The Antimicrobial Peptide Esc(1-21) Synergizes with Colistin in Inhibiting the Growth and in Killing Multidrug Resistant <i>Acinetobacter baumannii</i> Strains

Multidrug-resistant microbial infections and the scarce availability of new antibiotics capable of eradicating them are posing a serious problem to global health security. Among the microorganisms that easily acquire resistance to antibiotics and that are the etiological cause of severe infections,...

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Main Authors: Federica Sacco, Camilla Bitossi, Bruno Casciaro, Maria Rosa Loffredo, Guendalina Fabiano, Luisa Torrini, Flavia Raponi, Giammarco Raponi, Maria Luisa Mangoni
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/11/2/234
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author Federica Sacco
Camilla Bitossi
Bruno Casciaro
Maria Rosa Loffredo
Guendalina Fabiano
Luisa Torrini
Flavia Raponi
Giammarco Raponi
Maria Luisa Mangoni
author_facet Federica Sacco
Camilla Bitossi
Bruno Casciaro
Maria Rosa Loffredo
Guendalina Fabiano
Luisa Torrini
Flavia Raponi
Giammarco Raponi
Maria Luisa Mangoni
author_sort Federica Sacco
collection DOAJ
description Multidrug-resistant microbial infections and the scarce availability of new antibiotics capable of eradicating them are posing a serious problem to global health security. Among the microorganisms that easily acquire resistance to antibiotics and that are the etiological cause of severe infections, there is <i>Acinetobacter baumannii</i>. Carbapenems are the principal agents used to treat <i>A. baumannii</i> infections. However, when strains develop resistance to this class of antibiotics, colistin is considered one of the last-resort drugs. However, the appearance of resistance to colistin also makes treatment of the Acinetobacter infections very difficult. Antimicrobial peptides (AMP) from the innate immunity hold promise as new alternative antibiotics due to their multiple biological properties. In this study, we characterized the activity and the membrane-perturbing mechanism of bactericidal action of a derivative of a frog-skin AMP, namely Esc(1-21), when used alone or in combination with colistin against multidrug-resistant <i>A. baumannii</i> clinical isolates. We found that the mixture of the two compounds had a synergistic effect in inhibiting the growth and killing of all of the tested strains. When combined at dosages below the minimal inhibitory concentration, the two drugs were also able to slow down the microbial growth and to potentiate the membrane-perturbing effect. To the best of our knowledge, this is the first report showing a synergistic effect between AMPs, i.e., Esc(1-21), and colistin against colistin-resistant <i>A. baumannii</i> clinical isolates, highlighting the potential clinical application of such combinational therapy.
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spelling doaj.art-1994bd4acbcc46dda971fa679995967e2023-11-23T18:28:42ZengMDPI AGAntibiotics2079-63822022-02-0111223410.3390/antibiotics11020234The Antimicrobial Peptide Esc(1-21) Synergizes with Colistin in Inhibiting the Growth and in Killing Multidrug Resistant <i>Acinetobacter baumannii</i> StrainsFederica Sacco0Camilla Bitossi1Bruno Casciaro2Maria Rosa Loffredo3Guendalina Fabiano4Luisa Torrini5Flavia Raponi6Giammarco Raponi7Maria Luisa Mangoni8Department of Molecular Medicine, University of Rome “La Sapienza”, 00161 Rome, ItalyDepartment of Molecular Medicine, University of Rome “La Sapienza”, 00161 Rome, ItalyDepartment of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyClinical Microbiology Laboratory, Sapienza University Hospital Policlinico Umberto I of Rome, 00161 Rome, ItalyClinical Microbiology Laboratory, Sapienza University Hospital Policlinico Umberto I of Rome, 00161 Rome, ItalyDepartment of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyMultidrug-resistant microbial infections and the scarce availability of new antibiotics capable of eradicating them are posing a serious problem to global health security. Among the microorganisms that easily acquire resistance to antibiotics and that are the etiological cause of severe infections, there is <i>Acinetobacter baumannii</i>. Carbapenems are the principal agents used to treat <i>A. baumannii</i> infections. However, when strains develop resistance to this class of antibiotics, colistin is considered one of the last-resort drugs. However, the appearance of resistance to colistin also makes treatment of the Acinetobacter infections very difficult. Antimicrobial peptides (AMP) from the innate immunity hold promise as new alternative antibiotics due to their multiple biological properties. In this study, we characterized the activity and the membrane-perturbing mechanism of bactericidal action of a derivative of a frog-skin AMP, namely Esc(1-21), when used alone or in combination with colistin against multidrug-resistant <i>A. baumannii</i> clinical isolates. We found that the mixture of the two compounds had a synergistic effect in inhibiting the growth and killing of all of the tested strains. When combined at dosages below the minimal inhibitory concentration, the two drugs were also able to slow down the microbial growth and to potentiate the membrane-perturbing effect. To the best of our knowledge, this is the first report showing a synergistic effect between AMPs, i.e., Esc(1-21), and colistin against colistin-resistant <i>A. baumannii</i> clinical isolates, highlighting the potential clinical application of such combinational therapy.https://www.mdpi.com/2079-6382/11/2/234antibiotic resistance<i>Acinetobacter baumannii</i>antimicrobial peptidescolistinsynergymembrane perturbation
spellingShingle Federica Sacco
Camilla Bitossi
Bruno Casciaro
Maria Rosa Loffredo
Guendalina Fabiano
Luisa Torrini
Flavia Raponi
Giammarco Raponi
Maria Luisa Mangoni
The Antimicrobial Peptide Esc(1-21) Synergizes with Colistin in Inhibiting the Growth and in Killing Multidrug Resistant <i>Acinetobacter baumannii</i> Strains
Antibiotics
antibiotic resistance
<i>Acinetobacter baumannii</i>
antimicrobial peptides
colistin
synergy
membrane perturbation
title The Antimicrobial Peptide Esc(1-21) Synergizes with Colistin in Inhibiting the Growth and in Killing Multidrug Resistant <i>Acinetobacter baumannii</i> Strains
title_full The Antimicrobial Peptide Esc(1-21) Synergizes with Colistin in Inhibiting the Growth and in Killing Multidrug Resistant <i>Acinetobacter baumannii</i> Strains
title_fullStr The Antimicrobial Peptide Esc(1-21) Synergizes with Colistin in Inhibiting the Growth and in Killing Multidrug Resistant <i>Acinetobacter baumannii</i> Strains
title_full_unstemmed The Antimicrobial Peptide Esc(1-21) Synergizes with Colistin in Inhibiting the Growth and in Killing Multidrug Resistant <i>Acinetobacter baumannii</i> Strains
title_short The Antimicrobial Peptide Esc(1-21) Synergizes with Colistin in Inhibiting the Growth and in Killing Multidrug Resistant <i>Acinetobacter baumannii</i> Strains
title_sort antimicrobial peptide esc 1 21 synergizes with colistin in inhibiting the growth and in killing multidrug resistant i acinetobacter baumannii i strains
topic antibiotic resistance
<i>Acinetobacter baumannii</i>
antimicrobial peptides
colistin
synergy
membrane perturbation
url https://www.mdpi.com/2079-6382/11/2/234
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