title: Sequence-activity relationship, and mechanism of action of mastoparan analogues against extended-drug resistant Acinetobacter baumannii.
abstract: The treatment of some infectious diseases can currently be very challenging since the spread of multi-, extended- or pan-resistant bacteria has considerably increased over time. On the other hand, the number of new antibiotics approved by the FDA has decreased drastically over the last 30 years. The main objective of this study was to investigate the activity of wasp peptides, specifically mastoparan and some of its derivatives against extended-resistant Acinetobacter baumannii. We optimized the stability of mastoparan in human serum since the specie obtained after the action of the enzymes present in human serum is not active. Thus, 10 derivatives of mastoparan were synthetized. Mastoparan analogues (guanidilated at the N-terminal, enantiomeric version and mastoparan with an extra positive charge at the C-terminal) showed the same activity against Acinetobacter baumannii as the original peptide (2.7 μM) and maintained their stability to more than 24 h in the presence of human serum compared to the original compound. The mechanism of action of all the peptides was carried out using a leakage assay. It was shown that mastoparan and the abovementioned analogues were those that released more carboxyfluorescein. In addition, the effect of mastoparan and its enantiomer against A. baumannii was studied using transmission electron microscopy (TEM). These results suggested that several analogues of mastoparan could be good candidates in the battle against highly resistant A. baumannii infections since they showed good activity and high stability.
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Vila-Farrés
authors.affiliation: Biomedical Institute of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: López-Rojas
authors.affiliation: Biomedical Institute of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Pachón-Ibáñez
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Teixidó
authors.affiliation: Biomedical Institute of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Pachón
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain; Department of Clinical Microbiology, CDB, Hospital Clinic, School of Medicine, University of Barcelona, Barcelona, Spain. Electronic address: jvila@ub.edu.
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain; Department of Organic Chemistry, University of Barcelona, Barcelona, Spain. Electronic address: ernest.giralt@irbbarcelona.org.
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
mesh_terms: D040981:Acinetobacter baumannii / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival; D003091:Colistin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014862:Wasp Venoms / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; C037500:mastoparan; D003091:Colistin
keywords: Acinetobacter baumannii; Antimicrobial peptide; Mastoparan; Peptide