{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:48:42Z","timestamp":1777866522660,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad del Magdalena through Editorial Unimagdalena, Vicerrector\u00eda de Investigaci\u00f3n"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The antimicrobial resistance of Acinetobacter baumannii necessitates the development of novel therapeutic strategies targeting essential enzymes such as Undecaprenyl Pyrophosphate Phosphatase (UppP). This study explored spider venom peptides in silico as potential allosteric inhibitors of A. baumannii UppP. A systematic literature review was conducted to select eight \u03b1-helical peptides with reported anti-A. baumannii activity, followed by their computational physicochemical characterization. Three-dimensional models of A. baumannii UppP and the candidate peptides were generated, and a putative allosteric binding site was validated through molecular docking of a known inhibitor of the BacA homolog. The eight peptides were subsequently docked to this validated site using HADDOCK. Results revealed variable binding affinities; peptides LC-AMP-I1, Lycosin-II, and GK37 exhibited the most favorable HADDOCK scores and extensive interaction networks, consistent with their reported high antimicrobial potency. Other candidates, notably Lt-MAP2, showed low binding affinity but high predicted synergistic potential. These findings identify promising spider venom peptide candidates, suggesting dual (membrane disruption\/UppP inhibition) or synergistic mechanisms of action, and validate UppP as a viable pharmacological target for peptide-based inhibitors.<\/jats:p>","DOI":"10.3390\/toxins18050210","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:46:26Z","timestamp":1777538786000},"page":"210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spider Venom Peptides as Potential Allosteric Inhibitors of Undecaprenyl Diphosphatase (UppP) from Acinetobacter baumannii: In Silico Identification and Structural Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2674-8725","authenticated-orcid":false,"given":"Yamil","family":"Liscano","sequence":"first","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Salud Integral (GISI), Facultad de Salud, Universidad Santiago de Cali, Cali 760035, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-226X","authenticated-orcid":false,"given":"Juan M.","family":"\u00c1lvarez-Caballero","sequence":"additional","affiliation":[{"name":"Grupo de Quimica y Bioprospeccion de Productos Naturales (QUIBIP), Departamento de Qu\u00edmica, Universidad del Magdalena, Santa Marta 470004, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5554-9592","authenticated-orcid":false,"given":"Alberto","family":"Arag\u00f3n-Muriel","sequence":"additional","affiliation":[{"name":"Grupo de Quimica y Bioprospeccion de Productos Naturales (QUIBIP), Departamento de Qu\u00edmica, Universidad del Magdalena, Santa Marta 470004, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Coque, T.M., Cant\u00f3n, R., P\u00e9rez-Cobas, A.E., Fern\u00e1ndez-de-Bobadilla, M.D., and Baquero, F. (2023). Antimicrobial Resistance in the Global Health Network: Known Unknowns and Challenges for Efficient Responses in the 21st Century. Microorganisms, 11.","DOI":"10.3390\/microorganisms11041050"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Salam, M.A., Al-Amin, M.Y., Salam, M.T., Pawar, J.S., Akhter, N., Rabaan, A.A., and Alqumber, M.A.A. (2023). Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare, 11.","DOI":"10.20944\/preprints202305.0555.v1"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Scoffone, V.C., Trespidi, G., Barbieri, G., Arshad, A., Israyilova, A., and Buroni, S. (2025). The Evolution of Antimicrobial Resistance in Acinetobacter baumannii and New Strategies to Fight It. Antibiotics, 14.","DOI":"10.3390\/antibiotics14010085"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zwama, M., and Nishino, K. (2021). Ever-Adapting RND Efflux Pumps in Gram-Negative Multidrug-Resistant Pathogens: A Race against Time. Antibiotics, 10.","DOI":"10.3390\/antibiotics10070774"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Vrancianu, C.O., Gheorghe, I., Czobor, I.B., and Chifiriuc, M.C. (2020). Antibiotic Resistance Profiles, Molecular Mechanisms and Innovative Treatment Strategies of Acinetobacter baumannii. Microorganisms, 8.","DOI":"10.3390\/microorganisms8060935"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1016\/j.csbj.2022.05.010","article-title":"Towards Discovery of Inhibitors of the Undecaprenyl-Pyrophosphate Phosphatase BacA by Virtual High-Throughput Screening","volume":"20","author":"Auger","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30106","DOI":"10.1074\/jbc.M401701200","article-title":"The bacA Gene of Escherichia coli Encodes an Undecaprenyl Pyrophosphate Phosphatase Activity","volume":"279","author":"Bouhss","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Radeck, J., Lautenschl\u00e4ger, N., and Mascher, T. (2017). The Essential UPP Phosphatase Pair BcrC and UppP Connects Cell Wall Homeostasis during Growth and Sporulation with Cell Envelope Stress Response in Bacillus subtilis. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.02403"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1128\/JB.00507-16","article-title":"Depletion of Undecaprenyl Pyrophosphate Phosphatases Disrupts Cell Envelope Biogenesis in Bacillus subtilis","volume":"198","author":"Zhao","year":"2016","journal-title":"J. Bacteriol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1099\/mic.0.000142","article-title":"Identification and Characterization of SMU.244 Encoding a Putative Undecaprenyl Pyrophosphate Phosphatase Protein Required for Cell Wall Biosynthesis and Bacitracin Resistance in Streptococcus mutans","volume":"161","author":"Jalal","year":"2015","journal-title":"Microbiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1093\/jac\/dkt048","article-title":"Undecaprenyl Pyrophosphate Phosphatase Confers Low-Level Resistance to Bacitracin in Enterococcus faecalis","volume":"68","author":"Shaaly","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gasiorowski, E., Auger, R., Tian, X., Hicham, S., Ecobichon, C., Roure, S., Douglass, M.V., Trent, M.S., Mengin-Lecreulx, D., and Touz\u00e9, T. (2019). HupA, the Main Undecaprenyl Pyrophosphate and Phosphatidylglycerol Phosphate Phosphatase in Helicobacter pylori Is Essential for Colonization of the Stomach. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007972"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/s41467-018-03547-8","article-title":"Crystal Structure of an Intramembranal Phosphatase Central to Bacterial Cell-Wall Peptidoglycan Biosynthesis and Lipid Recycling","volume":"9","author":"Workman","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41467-018-03477-5","article-title":"Crystal Structure of Undecaprenyl-Pyrophosphate Phosphatase and Its Role in Peptidoglycan Biosynthesis","volume":"9","author":"Howe","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"14207","DOI":"10.1073\/pnas.1308268110","article-title":"High-Resolution Crystal Structure Reveals Molecular Details of Target Recognition by Bacitracin","volume":"110","author":"Economou","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1089\/mdr.2014.0035","article-title":"Deciphering the Metabolism of Undecaprenyl-Phosphate: The Bacterial Cell-Wall Unit Carrier at the Membrane Frontier","volume":"20","author":"Manat","year":"2014","journal-title":"Microb. Drug Resist."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/mmi.13336","article-title":"Anatomy of the Bacitracin Resistance Network in Bacillus subtilis","volume":"100","author":"Radeck","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2315310121","DOI":"10.1073\/pnas.2315310121","article-title":"A Classic Antibiotic Reimagined: Rationally Designed Bacitracin Variants Exhibit Potent Activity against Vancomycin-Resistant Pathogens","volume":"121","author":"Buijs","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Liscano, Y., O\u00f1ate-Garz\u00f3n, J., and Delgado, J.P. (2020). Peptides with Dual Antimicrobial\u2013Anticancer Activity: Strategies to Overcome Peptide Limitations and Rational Design of Anticancer Peptides. Molecules, 25.","DOI":"10.3390\/molecules25184245"},{"key":"ref_20","first-page":"1573","article-title":"Antimicrobial Peptides (AMPs): A Promising Class of Antimicrobial Compounds","volume":"132","author":"Kesmen","year":"2021","journal-title":"J. Appl. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e00424-24","DOI":"10.1128\/aac.00424-24","article-title":"LC-AMP-I1, a Novel Venom-Derived Antimicrobial Peptide from the Wolf Spider Lycosa coelestis","volume":"69","author":"Wang","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Tan, H., Wang, J., Song, Y., Liu, S., Lu, Z., Luo, H., and Tang, X. (2022). Antibacterial Potential Analysis of Novel \u03b1-Helix Peptides in the Chinese Wolf Spider Lycosa sinensis. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14112540"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wang, L., Yang, H., Xiao, H., Farooq, A., Liu, Z., Hu, M., and Shi, X. (2016). The Spider Venom Peptide Lycosin-II Has Potent Antimicrobial Activity against Clinically Isolated Bacteria. Toxins, 8.","DOI":"10.3390\/toxins8050119"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Shin, M.K., Hwang, I.-W., Kim, Y., Kim, S.T., Jang, W., Lee, S., Bang, W.Y., Bae, C.-H., and Sung, J.-S. (2020). Antibacterial and Anti-Inflammatory Effects of Novel Peptide Toxin from the Spider Pardosa astrigera. Antibiotics, 9.","DOI":"10.3390\/antibiotics9070422"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1021\/acschembio.7b00459","article-title":"Redesigned Spider Peptide with Improved Antimicrobial and Anticancer Properties","volume":"12","author":"Lawrence","year":"2017","journal-title":"ACS Chem. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"De Moraes, L.F.R.N., Silva, P.S.E., Pereira, T.C.P.L., Almeida Rodrigues, T.A., Farias Frihling, B.E., Da Costa, R.A., Torquato, H.F.V., Lima, C.S., Paredes-Gamero, E.J., and Migliolo, L. (2022). First Generation of Multifunctional Peptides Derived from Latarcin-3a from Lachesana tarabaevi Spider Toxin. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.965621"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, K., Mwangi, J., Cao, K., Wang, Y., Gao, J., Yang, M., Michira, B.B., Lu, Q., and Li, J. (2024). Peptide Toxin Diversity and a Novel Antimicrobial Peptide from the Spider Oxyopes forcipiformis. Toxins, 16.","DOI":"10.3390\/toxins16110466"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"900","DOI":"10.2174\/15665240113139990045","article-title":"Antimicrobial Potential of Lycosin-I, a Cationic and Amphiphilic Peptide from the Venom of the Spider Lycosa singorensis","volume":"13","author":"Tan","year":"2013","journal-title":"Curr. Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eaau5480","DOI":"10.1126\/science.aau5480","article-title":"Antimicrobial Peptides: Application Informed by Evolution","volume":"368","author":"Lazzaro","year":"2020","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6999","DOI":"10.1128\/AAC.03279-14","article-title":"In Vitro Potential of Lycosin-I as an Alternative Antimicrobial Drug for Treatment of Multidrug-Resistant Acinetobacter baumannii Infections","volume":"58","author":"Wang","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biochi.2025.07.019","article-title":"Advancing Antimicrobial Peptides: Overcoming Challenges in the Era of Bacterial Resistance","volume":"238","author":"Aunpad","year":"2025","journal-title":"Biochimie"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e1230","DOI":"10.1002\/cl2.1230","article-title":"PRISMA2020: An R Package and Shiny App for Producing PRISMA 2020-Compliant Flow Diagrams, with Interactivity for Optimised Digital Transparency and Open Synthesis","volume":"18","author":"Haddaway","year":"2022","journal-title":"Campbell Syst. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","article-title":"MolProbity: More and Better Reference Data for Improved All-Atom Structure Validation","volume":"27","author":"Williams","year":"2018","journal-title":"Protein Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkw329","article-title":"PEP-FOLD3: Faster de Novo Structure Prediction for Linear Peptides in Solution and in Complex","volume":"44","author":"Lamiable","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-Web: Interactive Web Service for the Recognition of Errors in Three-Dimensional Structures of Proteins","volume":"35","author":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1021\/ja026939x","article-title":"HADDOCK: A Protein-Protein Docking Approach Based on Biochemical or Biophysical Information","volume":"125","author":"Dominguez","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jmb.2015.09.014","article-title":"The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes","volume":"428","author":"Rodrigues","year":"2016","journal-title":"J. Mol. Biol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/5\/210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:49:29Z","timestamp":1777538969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/5\/210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":37,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["toxins18050210"],"URL":"https:\/\/doi.org\/10.3390\/toxins18050210","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]}}}