{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T19:54:33Z","timestamp":1773258873071,"version":"3.50.1"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"publisher","award":["2015-68004-23131"],"award-info":[{"award-number":["2015-68004-23131"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Avian pathogenic <jats:italic>Escherichia coli<\/jats:italic> (APEC), a most common bacterial pathogen of poultry, causes multiple extra-intestinal diseases in poultry which results in significant economic losses to the poultry industry worldwide. In addition, APEC are a subgroup of extra-intestinal pathogenic <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> (ExPEC), and APEC contaminated poultry products are a potential source of foodborne ExPEC infections to humans and transfer of antimicrobial resistant genes. The emergence of multi-drug resistant APEC strains and the limited efficacy of vaccines necessitate novel APEC control approaches. Here, we screened a small molecule (SM) library and identified 11 SMs bactericidal to APEC. The identified SMs were effective against multiple APEC serotypes, biofilm embedded APEC, antimicrobials resistant APECs, and other pathogenic <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> strains. Microscopy revealed that these SMs affect the APEC cell membrane. Exposure of SMs to APEC revealed no resistance. Most SMs showed low toxicity towards chicken and human cells and reduced the intracellular APEC load. Treatment with most SMs extended the wax moth larval survival and reduced the intra-larval APEC load. Our studies could facilitate the development of antimicrobial therapeutics for the effective management of APEC infections in poultry as well as other <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> related foodborne zoonosis, including APEC related ExPEC infections in humans.<\/jats:p>","DOI":"10.1038\/s41598-018-33587-5","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T15:27:57Z","timestamp":1539271677000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Novel small molecules affecting cell membrane as potential therapeutics for avian pathogenic Escherichia coli"],"prefix":"10.1038","volume":"8","author":[{"given":"Dipak","family":"Kathayat","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosra A.","family":"Helmy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loic","family":"Deblais","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gireesh","family":"Rajashekara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"33587_CR1","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1089\/fpd.2013.1533","volume":"10","author":"M Mellata","year":"2013","unstructured":"Mellata, M. Human and Avian Extraintestinal Pathogenic Escherichia coli: Infections, Zoonotic Risks, and Antibiotic Resistance Trends. Foodborne Pathogens and Disease 10, 916\u2013932, https:\/\/doi.org\/10.1089\/fpd.2013.1533 (2013).","journal-title":"Foodborne Pathogens and Disease"},{"key":"33587_CR2","doi-asserted-by":"publisher","unstructured":"Huja, S. et al. Genomic Avenue to Avian Colisepticemia. mBio 6, https:\/\/doi.org\/10.1128\/mBio.01681-14 (2015).","DOI":"10.1128\/mBio.01681-14"},{"key":"33587_CR3","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.ijmm.2007.01.003","volume":"297","author":"C Ewers","year":"2007","unstructured":"Ewers, C. et al. Avian pathogenic, uropathogenic, and newborn meningitis-causing Escherichia coli: How closely related are they? International Journal of Medical Microbiology 297, 163\u2013176, https:\/\/doi.org\/10.1016\/j.ijmm.2007.01.003 (2007).","journal-title":"International Journal of Medical Microbiology"},{"key":"33587_CR4","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1586\/eri.12.110","volume":"10","author":"JDD Pitout","year":"2012","unstructured":"Pitout, J. D. D. Extraintestinal pathogenic Escherichia coli: an update on antimicrobial resistance, laboratory diagnosis and treatment. Expert Review of Anti-infective Therapy 10, 1165\u20131176, https:\/\/doi.org\/10.1586\/eri.12.110 (2012).","journal-title":"Expert Review of Anti-infective Therapy"},{"key":"33587_CR5","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1017\/s1466252308001552","volume":"9","author":"CL Gyles","year":"2008","unstructured":"Gyles, C. L. Antimicrobial resistance in selected bacteria from poultry. Animal health research reviews 9, 149\u2013158, https:\/\/doi.org\/10.1017\/s1466252308001552 (2008).","journal-title":"Animal health research reviews"},{"key":"33587_CR6","doi-asserted-by":"publisher","first-page":"601","DOI":"10.3382\/ps\/pev008","volume":"94","author":"Y Li","year":"2015","unstructured":"Li, Y., Chen, L., Wu, X. & Huo, S. Molecular characterization of multidrug-resistant avian pathogenic Escherichia coli isolated from septicemic broilers. Poultry science 94, 601\u2013611, https:\/\/doi.org\/10.3382\/ps\/pev008 (2015).","journal-title":"Poultry science"},{"key":"33587_CR7","doi-asserted-by":"publisher","unstructured":"Cunha, M. P. V. et al. Coexistence of CTX-M-2, CTX-M-55, CMY-2, FosA3 and QnrB19 in Extraintestinal Pathogenic Escherichia coli from Poultry in Brazil. Antimicrobial Agents and Chemotherapy, https:\/\/doi.org\/10.1128\/aac.02474-16 (2017).","DOI":"10.1128\/aac.02474-16"},{"key":"33587_CR8","doi-asserted-by":"publisher","first-page":"4414","DOI":"10.1128\/aac.00548-16","volume":"60","author":"V Perreten","year":"2016","unstructured":"Perreten, V., Strauss, C., Collaud, A. & Gerber, D. Colistin Resistance Gene mcr-1 in Avian-Pathogenic Escherichia coli in South Africa. Antimicrobial Agents and Chemotherapy 60, 4414\u20134415, https:\/\/doi.org\/10.1128\/aac.00548-16 (2016).","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"33587_CR9","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.vetmic.2014.04.019","volume":"172","author":"H Ghunaim","year":"2014","unstructured":"Ghunaim, H., Abu-Madi, M. A. & Kariyawasam, S. Advances in vaccination against avian pathogenic Escherichia coli respiratory disease: potentials and limitations. Veterinary microbiology 172, 13\u201322, https:\/\/doi.org\/10.1016\/j.vetmic.2014.04.019 (2014).","journal-title":"Veterinary microbiology"},{"key":"33587_CR10","volume-title":"Drug Discovery","author":"Elizabeth Hong-Geller","year":"2013","unstructured":"Hong-Geller, E. & Micheva-Viteva, S. Small Molecule Screens to Identify Inhibitors of Infectious Disease. (2013)."},{"key":"33587_CR11","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/sj.bjp.0706873","volume":"149","author":"R De La Fuente","year":"2006","unstructured":"De La Fuente, R., Sonawane, N. D., Arumainayagam, D. & Verkman, A. S. Small molecules with antimicrobial activity against E. coli and P. aeruginosa identified by high-throughput screening. British Journal of Pharmacology 149, 551\u2013559, https:\/\/doi.org\/10.1038\/sj.bjp.0706873 (2006).","journal-title":"British Journal of Pharmacology"},{"key":"33587_CR12","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1021\/cb300151m","volume":"7","author":"SA Stanley","year":"2012","unstructured":"Stanley, S. A. et al. Identification of novel inhibitors of M. tuberculosis growth using whole cell based high-throughput screening. ACS chemical biology 7, 1377\u20131384, https:\/\/doi.org\/10.1021\/cb300151m (2012).","journal-title":"ACS chemical biology"},{"key":"33587_CR13","doi-asserted-by":"publisher","first-page":"405","DOI":"10.3389\/fmicb.2016.00405","volume":"7","author":"A Kumar","year":"2016","unstructured":"Kumar, A. et al. Novel Anti-Campylobacter Compounds Identified Using High Throughput Screening of a Pre-selected Enriched Small Molecules Library. Frontiers in microbiology 7, 405, https:\/\/doi.org\/10.3389\/fmicb.2016.00405 (2016).","journal-title":"Frontiers in microbiology"},{"key":"33587_CR14","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.3389\/fmicb.2015.01127","volume":"6","author":"X Xu","year":"2015","unstructured":"Xu, X. et al. Discovery of novel small molecule modulators of Clavibacter michiganensis subsp. michiganensis. Front Microbiol 6, 1127, https:\/\/doi.org\/10.3389\/fmicb.2015.01127 (2015).","journal-title":"Front Microbiol"},{"key":"33587_CR15","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1016\/j.chembiol.2011.07.018","volume":"18","author":"IM Wallace","year":"2011","unstructured":"Wallace, I. M. et al. Compound prioritization methods increase rates of chemical probe discovery in model organisms. Chemistry & biology 18, 1273\u20131283, https:\/\/doi.org\/10.1016\/j.chembiol.2011.07.018 (2011).","journal-title":"Chemistry & biology"},{"key":"33587_CR16","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1111\/j.1365-2672.2006.03076.x","volume":"102","author":"JA Skyberg","year":"2007","unstructured":"Skyberg, J. A., Siek, K. E., Doetkott, C. & Nolan, L. K. Biofilm formation by avian Escherichia coli in relation to media, source and phylogeny. Journal of Applied Microbiology 102, 548\u2013554, https:\/\/doi.org\/10.1111\/j.1365-2672.2006.03076.x (2007).","journal-title":"Journal of Applied Microbiology"},{"key":"33587_CR17","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/nchembio.1361","volume":"9","author":"S Zlitni","year":"2013","unstructured":"Zlitni, S., Ferruccio, L. F. & Brown, E. D. Metabolic suppression identifies new antibacterial inhibitors under nutrient limitation. Nature chemical biology 9, 796\u2013804, https:\/\/doi.org\/10.1038\/nchembio.1361 (2013).","journal-title":"Nature chemical biology"},{"key":"33587_CR18","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1177\/108705719900400206","volume":"4","author":"JH Zhang","year":"1999","unstructured":"Zhang, J. H., Chung, T. D. & Oldenburg, K. R. A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. Journal of biomolecular screening 4, 67\u201373, https:\/\/doi.org\/10.1177\/108705719900400206 (1999).","journal-title":"Journal of biomolecular screening"},{"issue":"7535","key":"33587_CR19","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/nature14098","volume":"517","author":"Losee L. Ling","year":"2015","unstructured":"Ling, L. L. et al. A new antibiotic kills pathogens without detectable resistance. Nature 517, 455\u2013459, https:\/\/doi.org\/10.1038\/nature14098 http:\/\/www.nature.com\/nature\/journal\/v517\/n7535\/abs\/nature14098.html#supplementary-information (2015).","journal-title":"Nature"},{"key":"33587_CR20","unstructured":"CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 27th ed. CLSI supplement M100 (2017)."},{"key":"33587_CR21","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.vetmic.2005.01.021","volume":"107","author":"S Zhao","year":"2005","unstructured":"Zhao, S. et al. Antimicrobial susceptibility and molecular characterization of avian pathogenic Escherichia coli isolates. Veterinary microbiology 107, 215\u2013224, https:\/\/doi.org\/10.1016\/j.vetmic.2005.01.021 (2005).","journal-title":"Veterinary microbiology"},{"key":"33587_CR22","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1128\/JCM.37.6.1771-1776.1999","volume":"37","author":"H Ceri","year":"1999","unstructured":"Ceri, H. et al. The Calgary Biofilm Device: New Technology for Rapid Determination of Antibiotic Susceptibilities of Bacterial Biofilms. Journal of Clinical Microbiology 37, 1771\u20131776 (1999).","journal-title":"Journal of Clinical Microbiology"},{"key":"33587_CR23","doi-asserted-by":"publisher","first-page":"3353","DOI":"10.1128\/jcm.00494-10","volume":"48","author":"K Amsler","year":"2010","unstructured":"Amsler, K., Santoro, C., Foleno, B., Bush, K. & Flamm, R. Comparison of broth microdilution, agar dilution, and Etest for susceptibility testing of doripenem against gram-negative and gram-positive pathogens. J Clin Microbiol 48, 3353\u20133357, https:\/\/doi.org\/10.1128\/jcm.00494-10 (2010).","journal-title":"J Clin Microbiol"},{"key":"33587_CR24","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jgar.2016.07.007","volume":"7","author":"G Igawa","year":"2016","unstructured":"Igawa, G. et al. Comparison of agar dilution and broth microdilution methods for Clostridium difficile antimicrobial susceptibility testing. Journal of global antimicrobial resistance 7, 43\u201345, https:\/\/doi.org\/10.1016\/j.jgar.2016.07.007 (2016).","journal-title":"Journal of global antimicrobial resistance"},{"key":"33587_CR25","doi-asserted-by":"publisher","first-page":"16169","DOI":"10.1073\/pnas.1311066110","volume":"110","author":"P Nonejuie","year":"2013","unstructured":"Nonejuie, P., Burkart, M., Pogliano, K. & Pogliano, J. Bacterial cytological profiling rapidly identifies the cellular pathways targeted by antibacterial molecules. Proceedings of the National Academy of Sciences of the United States of America 110, 16169\u201316174, https:\/\/doi.org\/10.1073\/pnas.1311066110 (2013).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"33587_CR26","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1186\/1471-2180-12-258","volume":"12","author":"II Kassem","year":"2012","unstructured":"Kassem, I. I. et al. Respiratory proteins contribute differentially to Campylobacter jejuni\u2019s survival and in vitro interaction with hosts\u2019 intestinal cells. BMC Microbiology 12, 258\u2013258, https:\/\/doi.org\/10.1186\/1471-2180-12-258 (2012).","journal-title":"BMC Microbiology"},{"key":"33587_CR27","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.jep.2010.04.025","volume":"130","author":"KP Devi","year":"2010","unstructured":"Devi, K. P., Nisha, S. A., Sakthivel, R. & Pandian, S. K. Eugenol (an essential oil of clove) acts as an antibacterial agent against Salmonella typhi by disrupting the cellular membrane. Journal of ethnopharmacology 130, 107\u2013115, https:\/\/doi.org\/10.1016\/j.jep.2010.04.025 (2010).","journal-title":"Journal of ethnopharmacology"},{"key":"33587_CR28","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1128\/iai.03003-14","volume":"83","author":"RJ Cieza","year":"2015","unstructured":"Cieza, R. J., Hu, J., Ross, B. N., Sbrana, E. & Torres, A. G. The IbeA invasin of adherent-invasive Escherichia coli mediates interaction with intestinal epithelia and macrophages. Infection and immunity 83, 1904\u20131918, https:\/\/doi.org\/10.1128\/iai.03003-14 (2015).","journal-title":"Infection and immunity"},{"key":"33587_CR29","doi-asserted-by":"publisher","first-page":"2474","DOI":"10.1128\/jb.02074-12","volume":"195","author":"Q Gao","year":"2013","unstructured":"Gao, Q. et al. RfaH promotes the ability of the avian pathogenic Escherichia coli O2 strain E058 to cause avian colibacillosis. Journal of bacteriology 195, 2474\u20132480, https:\/\/doi.org\/10.1128\/jb.02074-12 (2013).","journal-title":"Journal of bacteriology"},{"key":"33587_CR30","doi-asserted-by":"publisher","first-page":"3843","DOI":"10.1128\/JB.182.13.3843-3845.2000","volume":"182","author":"G Jander","year":"2000","unstructured":"Jander, G., Rahme, L. G. & Ausubel, F. M. Positive Correlation between Virulence of Pseudomonas aeruginosa Mutants in Mice and Insects. Journal of bacteriology 182, 3843\u20133845 (2000).","journal-title":"Journal of bacteriology"},{"key":"33587_CR31","doi-asserted-by":"publisher","first-page":"3635609","DOI":"10.1155\/2017\/3635609","volume":"2017","author":"SK Garg","year":"2017","unstructured":"Garg, S. K. et al. Resurgence of Polymyxin B for MDR\/XDR Gram-Negative Infections: An Overview of Current Evidence. Critical Care Research and Practice 2017, 3635609, https:\/\/doi.org\/10.1155\/2017\/3635609 (2017).","journal-title":"Critical Care Research and Practice"},{"key":"33587_CR32","doi-asserted-by":"publisher","first-page":"2838","DOI":"10.1128\/aac.45.10.2838-2844.2001","volume":"45","author":"L Saiman","year":"2001","unstructured":"Saiman, L. et al. Cathelicidin Peptides Inhibit Multiply Antibiotic-Resistant Pathogens from Patients with Cystic Fibrosis. Antimicrobial Agents and Chemotherapy 45, 2838\u20132844, https:\/\/doi.org\/10.1128\/aac.45.10.2838-2844.2001 (2001).","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"33587_CR33","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ijheh.2016.10.011","volume":"220","author":"E Kintz","year":"2017","unstructured":"Kintz, E., Brainard, J., Hooper, L. & Hunter, P. Transmission pathways for sporadic Shiga-toxin producing E. coli infections: A systematic review and meta-analysis. International Journal of Hygiene and Environmental Health 220, 57\u201367, https:\/\/doi.org\/10.1016\/j.ijheh.2016.10.011 (2017).","journal-title":"International Journal of Hygiene and Environmental Health"},{"issue":"11","key":"33587_CR34","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1136\/gutjnl-2012-303184","volume":"62","author":"Ana Elena P\u00e9rez-Cobas","year":"2012","unstructured":"Perez-Cobas, A. E. et al. Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut 62, https:\/\/doi.org\/10.1136\/gutjnl-2012-303184 (2013).","journal-title":"Gut"},{"key":"33587_CR35","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.3389\/fmicb.2015.01543","volume":"6","author":"MP Francino","year":"2015","unstructured":"Francino, M. P. Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances. Front Microbiol 6, 1543, https:\/\/doi.org\/10.3389\/fmicb.2015.01543 (2015).","journal-title":"Front Microbiol"},{"key":"33587_CR36","doi-asserted-by":"publisher","unstructured":"Stewart, P. S. Antimicrobial Tolerance in Biofilms. Microbiology spectrum 3, https:\/\/doi.org\/10.1128\/microbiolspec.MB-0010-2014 (2015).","DOI":"10.1128\/microbiolspec.MB-0010-2014"},{"key":"33587_CR37","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1021\/bc500094d","volume":"25","author":"ZZ Deris","year":"2014","unstructured":"Deris, Z. Z. et al. Probing the penetration of antimicrobial polymyxin lipopeptides into gram-negative bacteria. Bioconjugate chemistry 25, 750\u2013760, https:\/\/doi.org\/10.1021\/bc500094d (2014).","journal-title":"Bioconjugate chemistry"},{"key":"33587_CR38","doi-asserted-by":"publisher","first-page":"4494","DOI":"10.1128\/jb.00011-12","volume":"194","author":"J Pogliano","year":"2012","unstructured":"Pogliano, J., Pogliano, N. & Silverman, J. A. Daptomycin-Mediated Reorganization of Membrane Architecture Causes Mislocalization of Essential Cell Division Proteins. Journal of bacteriology 194, 4494\u20134504, https:\/\/doi.org\/10.1128\/jb.00011-12 (2012).","journal-title":"Journal of bacteriology"},{"key":"33587_CR39","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1074\/jbc.M115.691725","volume":"291","author":"M Urfer","year":"2016","unstructured":"Urfer, M. et al. A Peptidomimetic Antibiotic Targets Outer Membrane Proteins and Disrupts Selectively the Outer Membrane in Escherichia coli. Journal of Biological Chemistry 291, 1921\u20131932, https:\/\/doi.org\/10.1074\/jbc.M115.691725 (2016).","journal-title":"Journal of Biological Chemistry"},{"key":"33587_CR40","doi-asserted-by":"publisher","first-page":"e106967","DOI":"10.1371\/journal.pone.0106967","volume":"9","author":"K Brudzynski","year":"2014","unstructured":"Brudzynski, K. & Sjaarda, C. Antibacterial Compounds of Canadian Honeys Target Bacterial Cell Wall Inducing Phenotype Changes, Growth Inhibition and Cell Lysis That Resemble Action of \u03b2-Lactam Antibiotics. PLOS ONE 9, e106967, https:\/\/doi.org\/10.1371\/journal.pone.0106967 (2014).","journal-title":"PLOS ONE"},{"key":"33587_CR41","doi-asserted-by":"publisher","DOI":"10.1186\/s40064-015-1476-7","volume":"4","author":"S Halder","year":"2015","unstructured":"Halder, S. et al. Alteration of Zeta potential and membrane permeability in bacteria: a study with cationic agents. SpringerPlus 4, 672, https:\/\/doi.org\/10.1186\/s40064-015-1476-7 (2015).","journal-title":"SpringerPlus"},{"key":"33587_CR42","doi-asserted-by":"publisher","first-page":"4663","DOI":"10.1128\/aem.00643-16","volume":"82","author":"R Xue","year":"2016","unstructured":"Xue, R. et al. Shape Changes and Interaction Mechanism of Escherichia coli Cells Treated with Sericin and Use of a Sericin-Based Hydrogel for Wound Healing. Applied and Environmental Microbiology 82, 4663\u20134672, https:\/\/doi.org\/10.1128\/aem.00643-16 (2016).","journal-title":"Applied and Environmental Microbiology"},{"key":"33587_CR43","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.1128\/aac.00124-10","volume":"54","author":"M Hartmann","year":"2010","unstructured":"Hartmann, M. et al. Damage of the Bacterial Cell Envelope by Antimicrobial Peptides Gramicidin S and PGLa as Revealed by Transmission and Scanning Electron Microscopy. Antimicrobial Agents and Chemotherapy 54, 3132\u20133142, https:\/\/doi.org\/10.1128\/aac.00124-10 (2010).","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"33587_CR44","doi-asserted-by":"publisher","first-page":"e90228","DOI":"10.1371\/journal.pone.0090228","volume":"9","author":"D Zweytick","year":"2014","unstructured":"Zweytick, D. et al. N-acylated Peptides Derived from Human Lactoferricin Perturb Organization of Cardiolipin and Phosphatidylethanolamine in Cell Membranes and Induce Defects in Escherichia coli Cell Division. PLOS ONE 9, e90228, https:\/\/doi.org\/10.1371\/journal.pone.0090228 (2014).","journal-title":"PLOS ONE"},{"key":"33587_CR45","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-2-61","volume":"2","author":"S Yenugu","year":"2004","unstructured":"Yenugu, S., Hamil, K. G., French, F. S. & Hall, S. H. Antimicrobial actions of the human epididymis 2 (HE2) protein isoforms, HE2alpha, HE2beta1 and HE2beta2. Reproductive Biology and Endocrinology 2, 61, https:\/\/doi.org\/10.1186\/1477-7827-2-61 (2004).","journal-title":"Reproductive Biology and Endocrinology"},{"key":"33587_CR46","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1021\/bi501483q","volume":"54","author":"HR Chileveru","year":"2015","unstructured":"Chileveru, H. R. et al. Visualizing Attack of Escherichia coli by the Antimicrobial Peptide Human Defensin 5. Biochemistry 54, 1767\u20131777, https:\/\/doi.org\/10.1021\/bi501483q (2015).","journal-title":"Biochemistry"},{"key":"33587_CR47","doi-asserted-by":"publisher","unstructured":"Mojsoska, B., Carretero, G., Larsen, S., Mateiu, R. V. & Jenssen, H. Peptoids successfully inhibit the growth of gram negative E. coli causing substantial membrane damage. Scientific Reports 7, 42332, https:\/\/doi.org\/10.1038\/srep42332 https:\/\/www.nature.com\/articles\/srep42332#supplementary-information (2017).","DOI":"10.1038\/srep42332"},{"key":"33587_CR48","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.vetmic.2010.07.013","volume":"147","author":"NK Chanteloup","year":"2011","unstructured":"Chanteloup, N. K. et al. The extra-intestinal avian pathogenic Escherichia coli strain BEN2908 invades avian and human epithelial cells and survives intracellularly. Veterinary microbiology 147, 435\u2013439, https:\/\/doi.org\/10.1016\/j.vetmic.2010.07.013 (2011).","journal-title":"Veterinary microbiology"},{"key":"33587_CR49","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/978-1-4939-2272-7_3","volume":"1266","author":"NJ Yang","year":"2015","unstructured":"Yang, N. J. & Hinner, M. J. Getting Across the Cell Membrane: An Overview for Small Molecules, Peptides, and Proteins. Methods in molecular biology (Clifton, N.J.) 1266, 29\u201353, https:\/\/doi.org\/10.1007\/978-1-4939-2272-7_3 (2015).","journal-title":"Methods in molecular biology (Clifton, N.J.)"},{"key":"33587_CR50","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1128\/iai.00821-10","volume":"79","author":"S Wang","year":"2011","unstructured":"Wang, S. et al. Effects of ibeA Deletion on Virulence and Biofilm Formation of Avian Pathogenic Escherichia coli. Infection and immunity 79, 279\u2013287, https:\/\/doi.org\/10.1128\/iai.00821-10 (2011).","journal-title":"Infection and immunity"},{"key":"33587_CR51","doi-asserted-by":"publisher","first-page":"2360","DOI":"10.1128\/aem.02634-07","volume":"74","author":"TJ Johnson","year":"2008","unstructured":"Johnson, T. J., Wannemuehler, Y. M. & Nolan, L. K. Evolution of the iss Gene in Escherichia coli. Applied and Environmental Microbiology 74, 2360\u20132369, https:\/\/doi.org\/10.1128\/aem.02634-07 (2008).","journal-title":"Applied and Environmental Microbiology"},{"key":"33587_CR52","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1080\/21505594.2015.1135289","volume":"7","author":"CJ Tsai","year":"2016","unstructured":"Tsai, C. J., Loh, J. M. & Proft, T. Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing. Virulence 7, 214\u2013229, https:\/\/doi.org\/10.1080\/21505594.2015.1135289 (2016).","journal-title":"Virulence"},{"issue":"2","key":"33587_CR53","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1080\/14756360600563063","volume":"21","author":"Seza Arslan","year":"2006","unstructured":"Antimicrobial activity studies on some piperidine and pyrrolidine substituted halogenobenzene derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry 21, 211\u2013214, https:\/\/doi.org\/10.1080\/14756360600563063 (2006).","journal-title":"Journal of Enzyme Inhibition and Medicinal Chemistry"},{"key":"33587_CR54","doi-asserted-by":"publisher","first-page":"5073","DOI":"10.1016\/j.bmcl.2006.07.037","volume":"16","author":"ME Hensler","year":"2006","unstructured":"Hensler, M. E., Bernstein, G., Nizet, V. & Nefzi, A. Pyrrolidine bis-cyclic guanidines with antimicrobial activity against drug-resistant Gram-positive pathogens identified from a mixture-based combinatorial library. Bioorganic & medicinal chemistry letters 16, 5073\u20135079, https:\/\/doi.org\/10.1016\/j.bmcl.2006.07.037 (2006).","journal-title":"Bioorganic & medicinal chemistry letters"},{"key":"33587_CR55","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.2174\/13895575113136660091","volume":"13","author":"N Rani","year":"2013","unstructured":"Rani, N., Sharma, A. & Singh, R. Imidazoles as Promising Scaffolds for Antibacterial Activity: A Review. Mini Reviews in Medicinal Chemistry 13, 1812\u20131835 (2013).","journal-title":"Mini Reviews in Medicinal Chemistry"},{"key":"33587_CR56","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1155\/2013\/329412","volume":"2013","author":"A Verma","year":"2013","unstructured":"Verma, A., Joshi, S. & Singh, D. Imidazole: Having Versatile Biological Activities. Journal of Chemistry 2013, 12, https:\/\/doi.org\/10.1155\/2013\/329412 (2013).","journal-title":"Journal of Chemistry"},{"key":"33587_CR57","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1111\/j.1747-0285.2008.00691.x","volume":"72","author":"MS Khan","year":"2008","unstructured":"Khan, M. S. et al. Antibacterial Activity of Synthesized 2,4,5\u2010Trisubstituted Imidazole Derivatives. Chemical Biology & Drug Design 72, 197\u2013204, https:\/\/doi.org\/10.1111\/j.1747-0285.2008.00691.x (2008).","journal-title":"Chemical Biology & Drug Design"},{"key":"33587_CR58","doi-asserted-by":"publisher","first-page":"9222","DOI":"10.1002\/slct.201700692","volume":"2","author":"SA Egu","year":"2017","unstructured":"Egu, S. A., Ibezim, A., Onoabedje, E. A. & Okoro, U. C. Biological and In silico Evaluation of Quinolinedione and Naphthoquinone Derivatives as Potent Antibacterial Agents. Chemistry Select 2, 9222\u20139226, https:\/\/doi.org\/10.1002\/slct.201700692 (2017).","journal-title":"Chemistry Select"},{"key":"33587_CR59","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1039\/C5MD00503E","volume":"7","author":"M-P Mingeot-Leclercq","year":"2016","unstructured":"Mingeot-Leclercq, M.-P. & Decout, J.-L. 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. Med Chem Comm 7, 586\u2013611, https:\/\/doi.org\/10.1039\/C5MD00503E (2016).","journal-title":"Med Chem Comm"},{"key":"33587_CR60","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1021\/acs.biochem.6b01135","volume":"56","author":"AT Hubbard","year":"2017","unstructured":"Hubbard, A. T. et al. Mechanism of Action of a Membrane-Active Quinoline-Based Antimicrobial on Natural and Model Bacterial Membranes. Biochemistry 56, 1163\u20131174, https:\/\/doi.org\/10.1021\/acs.biochem.6b01135 (2017).","journal-title":"Biochemistry"},{"key":"33587_CR61","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1093\/clinids\/2.4.520","volume":"2","author":"M Borgers","year":"1980","unstructured":"Borgers, M. Mechanism of action of antifungal drugs, with special reference to the imidazole derivatives. Reviews of infectious diseases 2, 520\u2013534 (1980).","journal-title":"Reviews of infectious diseases"},{"key":"33587_CR62","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s11743-016-1906-8","volume":"20","author":"D Wieczorek","year":"2017","unstructured":"Wieczorek, D., Dobrowolski, A., Staszak, K., Kwa\u015bniewska, D. & Dubyk, P. Synthesis, Surface and Antimicrobial Activity of Piperidine-Based Sulfobetaines. Journal of Surfactants and Detergents 20, 151\u2013158, https:\/\/doi.org\/10.1007\/s11743-016-1906-8 (2017).","journal-title":"Journal of Surfactants and Detergents"},{"key":"33587_CR63","doi-asserted-by":"publisher","first-page":"17668","DOI":"10.3390\/ijms160817668","volume":"16","author":"D Wang","year":"2015","unstructured":"Wang, D. et al. Unveiling the Mode of Action of Two Antibacterial Tanshinone Derivatives. International Journal of Molecular Sciences 16, 17668\u201317681, https:\/\/doi.org\/10.3390\/ijms160817668 (2015).","journal-title":"International Journal of Molecular Sciences"},{"key":"33587_CR64","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1093\/jac\/44.5.641","volume":"44","author":"A Giacometti","year":"1999","unstructured":"Giacometti, A., Cirioni, O., Barchiesi, F., Fortuna, M. & Scalise, G. In-vitro activity of cationic peptides alone and in combination with clinically used antimicrobial agents against Pseudomonas aeruginosa. Journal of Antimicrobial Chemotherapy 44, 641\u2013645, https:\/\/doi.org\/10.1093\/jac\/44.5.641 (1999).","journal-title":"Journal of Antimicrobial Chemotherapy"},{"key":"33587_CR65","doi-asserted-by":"publisher","first-page":"A288","DOI":"10.1289\/ehp.118-a288","volume":"118","author":"C Potera","year":"2010","unstructured":"Potera, C. ANTIBIOTIC RESISTANCE: Biofilm Dispersing Agent Rejuvenates Older Antibiotics. Environmental Health Perspectives 118, A288\u2013A288 (2010).","journal-title":"Environmental Health Perspectives"},{"key":"33587_CR66","doi-asserted-by":"publisher","first-page":"647","DOI":"10.4155\/fmc.15.7","volume":"7","author":"N Rabin","year":"2015","unstructured":"Rabin, N. et al. Agents that inhibit bacterial biofilm formation. Future medicinal chemistry 7, 647\u2013671, https:\/\/doi.org\/10.4155\/fmc.15.7 (2015).","journal-title":"Future medicinal chemistry"},{"key":"33587_CR67","doi-asserted-by":"publisher","first-page":"2862","DOI":"10.3382\/ps\/pex088","volume":"96","author":"P Maharjan","year":"2017","unstructured":"Maharjan, P. et al. Effect of chlorine treatment on inhibition of E. coli serogroup O2 incorporation into 7-day-old biofilm on polyvinylchloride surface. Poultry science 96, 2862\u20132870, https:\/\/doi.org\/10.3382\/ps\/pex088 (2017).","journal-title":"Poultry science"},{"key":"33587_CR68","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1128\/aac.45.4.999-1007.2001","volume":"45","author":"K Lewis","year":"2001","unstructured":"Lewis, K. Riddle of Biofilm Resistance. Antimicrobial Agents and Chemotherapy 45, 999\u20131007, https:\/\/doi.org\/10.1128\/aac.45.4.999-1007.2001 (2001).","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"33587_CR69","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.fm.2015.10.010","volume":"54","author":"Y Yang","year":"2016","unstructured":"Yang, Y. et al. Biofilm formation of Salmonella Enteritidis under food-related environmental stress conditions and its subsequent resistance to chlorine treatment. Food Microbiology 54, 98\u2013105, https:\/\/doi.org\/10.1016\/j.fm.2015.10.010 (2016).","journal-title":"Food Microbiology"},{"key":"33587_CR70","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.bbamem.2015.10.018","volume":"1858","author":"RM Epand","year":"2016","unstructured":"Epand, R. M., Walker, C., Epand, R. F. & Magarvey, N. A. Molecular mechanisms of membrane targeting antibiotics. Biochimica et Biophysica Acta (BBA) - Biomembranes 1858, 980\u2013987, https:\/\/doi.org\/10.1016\/j.bbamem.2015.10.018 (2016).","journal-title":"Biochimica et Biophysica Acta (BBA) - Biomembranes"},{"key":"33587_CR71","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/S0022-2275(20)39729-7","volume":"36","author":"EJ Schaefer","year":"1995","unstructured":"Schaefer, E. J. et al. Red blood cell membrane phosphatidylethanolamine fatty acid content in various forms of retinitis pigmentosa. Journal of lipid research 36, 1427\u20131433 (1995).","journal-title":"Journal of lipid research"},{"key":"33587_CR72","doi-asserted-by":"publisher","first-page":"290","DOI":"10.5491\/SHAW.2011.2.3.290","volume":"2","author":"H-Y Kim","year":"2011","unstructured":"Kim, H.-Y., Kang, M.-G., Kim, T.-G. & Kang, C.-W. Toxicity of Methylcyclohexane and Its Effect on the Reproductive System in SD Rats. Safety and Health at Work 2, 290\u2013300, https:\/\/doi.org\/10.5491\/SHAW.2011.2.3.290 (2011).","journal-title":"Safety and Health at Work"},{"key":"33587_CR73","doi-asserted-by":"publisher","first-page":"67","DOI":"10.2174\/1389200003339270","volume":"1","author":"M Murray","year":"2000","unstructured":"Murray, M. Mechanisms of inhibitory and regulatory effects of methylenedioxyphenyl compounds on cytochrome P450-dependent drug oxidation. Current drug metabolism 1, 67\u201384 (2000).","journal-title":"Current drug metabolism"},{"key":"33587_CR74","doi-asserted-by":"publisher","unstructured":"Ramarao, N., Nielsen-Leroux, C. & Lereclus, D. The Insect Galleria mellonella as a Powerful Infection Model to Investigate Bacterial Pathogenesis. Journal of Visualized Experiments: JoVE, 4392, https:\/\/doi.org\/10.3791\/4392 (2012).","DOI":"10.3791\/4392"},{"key":"33587_CR75","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.ijms.2009.03.005","volume":"283","author":"J Gidden","year":"2009","unstructured":"Gidden, J., Denson, J., Liyanage, R., Ivey, D. M. & Lay, J. O. Lipid Compositions in Escherichia coli and Bacillus subtilis During Growth as Determined by MALDI-TOF and TOF\/TOF Mass Spectrometry. International journal of mass spectrometry 283, 178\u2013184, https:\/\/doi.org\/10.1016\/j.ijms.2009.03.005 (2009).","journal-title":"International journal of mass spectrometry"},{"key":"33587_CR76","doi-asserted-by":"publisher","first-page":"108","DOI":"10.4161\/gmic.26945","volume":"5","author":"D Pan","year":"2014","unstructured":"Pan, D. & Yu, Z. Intestinal microbiome of poultry and its interaction with host and diet. Gut microbes 5, 108\u2013119, https:\/\/doi.org\/10.4161\/gmic.26945 (2014).","journal-title":"Gut microbes"},{"key":"33587_CR77","doi-asserted-by":"publisher","first-page":"3531","DOI":"10.3390\/ijms10083531","volume":"10","author":"SM Lutful Kabir","year":"2009","unstructured":"Lutful Kabir, S. M. The Role of Probiotics in the Poultry Industry. International Journal of Molecular Sciences 10, 3531\u20133546, https:\/\/doi.org\/10.3390\/ijms10083531 (2009).","journal-title":"International Journal of Molecular Sciences"},{"key":"33587_CR78","doi-asserted-by":"crossref","unstructured":"Desbois, A. P. & Coote, P. J. In Advances in Applied Microbiology Vol. 78 (eds Allen I. Laskin, Sima Sariaslani, & Geoffrey M. Gadd) 25\u201353 (Academic Press, 2012).","DOI":"10.1016\/B978-0-12-394805-2.00002-6"},{"key":"33587_CR79","doi-asserted-by":"publisher","first-page":"388","DOI":"10.4161\/viru.27912","volume":"5","author":"DA Williamson","year":"2014","unstructured":"Williamson, D. A., Mills, G., Johnson, J. R., Porter, S. & Wiles, S. In vivo correlates of molecularly inferred virulence among extraintestinal pathogenic Escherichia coli (ExPEC) in the wax moth Galleria mellonella model system. Virulence 5, 388\u2013393, https:\/\/doi.org\/10.4161\/viru.27912 (2014).","journal-title":"Virulence"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-33587-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-33587-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-33587-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T10:32:42Z","timestamp":1671618762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-33587-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,17]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["33587"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-33587-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,17]]},"assertion":[{"value":"11 May 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"15329"}}