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

Federica Sacco,Camilla Bitossi,Bruno Casciaro,Maria Luisa Mangoni,Giammarco Raponi,Flavia Raponi,Maria Rosa Loffredo,Luisa Torrini,Guendalina Fabiano

doi:10.3390/antibiotics11020234

Abstract

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 Acinetobacter baumannii. Carbapenems are the principal agents used to treat A. baumannii 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 A. baumannii 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 A. baumannii clinical isolates, highlighting the potential clinical application of such combinational therapy.

Highlights

Infections sustained by multi-drug-resistant bacteria (MDR), i.e., bacteria resistant to at least three different classes of antimicrobial agents, represent a serious threat for human health
Geneencoded antimicrobial peptides (AMPs) of the innate immunity are attractive candidates for alternative anti-infective compounds. These are short-length and low molecular weight molecules with interesting properties such as (i) broad spectrum of antimicrobial activity; (ii) membrane-perturbing effect as a primary mechanism of antibacterial action that confers cell selectivity limiting the induction of resistance; (iii) capability to modulate the host immune response and to promote wound-healing; and (iv) ability to synergize with other Antimicrobial peptides (AMP) or conventional antibiotics [20,21,22,23,24]
With the aim to re-evaluate the efficacy of colistin, we investigated whether the usage of this drug in combination with Esc(1-21) had a synergistic effect in inhibiting the growth and/or in killing colistin-resistant clinical A. baumannii strains along with the underlying molecular mechanism

Summary

Introduction

Infections sustained by multi-drug-resistant bacteria (MDR), i.e., bacteria resistant to at least three different classes of antimicrobial agents, represent a serious threat for human health. Geneencoded antimicrobial peptides (AMPs) of the innate immunity are attractive candidates for alternative anti-infective compounds These are short-length and low molecular weight molecules with interesting properties such as (i) broad spectrum of antimicrobial activity; (ii) membrane-perturbing effect as a primary mechanism of antibacterial action that confers cell selectivity limiting the induction of resistance; (iii) capability to modulate the host immune response and to promote wound-healing; and (iv) ability to synergize with other AMPs or conventional antibiotics [20,21,22,23,24]. With the aim to re-evaluate the efficacy of colistin, we investigated whether the usage of this drug in combination with Esc(1-21) had a synergistic effect in inhibiting the growth and/or in killing colistin-resistant clinical A. baumannii strains along with the underlying molecular mechanism

Methods

Results

Conclusion