In vitro activity of Protegrin-1, alone and in combination with clinically useful antibiotics, against Acinetobacter baumannii strains isolated from surgical wounds

Gianluca Morroni , Oriana Simonetti , Andrea Brenciani , Lucia Brescini , Wojciech Kamysz , Elżbieta Kamysz , Damian Neubauer , Miriam Caffarini , Monia Orciani , Eleonora Giovanetti , Annamaria Offidani , Andrea Giacometti , Oscar Cirioni

Abstract

In the past few years the increasing incidence of hospital infections with Acinetobacter baumannii, especially in immunocompromised patients, and its proneness to develop multidrug resistance have been raising considerable concern. This study examines the antimicrobial and antibiofilm activity of protegrin 1 (PG-1), an antimicrobial peptide from porcine leukocytes, against A. baumannii strains isolated from surgical wounds. PG-1 was tested both alone and combined with the antibiotics commonly used in clinical settings. Its antimicrobial activity was evaluated by determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), checkerboard assays, and time-kill experiments. Its effects on biofilm inhibition/eradication were tested with crystal violet staining. The strains were grown in subinhibitory or increasing PG-1 concentrations to test the development of resistance. Mammalian cell toxicity was tested by XTT assays. PG-1 MICs and MBCs ranged from 2 to 8 µg/ml. PG-1 was most active and demonstrated a synergistic interaction with colistin, a last resort antibiotic. Interestingly, antagonism was never observed. In time-kill experiments, incubation with 2 × MIC for 30 min suppressed all viable cells. PG-1 did not select resistant strains and showed a limited effect on cell viability, but it did exert a strong activity against multidrug-resistant A. baumannii. In contrast, in our experimental conditions it had no effect on biofilm inhibition/eradication. PG-1 thus seems to be a promising antimicrobial agent against multidrug-resistant Gram-negative infections.
Author Gianluca Morroni
Gianluca Morroni,,
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, Oriana Simonetti
Oriana Simonetti,,
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, Andrea Brenciani
Andrea Brenciani,,
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, Lucia Brescini
Lucia Brescini,,
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, Wojciech Kamysz
Wojciech Kamysz,,
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, Elżbieta Kamysz (FCh / DMBt / LChBM)
Elżbieta Kamysz,,
- Laboratory of Chemistry of Biological Macromolecules
, Damian Neubauer
Damian Neubauer,,
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, Miriam Caffarini
Miriam Caffarini,,
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, Monia Orciani
Monia Orciani,,
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, Eleonora Giovanetti
Eleonora Giovanetti,,
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et al.`
Journal seriesMedical Microbiology and Immunology, ISSN 0300-8584, e-ISSN 1432-1831, (N/A 100 pkt)
Issue year2019
Vol208
No6
Pages877-883
Publication size in sheets0.5
Keywords in EnglishAcinetobacter baumannii, antimicrobial peptides, Protegrin-1, synergy, checkerboard assay
ASJC Classification2700 General Medicine; 2723 Immunology and Allergy; 2726 Microbiology (medical); 2403 Immunology
DOIDOI:10.1007/s00430-019-00624-7
URL https://doi.org/10.1007/s00430-019-00624-7
Languageen angielski
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Morroni_Gianluca_In_Vitro_Activity_Of_Protegrin_1_2019.pdf 843.06 KB
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 28-01-2020, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.733; WoS Impact Factor: 2018 = 2.96 (2) - 2018=2.837 (5)
Citation count*2 (2020-03-18)
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