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Peptide-Based Antibiotics: Challenges and Opportunities

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antimicrobial Peptides".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 30229

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Prof. Dr. Paul Robert Hansen

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Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
Interests: antimicrobial peptides; drug delivery
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Prof. Dr. Henrik Franzyk

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Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
Interests: antimicrobial peptides; immunomodulation; drug delivery
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Dear Colleagues,

Antimicrobial resistance is one of the most imminent threats to public health. There is a critical unmet need for novel antibiotics capable of killing multidrug-resistant bacteria. AMPs are a part of the innate immune system of all living organisms and typically exhibit broad-spectrum activity against Gram-positive and Gram-negative bacteria. Furthermore, AMPs display a wide range of immunomodulatory properties. Compared to traditional antibiotics, AMPs appear to have a lower propensity to select for resistant strains. However, natural AMPs are potentially toxic and rapidly degraded by proteases with an ensuing low bioavailability. The stability of AMPs can typically be improved by chemical modification such as lipidation, cyclization, or the insertion of non-standard building blocks, including D-amino acids or peptoids. Alternatively, peptidomimetics (i.e., oligomers with a backbone that is not entirely based on α-amino acid residues) such as α-peptide/β-peptides, α-peptides/α-peptoids, or α-peptide/β-peptoids are very promising. Other interesting approaches are peptoids, AMP dendrimers, peptide–antibiotic conjugates, and peptidomimetics for the repurposing of antibiotics against multidrug-resistant pathogens.

Although the field of peptide-based antibiotics has developed tremendously over the last two decades (e.g., by improved design, mechanistic understanding, formulation, and delivery), therapeutic breakthroughs for the systemic treatment of bacterial infections remain to be achieved.

For this Special Issue entitled ”Peptide-Based Antibiotics: Challenges and Opportunities”, we invite authors to submit articles covering all aspects of this theme.

Prof. Paul Robert Hansen
Prof. Dr. Henrik Franzyk
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

antimicrobial peptides
drug delivery

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Published Papers (11 papers)

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Research

20 pages, 2910 KiB

Open AccessArticle

Synergy between Human Peptide LL-37 and Polymyxin B against Planktonic and Biofilm Cells of Escherichia coli and Pseudomonas aeruginosa

by Kylen E. Ridyard, Mariam Elsawy, Destina Mattrasingh, Darien Klein, Janine Strehmel, Carole Beaulieu, Alex Wong and Joerg Overhage

Antibiotics 2023, 12(2), 389; https://doi.org/10.3390/antibiotics12020389 - 15 Feb 2023

Cited by 12 | Viewed by 3221

Abstract

The rise in antimicrobial resistant bacteria is limiting the number of effective treatments for bacterial infections. Escherichia coli and Pseudomonas aeruginosa are two of the pathogens with the highest prevalence of resistance, and with the greatest need for new antimicrobial agents. Combinations of antimicrobial peptides (AMPs) and antibiotics that display synergistic effects have been shown to be an effective strategy in the development of novel therapeutic agents. In this study, we investigated the synergy between the AMP LL-37 and various classes of antibiotics against E. coli and P. aeruginosa strains. Of the six antibiotics tested (ampicillin, tetracycline, ciprofloxacin, gentamicin, aztreonam, and polymyxin B (PMB)), LL-37 displayed the strongest synergy against E. coli MG1655 and P. aeruginosa PAO1 laboratory strains when combined with PMB. Given the strong synergy, the PMB + LL-37 combination was chosen for further examination where it demonstrated synergy against multidrug-resistant and clinical E. coli isolates. Synergy of PMB + LL-37 towards clinical isolates of P. aeruginosa varied and showed synergistic, additive, or indifferent effects. The PMB + LL-37 combination treatment showed significant prevention of biofilm formation as well as eradication of pre-grown E. coli and P. aeruginosa biofilms. Using the Galleria mellonella wax worm model, we showed that the PMB + LL-37 combination treatment retained its antibacterial capacities in vivo. Flow analyses were performed to characterize the mode of action. The results of the present study provide proof of principle for the synergistic response between LL-37 and PMB and give novel insights into a promising new antimicrobial combination against gram-negative planktonic and biofilm cells. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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9 pages, 1200 KiB

Open AccessArticle

Structure–Activity Relationship Studies of Substitutions of Cationic Amino Acid Residues on Antimicrobial Peptides

by Mayu Takada, Takahito Ito, Megumi Kurashima, Natsumi Matsunaga, Yosuke Demizu and Takashi Misawa

Antibiotics 2023, 12(1), 19; https://doi.org/10.3390/antibiotics12010019 - 23 Dec 2022

Cited by 8 | Viewed by 2170

Abstract

Antimicrobial peptides (AMPs) have received considerable attention as next-generation drugs for infectious diseases. Amphipathicity and the formation of a stabilized secondary structure are required to exert their antimicrobial activity by insertion into the microbial membrane, resulting in lysis of the bacteria. We previously reported the development of a novel antimicrobial peptide, 17KKV, based on the Magainin 2 sequence. The peptide was obtained by increasing the amphipathicity due to the replacement of amino acid residues. Moreover, we studied the structural development of 17KKV and revealed that the secondary structural control of 17KKV by the introduction of non-proteinogenic amino acids such as α,α-disubstituted amino acids or side-chain stapling enhanced its antimicrobial activity. Among them, peptide 1, which contains 2-aminobutyric acid residues in the 17KKV sequence, showed potent antimicrobial activity against multidrug-resistant Pseudomonus aeruginosa (MDRP) without significant hemolytic activity against human red blood cells. However, the effects of cationic amino acid substitutions on secondary structures and antimicrobial activity remain unclear. In this study, we designed and synthesized a series of peptide 1 by the replacement of Lys residues with several types of cationic amino acids and evaluated their secondary structures, antimicrobial activity, hemolytic activity, and resistance against digestive enzymes. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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16 pages, 1786 KiB

Open AccessFeature PaperArticle

Associating Biological Activity and Predicted Structure of Antimicrobial Peptides from Amphibians and Insects

by Amelia Richter, Darcy Sutherland, Hossein Ebrahimikondori, Alana Babcock, Nathan Louie, Chenkai Li, Lauren Coombe, Diana Lin, René L. Warren, Anat Yanai, Monica Kotkoff, Caren C. Helbing, Fraser Hof, Linda M. N. Hoang and Inanc Birol

Antibiotics 2022, 11(12), 1710; https://doi.org/10.3390/antibiotics11121710 - 27 Nov 2022

Cited by 5 | Viewed by 3194

Abstract

Antimicrobial peptides (AMPs) are a diverse class of short, often cationic biological molecules that present promising opportunities in the development of new therapeutics to combat antimicrobial resistance. Newly developed in silico methods offer the ability to rapidly discover numerous novel AMPs with a variety of physiochemical properties. Herein, using the rAMPage AMP discovery pipeline, we bioinformatically identified 51 AMP candidates from amphibia and insect RNA-seq data and present their in-depth characterization. The studied AMPs demonstrate activity against a panel of bacterial pathogens and have undetected or low toxicity to red blood cells and human cultured cells. Amino acid sequence analysis revealed that 30 of these bioactive peptides belong to either the Brevinin-1, Brevinin-2, Nigrocin-2, or Apidaecin AMP families. Prediction of three-dimensional structures using ColabFold indicated an association between peptides predicted to adopt a helical structure and broad-spectrum antibacterial activity against the Gram-negative and Gram-positive species tested in our panel. These findings highlight the utility of associating the diverse sequences of novel AMPs with their estimated peptide structures in categorizing AMPs and predicting their antimicrobial activity. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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18 pages, 2799 KiB

Open AccessArticle

Bioengineered Nisin A Derivatives Display Enhanced Activity against Clinical Neonatal Pathogens

by Anna Desmond, Fiona O’Halloran, Lesley Cotter, Colin Hill and Des Field

Antibiotics 2022, 11(11), 1516; https://doi.org/10.3390/antibiotics11111516 - 30 Oct 2022

Cited by 5 | Viewed by 1963

Abstract

Neonatal infection is a significant cause of mortality and morbidity in infants. The global incidence of multi-drug resistance continues to rise among neonatal pathogens, indicating a need for alternative treatment strategies. Nisin is an antimicrobial peptide that exhibits broad-spectrum activity against a wide variety of clinical pathogens and can be used in combination with antibiotics to improve their effectiveness. This study examined the activity of nisin and bioengineered derivatives against multi-drug resistant Streptococcus agalactiae and Staphylococcus capitis isolates and investigated the potential synergy between nisin peptides and selected antibiotics. Whole genome sequence analysis of the strains revealed the presence of multi-drug resistant determinants, e.g., macrolide, tetracycline, β-lactam, aminoglycoside, while the S. agalactiae strains all possessed both nsr and nsrFP genes and the S. capitis strains were found to encode the nsr gene alone. Deferred antagonism assays demonstrated that nisin PV had improved antimicrobial activity against all strains tested (n = 10). The enhanced specific activity of this peptide was confirmed using minimum inhibitory concentrations (MIC) (0–4-fold lower MIC for nisin PV) and broth-based survival assays. Combinations of nisin peptides with antibiotics were assessed for enhanced antimicrobial activity using growth and time-kill assays and revealed a more effective nisin PV/ampicillin combination against one S. capitis strain while a nisin A/erythromycin combination displayed a synergistic effect against one S. agalactiae strain. The findings of this study suggest that nisin derivatives alone and in combination with antibiotics have potential as alternative antimicrobial strategies to target neonatal pathogens. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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20 pages, 22788 KiB

Open AccessArticle

Histidine 19 Residue Is Essential for Cell Internalization of Antifungal Peptide SmAP_α1-21 Derived from the α-Core of the Silybum marianum Defensin DefSm2-D in Fusarium graminearum

by Agustina Fernández, Mariano González, Ismael Malbrán, Romina F. Vázquez, Sabina M. Maté, Fanny Guzmán, Laura S. Bakás and Sandra Vairo Cavalli

Antibiotics 2022, 11(11), 1501; https://doi.org/10.3390/antibiotics11111501 - 28 Oct 2022

Viewed by 1991

Abstract

The synthetic peptide SmAP_α1-21 (KLCEKPSKTWFGNCGNPRHCG) derived from DefSm2-D defensin α-core is active at micromolar concentrations against the phytopathogenic fungus Fusarium graminearum and has a multistep mechanism of action that includes alteration of the fungal cell wall and membrane permeabilization. Here, we continued the study of this peptide’s mode of action and explored the correlation between the biological activity and its primary structure. Transmission electron microscopy was used to study the ultrastructural effects of SmAP_α1-21 in conidial cells. New peptides were designed by modifying the parent peptide SmAP_α1-21 (SmAPH19R and SmAPH19A, where His19 was replaced by Arg or Ala, respectively) and synthesized by the Fmoc solid phase method. Antifungal activity was determined against F. graminearum. Membrane permeability and subcellular localization in conidia were studied by confocal laser scanning microscopy (CLSM). Reactive oxygen species (ROS) production was assessed by fluorescence spectroscopy and CLSM. SmAP_α1-21 induced peroxisome biogenesis and oxidative stress through ROS production in F. graminearum and was internalized into the conidial cells’ cytoplasm. SmAPH19R and SmAPH19A were active against F. graminearum with minimal inhibitory concentrations (MICs) of 38 and 100 µM for SmAPH19R and SmAPH19A, respectively. The replacement of His19 by Ala produced a decrease in the net charge with a significant increase in the MIC, thus evidencing the importance of the positive charge in position 19 of the antifungal peptide. Like SmAP_α1-21, SmAP2H19A and SmAP2H19R produced the permeabilization of the conidia membrane and induced oxidative stress through ROS production. However, SmAPH19R and SmAPH19A were localized in the conidia cell wall. The replacement of His19 by Ala turned all the processes slower. The extracellular localization of peptides SmAPH19R and SmAPH19A highlights the role of the His19 residue in the internalization. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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10 pages, 818 KiB

Open AccessArticle

C-Locked Analogs of the Antimicrobial Peptide BP214

by Ida Kristine Lysgaard Andersen, Thomas T. Thomsen, Jasmina Rashid, Thomas Rønnemoes Bobak, Alberto Oddo, Henrik Franzyk, Anders Løbner-Olesen and Paul R. Hansen

Antibiotics 2022, 11(8), 1080; https://doi.org/10.3390/antibiotics11081080 - 9 Aug 2022

Cited by 4 | Viewed by 2327

Abstract

BP214 is an all-D antimicrobial peptide amide, kklfkkilryl, which shows an excellent activity against colistin-resistant Acinetobacter baumannii and a low hemolytic activity. The aim of the present work was to investigate how C-terminus-to-side chain macrocyclization and fatty acid modification affect the antimicrobial and hemolytic activity of this peptide. In total, 18 analogs of BP214 were synthesized using a combination of Fmoc-based solid-phase peptide synthesis and the submonomer approach. Cyclization was achieved by reacting the ε-amino group of a C-terminal lysine residue with a bromoacetylgroup attached to the N^α amino group of the N-terminal amino acid, generating a secondary amine at which the exocyclic lipopeptide tail was assembled. Three different ring sizes (i.e., 3–5 amino acid residues) of C-locked analogs combined with fatty acids of different lengths (i.e., C₁₀–C₁₄) were investigated. The antimicrobial activity of the analogs was tested against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The most promising compound was analog 13 (MIC = 4 µg/mL (2.4 µM) against E. coli and 36% hemolysis of red blood cells at 150 µM). In a time-kill assay, this peptide showed a significant, concentration-dependent reduction in viable E. coli cells comparable to that seen for colistin. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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31 pages, 4473 KiB

Open AccessArticle

Short Tryptamine-Based Peptoids as Potential Therapeutics for Microbial Keratitis: Structure-Function Correlation Studies

by Ghayah Bahatheg, Rajesh Kuppusamy, Muhammad Yasir, David StC. Black, Mark Willcox and Naresh Kumar

Antibiotics 2022, 11(8), 1074; https://doi.org/10.3390/antibiotics11081074 - 8 Aug 2022

Cited by 6 | Viewed by 2318

Abstract

Peptoids are peptidomimetics that have attracted considerable interest as a promising class of antimicrobials against multi-drug-resistant bacteria due to their resistance to proteolysis, bioavailability, and thermal stability compared to their corresponding peptides. Staphylococcus aureus is a significant contributor to infections worldwide and is a major pathogen in ocular infections (keratitis). S. aureus infections can be challenging to control and treat due to the development of multiple antibiotic resistance. This work describes short cationic peptoids with activity against S. aureus strains from keratitis. The peptoids were synthesized via acid amine-coupling between naphthyl-indole amine or naphthyl-phenyl amine with different amino acids to produce primary amines (series I), mono-guanidines (series II), tertiary amine salts (series III), quaternary ammonium salts (series IV), and di-guanidine (series V) peptoids. The antimicrobial activity of the peptoids was compared with ciprofloxacin, an antibiotic that is commonly used to treat keratitis. All new compounds were active against Staphylococcus aureus S.aureus 38. The most active compounds against S.aur38 were 20a and 22 with MIC = 3.9 μg mL⁻¹ and 5.5 μg mL⁻¹, respectively. The potency of these two active molecules was investigated against 12 S. aureus strains that were isolated from microbial keratitis. Compounds 20a and 22 were active against 12 strains with MIC = 3.2 μg mL⁻¹ and 2.1 μg mL⁻¹, respectively. There were two strains that were resistant to ciprofloxacin (Sa.111 and Sa.112) with MIC = 128 μg mL⁻¹ and 256 μg mL⁻¹, respectively. Compounds 12c and 13c were the most active against E. coli, with MIC > 12 μg mL⁻¹. Cytoplasmic membrane permeability studies suggested that depolarization and disruption of the bacterial cell membrane could be a possible mechanism for antibacterial activity and the hemolysis studies toward horse red blood cells showed that the potent compounds are non-toxic at up to 50 μg mL⁻¹. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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15 pages, 689 KiB

Open AccessArticle

Genomewide Analysis and Biological Characterization of Cathelicidins with Potent Antimicrobial Activity and Low Cytotoxicity from Three Bat Species

by Munjeong Choi, Hye-sun Cho, Byeongyong Ahn, Somasundaram Prathap, Soundrarajan Nagasundarapandian and Chankyu Park

Antibiotics 2022, 11(8), 989; https://doi.org/10.3390/antibiotics11080989 - 22 Jul 2022

Cited by 3 | Viewed by 2127

Abstract

Cathelicidins are potent antimicrobial peptides with broad spectrum antimicrobial activity in many vertebrates and an important component of the innate immune system. However, our understanding of the genetic variations and biological characteristics of bat cathelicidins is limited. In this study, we performed genome-level analysis of the antimicrobial peptide cathelicidins from seven bat species in the six families, listed 19 cathelicidin-like sequences, and showed that the number of functional cathelicidin genes differed among bat species. Based on the identified biochemical characteristics of bat cathelicidins, three cathelicidins, HA-CATH (from Hipposideros armiger), ML-CATH (from Myotis lucifugus), and PD-CATH (from Phyllostomus discolor), with clear antimicrobial signatures were chemically synthesized and evaluated antimicrobial activity. HA-CATH showed narrow-spectrum antibacterial activity against a panel of 12 reference bacteria, comprising 6 Gram-negative and 6 Gram-positive strains. However, ML-CATH and PD-CATH showed potent antibacterial activity against a broad spectrum of Gram-negative and Gram-positive bacteria with minimum inhibitory concentration (MIC) of 1 and 3 μg/mL, respectively, against Staphylococcus aureus. ML-CATH and PD-CATH also showed antifungal activities against Candida albicans and Cryptococcus cuniculi with MIC of 5 to 40 μg/mL, respectively, and 80% inhibition of the metabolism of Mucor hiemalis hyphae at 80 μg/mL, while displaying minimal cytotoxicity to HaCaT cells. Taken together, although the spectrum and efficacy of bat cathelicidins were species-dependent, the antimicrobial activity of ML-CATH and PD-CATH was comparable to that of other highly active cathelicidins in vertebrates while having negligible cytotoxicity to mammalian cells. ML-CATH and PD-CATH can be exploited as promising candidates for the development of antimicrobial therapeutics. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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16 pages, 3187 KiB

Open AccessArticle

Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of Infection

by Hannah E. Caraway, Jonathan Z. Lau, Bar Maron, Myung Whan Oh, Yael Belo, Aya Brill, Einav Malach, Nahed Ismail, Zvi Hayouka and Gee W. Lau

Antibiotics 2022, 11(3), 413; https://doi.org/10.3390/antibiotics11030413 - 19 Mar 2022

Cited by 11 | Viewed by 3636

Abstract

Antibiotic resistance is one of the greatest crises in human medicine. Increased incidents of antibiotic resistance are linked to clinical overuse and overreliance on antibiotics. Among the ESKAPE pathogens, Acinetobacter baumannii, especially carbapenem-resistant isolates, has emerged as a significant threat in the context of blood, urinary tract, lung, and wound infections. Therefore, new approaches that limit the emergence of antibiotic resistant A. baumannii are urgently needed. Recently, we have shown that random peptide mixtures (RPMs) are an attractive alternative class of drugs to antibiotics with strong safety and pharmacokinetic profiles. RPMs are antimicrobial peptide mixtures produced by incorporating two amino acids at each coupling step, rendering them extremely diverse but still defined in their overall composition, chain length, and stereochemistry. The extreme diversity of RPMs may prevent bacteria from evolving resistance rapidly. Here, we demonstrated that RPMs rapidly and efficiently kill different strains of A. baumannii, inhibit biofilm formation, and disrupt mature biofilms. Importantly, RPMs attenuated bacterial burden in mouse models of acute pneumonia and soft tissue infection and significantly reduced mouse mortality during sepsis. Collectively, our results demonstrate RPMs have the potential to be used as powerful therapeutics against antibiotic-resistant A. baumannii. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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14 pages, 1968 KiB

Open AccessArticle

Effects of Lysine N-ζ-Methylation in Ultrashort Tetrabasic Lipopeptides (UTBLPs) on the Potentiation of Rifampicin, Novobiocin, and Niclosamide in Gram-Negative Bacteria

by Linus Schweizer, Danyel Ramirez and Frank Schweizer

Antibiotics 2022, 11(3), 335; https://doi.org/10.3390/antibiotics11030335 - 3 Mar 2022

Cited by 9 | Viewed by 2802

Abstract

Outer membrane (OM) drug impermeability typically associated with a molecular weight above 600 Da and high hydrophobicity prevents accumulation of many antibiotics in Gram-negative bacteria (GNB). Previous studies have shown that ultrashort tetrabasic lipopeptides (UTBLPs) containing multiple lysine residues potentiate Gram-positive bacteria (GPB)-selective antibiotics in GNB by enhancing OM permeability. However, there is no available information on how N-substitution at the ζ-position of lysine in UTBLPs affects antibiotic potentiation in GNB. To study these effects, we prepared a series of branched and linear UTBLPs that differ in the degree of N-ζ-methylation and studied their potentiating effects with GPB-selective antibiotics including rifampicin, novobiocin, niclosamide, and chloramphenicol against wild-type and multidrug-resistant GNB isolates. Our results show that increasing N-ζ-methylation reduces or abolishes the potentiating effects of UTBLPs with rifampicin, novobiocin, and niclosamide against GNB. No trend was observed with chloramphenicol that is largely affected by efflux. We were unable to observe a correlation between the strength of the antibiotic potentiating effect to the increase in fluorescence in the 1-N-phenylnaphthylamine (NPN) OM permeability assay suggesting that other factors besides OM permeability of NPN play a role in antibiotic potentiation. In conclusion, our study has elucidated crucial structure–activity relationships for the optimization of polybasic antibiotic potentiators in GNB. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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12 pages, 2409 KiB

Open AccessArticle

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

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

Antibiotics 2022, 11(2), 234; https://doi.org/10.3390/antibiotics11020234 - 11 Feb 2022

Cited by 13 | Viewed by 2463

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. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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