{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:45:07Z","timestamp":1779291907404,"version":"3.51.4"},"reference-count":92,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T00:00:00Z","timestamp":1703980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Joint Warfighter award","award":["W81XWH-21-1-0214"],"award-info":[{"award-number":["W81XWH-21-1-0214"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Acinetobacter baumannii is a gram-negative bacterium that causes hospital-acquired and opportunistic infections, resulting in pneumonia, sepsis, and severe wound infections that can be difficult to treat due to antimicrobial resistance and the formation of biofilms. There is an urgent need to develop novel antimicrobials to tackle the rapid increase in antimicrobial resistance, and antimicrobial peptides (AMPs) represent an additional class of potential agents with direct antimicrobial and\/or host-defense activating activities. In this study, we present GATR-3, a synthetic, designed AMP that was modified from a cryptic peptide discovered in American alligator, as our lead peptide to target multidrug-resistant (MDR) A. baumannii. Antimicrobial susceptibility testing and antibiofilm assays were performed to assess GATR-3 against a panel of 8 MDR A. baumannii strains, including AB5075 and some clinical strains. The GATR-3 mechanism of action was determined to be via loss of membrane integrity as measured by DiSC3(5) and ethidium bromide assays. GATR-3 exhibited potent antimicrobial activity against all tested multidrug-resistant A. baumannii strains with rapid killing. Biofilms are difficult to treat and eradicate. Excitingly, GATR-3 inhibited biofilm formation and, more importantly, eradicated preformed biofilms of MDR A. baumannii AB5075, as evidenced by MBEC assays and scanning electron micrographs. GATR3 did not induce resistance in MDR A. baumannii, unlike colistin. Additionally, the toxicity of GATR-3 was evaluated using human red blood cells, HepG2 cells, and waxworms using hemolysis and MTT assays. GATR-3 demonstrated little to no cytotoxicity against HepG2 and red blood cells, even at 100 \u03bcg\/mL. GATR-3 injection showed little toxicity in the waxworm model, resulting in a 90% survival rate. The therapeutic index of GATR-3 was estimated (based on the HC50\/MIC against human RBCs) to be 1250. Overall, GATR-3 is a promising candidate to advance to preclinical testing to potentially treat MDR A. baumannii infections.<\/jats:p>","DOI":"10.3390\/antibiotics13010039","type":"journal-article","created":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T06:00:21Z","timestamp":1704002421000},"page":"39","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["GATR-3, a Peptide That Eradicates Preformed Biofilms of Multidrug-Resistant Acinetobacter baumannii"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1679-4899","authenticated-orcid":false,"given":"Monique L.","family":"van Hoek","sequence":"first","affiliation":[{"name":"Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA"},{"name":"School of Systems Biology, George Mason University, Manassas, VA 20110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8343-6077","authenticated-orcid":false,"given":"Fahad M.","family":"Alsaab","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA"},{"name":"School of Systems Biology, George Mason University, Manassas, VA 20110, USA"},{"name":"College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Al Ahsa 36428, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley M.","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA"},{"name":"School of Systems Biology, George Mason University, Manassas, VA 20110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1056\/NEJM196610202751607","article-title":"Infectious drug resistance in enteric bacteria","volume":"275","author":"Watanabe","year":"1966","journal-title":"N. Engl. J. Med."},{"key":"ref_2","unstructured":"World Health Organization (2023, November 26). Available online: https:\/\/reliefweb.int\/report\/world\/antimicrobial-resistance-global-report-surveillance-2014?psafe_param=1&gad_source=1&gclid=CjwKCAiAnL-sBhBnEiwAJRGigq9cQaDP-5dZVIxsBKj61dBTKqubc10Egc9-BuDgnMuW5dypQJAiUhoCciQQAvD_BwE."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1128\/CMR.00058-07","article-title":"Acinetobacter baumannii: Emergence of a successful pathogen","volume":"21","author":"Peleg","year":"2008","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.4161\/viru.19700","article-title":"Acinetobacter baumannii: An emerging opportunistic pathogen","volume":"3","author":"Howard","year":"2012","journal-title":"Virulence"},{"key":"ref_5","unstructured":"(2019). Antibiotic Resistance Threats in the United States, CDC."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1086\/502046","article-title":"An outbreak due to multiresistant Acinetobacter baumannii in a burn unit: Risk factors for acquisition and management","volume":"23","author":"Simor","year":"2002","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1128\/CMR.9.2.148","article-title":"Acinetobacter spp. as nosocomial pathogens: Microbiological, clinical, and epidemiological features","volume":"9","author":"Towner","year":"1996","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/PRS.0b013e3181773d19","article-title":"War Wounds: Lessons Learned from Operation Iraqi Freedom","volume":"122","author":"Geiger","year":"2008","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/scientificamerican0178-86","article-title":"How Bacteria Stick","volume":"238","author":"Costerton","year":"1978","journal-title":"Sci. Am."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Akers, K.S., Mende, K., Cheatle, K.A., Zera, W.C., Yu, X., Beckius, M.L., Aggarwal, D., Li, P., Sanchez, C.J., and Wenke, J.C. (2014). Biofilms and persistent wound infections in United States military trauma patients: A case\u2013control analysis. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-190"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3389\/fimmu.2013.00143","article-title":"The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds","volume":"4","author":"Duplantier","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrmicro2415","article-title":"The biofilm matrix","volume":"8","author":"Flemming","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1086\/424846","article-title":"Diagnosis and Treatment of Diabetic Foot Infections","volume":"39","author":"Lipsky","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","first-page":"441","article-title":"The bacteriology of diabetic foot ulcers, with a special reference to multidrug resistant strains","volume":"7","author":"Shanmugam","year":"2013","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.2147\/DMSO.S296484","article-title":"Microbiological concordance in the management of diabetic foot ulcer infections with osteomyelitis, on the basis of cultures of different specimens at a diabetic foot center in China","volume":"14","author":"Li","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Macdonald, K.E., Boeckh, S., Stacey, H.J., and Jones, J.D. (2021). The microbiology of diabetic foot infections: A meta-analysis. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06516-7"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.5897\/AJMR2013.6548","article-title":"Prevalence of metallo-beta-lactamases producers among carbapenem-resistant Acinetobacter baumannii strains isolated from diabetic foot ulcers","volume":"8","year":"2014","journal-title":"Afr. J. Microbiol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Henig, O., Pogue, J.M., Martin, E., Hayat, U., Ja\u2019ara, M., Kilgore, P.E., Cha, R., Dhar, S., and Kaye, K.S. (2020). The Impact of Multidrug-Resistant Organisms on Outcomes in Patients With Diabetic Foot Infections. Open Forum Infect. Dis., 7.","DOI":"10.1093\/ofid\/ofaa161"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/nbt1267","article-title":"Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies","volume":"24","author":"Hancock","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Browne, K., Chakraborty, S., Chen, R., Willcox, M.D., Black, D.S., Walsh, W.R., and Kumar, N. (2020). A New Era of Antibiotics: The Clinical Potential of Antimicrobial Peptides. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197047"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4282","DOI":"10.1021\/acs.jproteome.5b00447","article-title":"Large Scale Discovery and De Novo-Assisted Sequencing of Cationic Antimicrobial Peptides (CAMPs) by Microparticle Capture and Electron-Transfer Dissociation (ETD) Mass Spectrometry","volume":"14","author":"Juba","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jtbi.2017.02.012","article-title":"Antimicrobial potency of cationic antimicrobial peptides can be predicted from their amino acid composition: Application to the detection of \u201ccryptic\u201d antimicrobial peptides","volume":"419","author":"Pane","year":"2017","journal-title":"J. Theor. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bishop, B.M., Juba, M.L., Devine, M.C., Barksdale, S.M., Rodriguez, C.A., Chung, M.C., Russo, P.S., Vliet, K.A., Schnur, J.M., and van Hoek, M.L. (2015). Bioprospecting the American alligator (Alligator mississippiensis) host defense peptidome. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117394"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Barksdale, S.M., Hrifko, E.J., Chung, E.M., and van Hoek, M.L. (2016). Peptides from American alligator plasma are antimicrobial against multi-drug resistant bacterial pathogens including Acinetobacter baumannii. BMC Microbiol., 16.","DOI":"10.1186\/s12866-016-0799-z"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"van Hoek, M.L., Kaushal, A., Bishop, B.M., and Barksdale, S.M. (2019). Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonary Francisella infection. bioRxiv.","DOI":"10.1101\/603233"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W174","DOI":"10.1093\/nar\/gkv342","article-title":"I-TASSER server: New development for protein structure and function predictions","volume":"43","author":"Yang","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"D1087","DOI":"10.1093\/nar\/gkv1278","article-title":"APD3: The antimicrobial peptide database as a tool for research and education","volume":"44","author":"Wang","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_28","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2023, November 26). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard-Tenth Edition. CLSI Document M07-A10 (ISBN 1-56238-987-4 [Print]: ISBN 1-56238-988-2 [Electronic]). Available online: https:\/\/clsi.org\/media\/1632\/m07a10_sample.pdf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e01076-01014","DOI":"10.1128\/mBio.01076-14","article-title":"AB5075, a Highly Virulent Isolate of Acinetobacter baumannii, as a Model Strain for the Evaluation of Pathogenesis and Antimicrobial Treatments","volume":"5","author":"Jacobs","year":"2014","journal-title":"mBio"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zhao, J., Han, M.-L., Zhu, Y., Lin, Y.-W., Wang, Y.-W., Lu, J., Hu, Y., Tony Zhou, Q., Velkov, T., and Li, J. (2021). Comparative metabolomics reveals key pathways associated with the synergistic activity of polymyxin B and rifampicin combination against multidrug-resistant Acinetobacter baumannii. Biochem. Pharmacol., 184.","DOI":"10.1016\/j.bcp.2020.114400"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Alsaab, F.M., Dean, S.N., Bobde, S., Ascoli, G.G., and van Hoek, M.L. (2023). Computationally Designed AMPs with Antibacterial and Antibiofilm Activity against MDR Acinetobacter baumannii. Antibiotics, 12.","DOI":"10.3390\/antibiotics12091396"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jmii.2019.08.008","article-title":"Vancomycin-loaded oxidized hyaluronic acid and adipic acid dihydrazide hydrogel: Bio-compatibility, drug release, antimicrobial activity, and biofilm model","volume":"53","author":"Liao","year":"2020","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"870","DOI":"10.3201\/eid1906.121515","article-title":"New Delhi metallo-\u03b2-lactamase\u2013producing enterobacteriaceae, United States","volume":"19","author":"Rasheed","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1097\/00002480-200011000-00037","article-title":"Role of Biofilms in Antimicrobial Resistance","volume":"46","author":"Donlan","year":"2000","journal-title":"ASAIO J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev.mi.41.100187.002251","article-title":"Bacterial Biofilms in Nature and Disease","volume":"41","author":"Costerton","year":"1987","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4939-6737-7_1","article-title":"Antimicrobial Peptides: An Introduction","volume":"1548","author":"Haney","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_37","first-page":"100131","article-title":"Factors mediating Acinetobacter baumannii biofilm formation: Opportunities for developing therapeutics","volume":"3","author":"Upmanyu","year":"2022","journal-title":"Curr. Res. Microb. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yang, C.-H., Su, P.-W., Moi, S.-H., and Chuang, L.-Y. (2019). Biofilm Formation in Acinetobacter Baumannii: Genotype-Phenotype Correlation. Molecules, 24.","DOI":"10.3390\/molecules24101849"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Dean, S.N., Bishop, B.M., and van Hoek, M.L. (2011). Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-114"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Dean, S.N., Bishop, B.M., and van Hoek, M.L. (2011). Susceptibility of Pseudomonas aeruginosa Biofilm to Alpha-Helical Peptides: D-enantiomer of LL-37. Front. Microbiol., 2.","DOI":"10.3389\/fmicb.2011.00128"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4176","DOI":"10.1128\/IAI.00318-08","article-title":"Human host defense peptide LL-37 prevents bacterial biofilm formation","volume":"76","author":"Overhage","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"de la Fuente-N\u00fa\u00f1ez, C., Reffuveille, F., Haney, E.F., Straus, S.K., and Hancock, R.E.W. (2014). Broad-Spectrum Anti-biofilm Peptide That Targets a Cellular Stress Response. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004152"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.diagmicrobio.2019.01.016","article-title":"Biofilm prevention concentrations (BPC) of minocycline compared to polymyxin B, meropenem, and amikacin against Acinetobacter baumannii","volume":"94","author":"Beganovic","year":"2019","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Haney, E.F., Trimble, M.J., Cheng, J.T., Valle, Q., and Hancock, R.E.W. (2018). Critical Assessment of Methods to Quantify Biofilm Growth and Evaluate Antibiofilm Activity of Host Defence Peptides. Biomolecules, 8.","DOI":"10.3390\/biom8020029"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.peptides.2013.09.007","article-title":"The human antimicrobial peptide LL-37 and its fragments possess both antimicrobial and antibiofilm activities against multidrug-resistant Acinetobacter baumannii","volume":"49","author":"Feng","year":"2013","journal-title":"Peptides"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Guo, Y., Wang, L., Lei, J., Xu, J., and Han, L. (2017). Antimicrobial and Antibiofilm Activity of Human Cationic Antibacterial Peptide (LL-37) and Its Analogs Against Pan-Drug-Resistant Acinetobacter baumannii. Jundishapur J. Microbiol., 10.","DOI":"10.5812\/jjm.35857"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"eaan4044","DOI":"10.1126\/scitranslmed.aan4044","article-title":"The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms","volume":"10","author":"Riool","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.1128\/AAC.00824-07","article-title":"Bactericidal action of daptomycin against stationary-phase and nondividing Staphylococcus aureus cells","volume":"51","author":"Mascio","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sanchez-Gomez, S., Ferrer-Espada, R., Stewart, P.S., Pitts, B., Lohner, K., and Martinez de Tejada, G. (2015). Antimicrobial activity of synthetic cationic peptides and lipopeptides derived from human lactoferricin against Pseudomonas aeruginosa planktonic cultures and biofilms. BMC Microbiol., 15.","DOI":"10.1186\/s12866-015-0473-x"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"26516","DOI":"10.1073\/pnas.1909585117","article-title":"The antimicrobial peptide ZY4 combats multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii infection","volume":"116","author":"Mwangi","year":"2019","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1038\/s41587-019-0222-z","article-title":"Design of stapled antimicrobial peptides that are stable, nontoxic and kill antibiotic-resistant bacteria in mice","volume":"37","author":"Mourtada","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.bbamem.2015.11.003","article-title":"The human cathelicidin LL-37\u2014A pore-forming antibacterial peptide and host-cell modulator","volume":"1858","author":"Xhindoli","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"13723","DOI":"10.1021\/bi9620621","article-title":"Membrane Pores Induced by Magainin","volume":"35","author":"Ludtke","year":"1996","journal-title":"Biochemistry"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Torres, M.D.T., Melo, M.C.R., Flowers, L., Crescenzi, O., Notomista, E., and de la Fuente-Nunez, C. (2022). Author Correction: Mining for encrypted peptide antibiotics in the human proteome. Nat. Biomed. Eng., 6.","DOI":"10.1038\/s41551-022-00967-2"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.dci.2017.01.011","article-title":"Cathelicidin antimicrobial peptide from Alligator mississippiensis has antibacterial activity against multi-drug resistant Acinetobacter baumanii and Klebsiella pneumoniae","volume":"70","author":"Barksdale","year":"2017","journal-title":"Dev. Comp. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1099\/jmm.0.001260","article-title":"Komodo-dragon cathelicidin-inspired peptides are antibacterial against carbapenem-resistant Klebsiella pneumoniae","volume":"69","author":"Hitt","year":"2020","journal-title":"J. Med. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"358","DOI":"10.3390\/antibiotics4030358","article-title":"Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics","volume":"4","author":"Gupta","year":"2015","journal-title":"Antibiotics"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Blower, R.J., Barksdale, S.M., and van Hoek, M.L. (2015). Snake Cathelicidin NA-CATH and Smaller Helical Antimicrobial Peptides Are Effective against Burkholderia thailandensis. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003862"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7213","DOI":"10.1128\/JB.00973-07","article-title":"PhoPQ-mediated regulation produces a more robust permeability barrier in the outer membrane of Salmonella enterica serovar typhimurium","volume":"189","author":"Murata","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1038\/s41598-020-59071-7","article-title":"Studies on citrullinated LL-37: Detection in human airways, antibacterial effects and biophysical properties","volume":"10","author":"Wallin","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Propst, C.N., Pylypko, S.L., Blower, R.J., Ahmad, S., Mansoor, M., and van Hoek, M.L. (2016). Francisella philomiragia Infection and Lethality in Mammalian Tissue Culture Cell Models, Galleria mellonella, and BALB\/c Mice. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00696"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wong, F., Zheng, E.J., Valeri, J.A., Donghia, N.M., Anahtar, M.N., Omori, S., Li, A., Cubillos-Ruiz, A., Krishnan, A., and Jin, W. (2023). Discovery of a structural class of antibiotics with explainable deep learning. Nature.","DOI":"10.1038\/s41586-023-06887-8"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Bobde, S.S., Alsaab, F.M., Wang, G., and Van Hoek, M.L. (2021). Ab initio Designed Antimicrobial Peptides Against Gram-Negative Bacteria. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.715246"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41420-022-00816-w","article-title":"Cathelicidin hCAP18\/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)(2)D(3) in hepatocellular carcinoma","volume":"8","author":"Zhang","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chung, E.M.C., Dean, S.N., Propst, C.N., Bishop, B.M., and van Hoek, M.L. (2017). Komodo dragon-inspired synthetic peptide DRGN-1 promotes wound-healing of a mixed-biofilm infected wound. NPJ Biofilms Microbiomes, 3.","DOI":"10.1038\/s41522-017-0017-2"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"366","DOI":"10.3390\/ph7040366","article-title":"\u201cSpecificity Determinants\u201d Improve Therapeutic Indices of Two Antimicrobial Peptides Piscidin 1 and Dermaseptin S4 Against the Gram-negative Pathogens Acinetobacter baumannii and Pseudomonas aeruginosa","volume":"7","author":"Jiang","year":"2014","journal-title":"Pharmaceuticals"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12316","DOI":"10.1074\/jbc.M413406200","article-title":"Rational design of alpha-helical antimicrobial peptides with enhanced activities and specificity\/therapeutic index","volume":"280","author":"Chen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10989-014-9430-z","article-title":"Cationic Antimicrobial Peptides Cytotoxicity on Mammalian Cells: An Analysis Using Therapeutic Index Integrative Concept","volume":"21","author":"Bacalum","year":"2015","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nrd3801","article-title":"The determination and interpretation of the therapeutic index in drug development","volume":"11","author":"Muller","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ajic.2011.03.025","article-title":"Longitudinal characterization of Acinetobacter baumannii-calcoaceticus complex, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus colonizing and infecting combat casualties","volume":"40","author":"Sensenig","year":"2012","journal-title":"Am. J. Infect. Control"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e00026-14","DOI":"10.1128\/genomeA.00026-14","article-title":"Genome Sequences of Four Acinetobacter baumannii-A. calcoaceticus Complex Isolates from Combat-Related Infections Sustained in the Middle East","volume":"2","author":"Ketter","year":"2014","journal-title":"Genome Announc."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.284.5418.1318","article-title":"Bacterial Biofilms: A Common Cause of Persistent Infections","volume":"284","author":"Costerton","year":"1999","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1099\/jmm.0.000032","article-title":"Healthcare-associated infections, medical devices and biofilms: Risk, tolerance and control","volume":"64","author":"Percival","year":"2015","journal-title":"J. Med. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1128\/AAC.04773-14","article-title":"In Vitro Spectrum of Pexiganan Activity When Tested against Pathogens from Diabetic Foot Infections and with Selected Resistance Mechanisms","volume":"59","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Gomes, D., Santos, R., Soares, R.S., Reis, S., Carvalho, S., Rego, P., Peleteiro, M.C., Tavares, L., and Oliveira, M. (2020). Pexiganan in Combination with Nisin to Control Polymicrobial Diabetic Foot Infections. Antibiotics, 9.","DOI":"10.3390\/antibiotics9030128"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s12602-018-9444-5","article-title":"Antimicrobial Activity of Selected Antimicrobial Peptides Against Planktonic Culture and Biofilm of Acinetobacter baumannii","volume":"11","author":"Neubauer","year":"2019","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.bbamem.2015.02.001","article-title":"Antimicrobial properties of membrane-active dodecapeptides derived from MSI-78","volume":"1848","author":"Monteiro","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1007\/s00403-023-02657-8","article-title":"Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: A randomized double-blind controlled trial","volume":"315","author":"Miranda","year":"2023","journal-title":"Arch. Dermatol. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1089\/wound.2018.0786","article-title":"A Porcine Wound Model of Acinetobacter baumannii Infection","volume":"8","author":"Zurawski","year":"2019","journal-title":"Adv. Wound Care"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nprot.2007.521","article-title":"Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances","volume":"3","author":"Wiegand","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Sato, Y., Unno, Y., Ubagai, T., and Ono, Y. (2018). Sub-minimum inhibitory concentrations of colistin and polymyxin B promote Acinetobacter baumannii biofilm formation. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194556"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Lee, B., Shin, M.K., Yoo, J.S., Jang, W., and Sung, J.-S. (2022). Identifying novel antimicrobial peptides from venom gland of spider Pardosa astrigera by deep multi-task learning. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.971503"},{"key":"ref_83","first-page":"26","article-title":"Spot plating assay for the determination of survival and plating efficiency of Escherichia coli in sub-MIC levels of antibiotics","volume":"1","author":"Wang","year":"2017","journal-title":"JEMI Methods"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s00248-009-9586-9","article-title":"Francisella novicida Forms In Vitro Biofilms Mediated by an Orphan Response Regulator","volume":"59","author":"Verhoeven","year":"2010","journal-title":"Microb. Ecol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"890955","DOI":"10.3389\/fphar.2022.890955","article-title":"In Vitro Activity of Peptide Antibiotics in Combination With Other Antimicrobials on Extensively Drug-Resistant Acinetobacter baumannii in the Planktonic and Biofilm Cell","volume":"13","author":"Meng","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_86","unstructured":"Innovotech (2023, November 26). MBEC Assay\u00ae For High-Throughput Antimicrobial Susceptibility Testing of Biofilms PROCEDURAL MANUAL Version 2.1. Available online: https:\/\/innovotech.ca\/wp-content\/uploads\/2020\/01\/MBEC-Procedural-Manual-v2_1-3.pdf."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4365","DOI":"10.1038\/s41598-022-08247-4","article-title":"A novel hybrid peptide composed of LfcinB6 and KR-12-a4 with enhanced antimicrobial, anti-inflammatory and anti-biofilm activities","volume":"12","author":"Ajish","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1021\/acsinfecdis.1c00222","article-title":"Membrane-Permeable Antibacterial Enzyme against Multidrug-Resistant Acinetobacter baumannii","volume":"7","author":"Chen","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_89","first-page":"42","article-title":"Conventional scanning electron microscopy of bacteria","volume":"10","author":"Yang","year":"2008","journal-title":"Infocus Mag."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.bbrc.2016.01.100","article-title":"Characterization of Cimex lectularius (bedbug) defensin peptide and its antimicrobial activity against human skin microflora","volume":"470","author":"Kaushal","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1074\/jbc.274.1.29","article-title":"Interaction of the cyclic antimicrobial cationic peptide bactenecin with the outer and cytoplasmic membrane","volume":"274","author":"Wu","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1128\/iai.57.7.2187-2195.1989","article-title":"Induction of inflammatory mediators (histamine and leukotrienes) from rat peritoneal mast cells and human granulocytes by Pseudomonas aeruginosa strains from burn patients","volume":"57","author":"Bergmann","year":"1989","journal-title":"Infect. Immun."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/1\/39\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:45:09Z","timestamp":1760132709000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/1\/39"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,31]]},"references-count":92,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["antibiotics13010039"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics13010039","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,31]]}}}