.10.005","article-title":"An oldie but a goodie-cell wall biosynthesis as antibiotic target pathway","volume":"300","author":"Schneider","year":"2010","journal-title":"International Journal of Medical Microbiology"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1038\/s41429-018-0090-7","article-title":"Evaluation of LL-37 antimicrobial peptide derivatives alone and in combination with vancomycin against S. aureus","volume":"71","author":"Shurko","year":"2018","journal-title":"The Journal of Antibiotics"},{"key":"bib85","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-1-0716-1621-5_15","volume-title":"In: Bacterial Persistence: Methods and Protocols","author":"Sidders","year":"2021"},{"key":"bib86","article-title":"Analysis of bacteria treated with antimicrobial fatty acids","volume-title":"Software Heritage","author":"Sidders","year":"2023","unstructured":"Sidders AE, Kedziora KM, Arts M, Daniel JM, de Benedetti S, Beam JE, Bui DT, Parsons J, Schneider T, Rowe SE, Conlon BP. 2023. Analysis of bacteria treated with antimicrobial fatty acids. Software Heritage. swh:1:rev:b18160031e6dd86bcd14d0dfb144c2ebd09c03b0. https:\/\/archive.softwareheritage.org\/swh:1:dir:809754cd5a7c5ace0644a2333acb44b6d1ccfe5a;origin=https:\/\/github.com\/fjorka\/bacteria_pa_van_analysis;visit=swh:1:snp:3a384e53243b3929f175e483cf5fe68fc5589444;anchor=swh:1:rev:b18160031e6dd86bcd14d0dfb144c2ebd09c03b0."},{"key":"bib87","doi-asserted-by":"publisher","first-page":"3925","DOI":"10.1021\/acs.jpcb.7b00324","article-title":"Hidden mode of action of glycopeptide antibiotics: inhibition of wall teichoic acid biosynthesis","volume":"121","author":"Singh","year":"2017","journal-title":"The Journal of Physical Chemistry. B"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1038\/nprot.2013.066","article-title":"Measuring mRNA copy number in individual Escherichia coli cells using single-molecule fluorescent in situ hybridization","volume":"8","author":"Skinner","year":"2013","journal-title":"Nature Protocols"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1038\/s41564-020-0723-z","article-title":"A broad-spectrum antibiotic adjuvant reverses multidrug-resistant gram-negative pathogens","volume":"5","author":"Song","year":"2020","journal-title":"Nature Microbiology"},{"key":"bib90","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1111\/j.1365-2958.2011.07591.x","article-title":"Multiple essential roles for EzrA in cell division of Staphylococcus aureus","volume":"80","author":"Steele","year":"2011","journal-title":"Molecular Microbiology"},{"key":"bib91","doi-asserted-by":"publisher","first-page":"3223","DOI":"10.1073\/pnas.68.12.3223","article-title":"Mechanism of action of bacitracin: complexation with metal ion and C 55 -isoprenyl pyrophosphate","volume":"68","author":"Stone","year":"1971","journal-title":"PNAS"},{"key":"bib92","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4442","article-title":"The actin homologue mreb organizes the bacterial cell membrane","volume":"5","author":"Strahl","year":"2014","journal-title":"Nature Communications"},{"key":"bib93","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s41592-020-01018-x","article-title":"Cellpose: a generalist algorithm for cellular segmentation","volume":"18","author":"Stringer","year":"2021","journal-title":"Nature Methods"},{"key":"bib94","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1159\/000087018","article-title":"Deficient production of hexadecenoic acid in the skin is associated in part with the vulnerability of atopic dermatitis patients to colonization by Staphylococcus aureus","volume":"211","author":"Takigawa","year":"2005","journal-title":"Dermatology"},{"key":"bib95","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/978-1-4939-8935-5","article-title":"Sample preparation for transmission electron microscopy","author":"Tizro","year":"1897","journal-title":"Methods in Molecular Biology"},{"key":"bib96","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1093\/jac\/dkn554","article-title":"Functional relationship between bacterial cell density and the efficacy of antibiotics","volume":"63","author":"Udekwu","year":"2009","journal-title":"The Journal of Antimicrobial Chemotherapy"},{"key":"bib97","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/s0140-6736(88)91037-9","article-title":"Vancomycin-resistant enterococci","volume":"1","author":"Uttley","year":"1988","journal-title":"Lancet"},{"key":"bib98","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1093\/femsre\/fux001","article-title":"Formation, physiology, ecology, evolution and clinical importance of bacterial persisters","volume":"41","author":"Van den Bergh","year":"2017","journal-title":"FEMS Microbiology Reviews"},{"key":"bib99","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.453","article-title":"Scikit-image: image processing in python","volume":"2","author":"van der Walt","year":"2014","journal-title":"PeerJ"},{"key":"bib100","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1128\/aem.58.2.624-629.1992","article-title":"Inhibition of listeria monocytogenes by fatty acids and monoglycerides","volume":"58","author":"Wang","year":"1992","journal-title":"Applied and Environmental Microbiology"},{"key":"bib101","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0205338","article-title":"Topical anti-inflammatory activity of palmitoleic acid improves wound healing","volume":"13","author":"Weimann","year":"2018","journal-title":"PLOS ONE"},{"key":"bib102","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3063","article-title":"Assessing membrane fluidity and visualizing fluid membrane domains in bacteria using fluorescent membrane dyes","volume":"8","author":"Wenzel","year":"2018","journal-title":"Bio-Protocol"},{"key":"bib103","doi-asserted-by":"publisher","first-page":"3259","DOI":"10.1128\/JB.186.10.3259-3261.2004","article-title":"Lipid II-mediated pore formation by the peptide antibiotic nisin: a black lipid membrane study","volume":"186","author":"Wiedemann","year":"2004","journal-title":"Journal of Bacteriology"},{"key":"bib104","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1159\/000069757","article-title":"Palmitoleic acid isomer (C16:1delta6) in human skin sebum is effective against gram-positive bacteria","volume":"16","author":"Wille","year":"2003","journal-title":"Skin Pharmacology and Applied Skin Physiology"},{"key":"bib105","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0215703","article-title":"SMode of action of the antimicrobial peptide mel4 is independent of staphyloc occus aureus cell mem brane permeability","volume":"14","author":"Yasir","year":"2019","journal-title":"PLOS ONE"},{"key":"bib106","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/j.1574-6968.2011.02291.x","article-title":"Bacitracin sensing and resistance in Staphylococcus aureus","volume":"320","author":"Yoshida","year":"2011","journal-title":"FEMS Microbiology Letters"},{"key":"bib107","doi-asserted-by":"publisher","first-page":"5157","DOI":"10.1016\/j.febslet.2005.08.028","article-title":"Fatty acid synthesis is a target for antibacterial activity of unsaturated fatty acids","volume":"579","author":"Zheng","year":"2005","journal-title":"FEBS Letters"},{"key":"bib108","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1126\/science.aaa1511","article-title":"Mechanical crack propagation drives millisecond daughter cell separation in staphylococcus aureus","volume":"348","author":"Zhou","year":"2015","journal-title":"Science"},{"key":"bib109","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57179","article-title":"Flotillin-mediated membrane fluidity controls peptidoglycan synthesis and mreb movement","volume":"9","author":"Zieli\u0144ska","year":"2020","journal-title":"eLife"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/80246\/elife-80246-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/80246\/elife-80246-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/80246","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:05:24Z","timestamp":1697058324000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/80246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,6]]},"references-count":109,"alternative-id":["10.7554\/eLife.80246"],"URL":"https:\/\/doi.org\/10.7554\/elife.80246","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.05.03.490474","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2022.05.03.490474","asserted-by":"object"}],"is-supplemented-by":[{"id-type":"doi","id":"10.5281\/zenodo.7753640","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.80246.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.80246.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.80246.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,6]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e80246"}}