title: Synthesis, characterization, and photoinduced antibacterial activity of porphyrin-type photosensitizers conjugated to the antimicrobial peptide apidaecin 1b.
abstract: Antimicrobial photodynamic therapy (aPDT) is an emerging treatment for bacterial infections that is becoming increasingly more attractive because of its effectiveness against multi-antibiotic-resistant strains and unlikelihood of inducing bacterial resistance. Among the strategies to enhance the efficacy of PDT against Gram-negative bacteria, the binding to a cationic antimicrobial peptide offers the attractive prospect for improving both the water solubilty and the localization of the photoactive drug in bacteria. In this work we have compared a number of free and apidaecin-conjugated photosensitizers (PSs) differing in structure and charge. Our results indicate that the conjugation of per se ineffective highly hydrophobic PSs to a cationic peptide produces a photosensitizing agent effective against Gram-negative bacteria. Apidaecin cannot improve the phototoxic activity of cationic PSs, which mainly depends on a very high yield of singlet oxygen production in the surroundings of the bacterial outer membrane. Apidaecin-PS conjugates appear most promising for treatment protocols requiring repeated washing after sensitizer delivery.
authors.affiliation: Department of Biology, University of Padova, via U. Bassi 58/B, I-35121 Padova, Italy.
authors.forename: Ryan
authors.initials: R
authors.lastname: Dosselli
authors.forename: Cristiano
authors.initials: C
authors.lastname: Tampieri
authors.forename: Rubén
authors.initials: R
authors.lastname: Ruiz-González
authors.forename: Sonia
authors.initials: S
authors.lastname: De Munari
authors.forename: Xavier
authors.initials: X
authors.lastname: Ragàs
authors.forename: David
authors.initials: D
authors.lastname: Sánchez-García
authors.forename: Montserrat
authors.initials: M
authors.lastname: Agut
authors.forename: Santi
authors.initials: S
authors.lastname: Nonell
authors.forename: Elena
authors.initials: E
authors.lastname: Reddi
authors.forename: Marina
authors.initials: M
authors.lastname: Gobbo
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006090:Gram-Negative Bacteria / Q000187:drug effects; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D055668:Photochemical Processes; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D026082:Singlet Oxygen / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D017319:Photosensitizing Agents; D011166:Porphyrins; C061361:apidaecin; D026082:Singlet Oxygen