Synergistic and antibiofilm properties of ocellatin peptides against multidrug-resistant Pseudomonas aeruginosa

Aim:To test ocellatin peptides (ocellatins-PT2-PT6) for antibacterial and antibiofilm activities and synergy with antibiotics against Pseudomonas aeruginosa. Materials & methods: Normal- and checkerboard-broth microdilution methods were used. Biofilm studies included microtiter plate-based assays and microscopic analysis by confocal laser scanning microscopy and atomic force microscopy. Results: Ocellatins were more active against multidrug-resistant isolates of P. aeruginosa than against susceptible strains. Ocellatin-PT3 showed synergy with ciprofloxacin and ceftazidime against multidrug-resistant isolates and was capable of preventing the proliferation of 48-h mature biofilms at concentrations ranging from 4 to 8× the MIC. Treated biofilms had low viability and were slightly more disaggregated. Conclusion: Ocellatin-PT3 may be promising as a template for the development of novel antimicrobial peptides against P. aeruginosa.This work received financial support from the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia), under the Partnership Agreement PT2020 through project UID/QUI/50006/2013-POCI/01/0145/FEDER/007265 (LAQV/REQUIMTE) and from Programa Operacional Regional do Norte (ON.2 – O Novo Norte),under the Quadro de Referencia Estrat ˆ egico Nacional (QREN) and funded by Fundo Europeu de Desenvolvimento Regional ´ (Feder) through projects: NORTE-01-0145-FEDER-000024, NORTE-01-0145-FEDER-000011 and NORTE-07-0161-FEDER-000111.A Placido is grateful to FCT for financial support through the grant SFRH ´ /BD/97995/2013, POPH-QREN-Tipologia 4.1-Formação Avançada and Fundo Social Europeu and Ministerio da Ciência, Tecnologia e Ensino Superior. The authors have no other relevant ˆ affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.