Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II: Antifungal Activity against Reference Strains and Clinical Isolates of Candida spp.

Aguirre-Guataqui, Katherine; Márquez-Torres, Mateo; Pineda-Castañeda, Héctor Manuel; Vargas-Casanova, Yerly; Ceballos-Garzón, Andrés; Rivera‐Monroy, Zuly Jenny; García‐Castañeda, Javier Eduardo; Parra-Giraldo, Claudia Marcela

doi:10.3390/antibiotics11111561

Cited by 3 publications

(4 citation statements)

References 51 publications

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“…The antifungal activity of the peptide RLLRRLLR, which contains two copies of the buforin minimal antibacterial motif, did not exhibit activity against the C. albicans strain ATCC SC5314 (sensitive to fluconazole) and clinical isolate C. albicans 256 HUSI- PUJ resistant to fluconazole (MIC value of >183 µM) [ 32 ], suggesting that the conjugation of the RLLR sequence with the resorcinarene motif increased the antifungal activity ( Table 2 ). Our results suggest that the binding of the resorcinarene motif to the peptide sequence increased antifungal and antibacterial activity against reference strains and resistant and multiresistant clinical isolates.…”

Section: Resultsmentioning

confidence: 99%

Peptide-Resorcinarene Conjugates Obtained via Click Chemistry: Synthesis and Antimicrobial Activity

et al. 2023

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Antimicrobial resistance (AMR) is one of the top ten threats to public health, as reported by the World Health Organization (WHO). One of the causes of the growing AMR problem is the lack of new therapies and/or treatment agents; consequently, many infectious diseases could become uncontrollable. The need to discover new antimicrobial agents that are alternatives to the existing ones and that allow mitigating this problem has increased, due to the rapid and global expansion of AMR. Within this context, both antimicrobial peptides (AMPs) and cyclic macromolecules, such as resorcinarenes, have been proposed as alternatives to combat AMR. Resorcinarenes present multiple copies of antibacterial compounds in their structure. These conjugate molecules have exhibited antifungal and antibacterial properties and have also been used in anti-inflammatory, antineoplastic, and cardiovascular therapies, as well as being useful in drug and gene delivery systems. In this study, it was proposed to obtain conjugates that contain four copies of AMP sequences over a resorcinarene core. Specifically, obtaining (peptide)4-resorcinarene conjugates derived from LfcinB (20–25): RRWQWR and BF (32–34): RLLR was explored. First, the synthesis routes that allowed obtaining: (a) alkynyl-resorcinarenes and (b) peptides functionalized with the azide group were established. These precursors were used to generate (c) (peptide)4-resorcinarene conjugates by azide-alkyne cycloaddition CuAAC, a kind of click chemistry. Finally, the conjugates’ biological activity was evaluated: antimicrobial activity against reference strains and clinical isolates of bacteria and fungi, and the cytotoxic activity over erythrocytes, fibroblast, MCF-7, and HeLa cell lines. Our results allowed establishing a new synthetic route, based on click chemistry, for obtaining macromolecules derived from resorcinarenes functionalized with peptides. Moreover, it was possible to identify promising antimicrobial chimeric molecules that may lead to advances in the development of new therapeutic agents.

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Section: Resultsmentioning

confidence: 99%

Peptide-Resorcinarene Conjugates Obtained via Click Chemistry: Synthesis and Antimicrobial Activity

et al. 2023

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“…Early preclinical studies have shown that bovine lactoferrin is well tolerated by newborns and retains biological activity in the gut, and that administering bovine lactoferrin to very low birthweight infants protects against late sepsis and necrotizing enterocolitis resulting from various infections [ 58 ]. Moreover, a recent study of the impact of oral administration of lactoferrin saturated with manganese on animal model of neonatal sepsis induced by bacterial translocation showed a significant increase in the Lactobacillus bacterial population, which contributed to the strengthening of the intestinal barrier and inhibition of the phenomenon of translocation [ 59 ]. This fact allows us to assume that the His 6 -OPH/Lfcin combination has the potential to be used as an additive with antimicrobial activity to infant milk formula or baby dairy products, especially considering the fact that His 6 -OPH has been previously successfully applied in vivo as an antidote and its non-toxicity has already been investigated and confirmed [ 38 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Antimicrobial Action of Lactoferrin-Derived Peptides and Quorum Quenching Enzymes

Aslanli

Domnin

Stepanov

et al. 2023

IJMS

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Combined use of various antimicrobial peptides (AMPs) with enzymes that hydrolyze the signaling molecules of the resistance mechanism of various microorganisms, quorum sensing (QS), to obtain effective antimicrobials is one of the leading approaches in solving the antimicrobial resistance problem. Our study investigates the lactoferrin-derived AMPs, lactoferricin (Lfcin), lactoferampin and Lf(1-11), as potential partners for combination with enzymes hydrolyzing lactone-containing QS molecules, the hexahistidine-containing organophosphorus hydrolase (His6-OPH) and penicillin acylase, to obtain effective antimicrobial agents with a scope of practical application. The possibility of the effective combination of selected AMPs and enzymes was first investigated in silico using molecular docking method. Based on the computationally obtained results, His6-OPH/Lfcin combination was selected as the most suitable for further research. The study of physical–chemical characteristics of His6-OPH/Lfcin combination revealed the stabilization of enzymatic activity. A notable increase in the catalytic efficiency of action of His6-OPH in combination with Lfcin in the hydrolysis of paraoxon, N-(3-oxo-dodecanoyl)-homoserine lactone and zearalenone used as substrates was established. Antimicrobial efficiency of His6-OPH/Lfcin combination was determined against various microorganisms (bacteria and yeasts) and its improvement was observed as compared to AMP without enzyme. Thus, our findings demonstrate that His6-OPH/Lfcin combination is a promising antimicrobial agent for practical application.

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“…The designed and synthesized peptides used for the purpose of this study were: C5: RRWQWR-Ahx-KLLKKLLK, C6: KKWQWK-Ahx-RLLRRLLR, and precursor peptides LfcinB (20)(21)(22)(23)(24)(25): RRWQWR, BFII (32)(33)(34)(35) Pal : RLLRRLLR, [K]-LfcinB (20)(21)(22)(23)(24)(25): KKWQWK, and [K]-BFII (32)(33)(34)(35) Pal : KLLKKLLK [18,19]. In both chimeras, 6-aminohexanoic acid (Ahx) was used as the spacer molecule.…”

Section: Antifungal Activity Of Chimeric Peptides Derived From Bovine...mentioning

confidence: 99%

“…Another recently published study tested these chimeras on Candida spp. [ 19 ]. The antifungal effect of these chimeras against C. neoformans has not been reported.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Antifungal Activity of Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II against Cryptococcus neoformans var. grubii

et al. 2022

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Cryptococcosis is associated with high rates of morbidity and mortality. The limited number of antifungal agents, their toxicity, and the difficulty of these molecules in crossing the blood–brain barrier have made the exploration of new therapeutic candidates against Cryptococcus neoformans a priority task. To optimize the antimicrobial functionality and improve the physicochemical properties of AMPs, chemical strategies include combinations of peptide fragments into one. This study aimed to evaluate the binding of the minimum activity motif of bovine lactoferricin (LfcinB) and buforin II (BFII) against C. neoformans var. grubii. The antifungal activity against these chimeras was evaluated against (i) the reference strain H99, (ii) three Colombian clinical strains, and (iii) eleven mutant strains, with the aim of evaluating the possible antifungal target. We found high activity against these strains, with a MIC between 6.25 and 12.5 µg/mL. Studies were carried out to evaluate the effect of the combination of fluconazole treatments, finding a synergistic effect. Finally, when fibroblast cells were treated with 12.5 µg/mL of the chimeras, a viability of more than 65% was found. The results obtained in this study identify these chimeras as potential antifungal molecules for future therapeutic applications against cryptococcosis.

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Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II: Antifungal Activity against Reference Strains and Clinical Isolates of Candida spp.

Cited by 3 publications

References 51 publications

Peptide-Resorcinarene Conjugates Obtained via Click Chemistry: Synthesis and Antimicrobial Activity

Peptide-Resorcinarene Conjugates Obtained via Click Chemistry: Synthesis and Antimicrobial Activity

Synergistic Antimicrobial Action of Lactoferrin-Derived Peptides and Quorum Quenching Enzymes

In Vitro Antifungal Activity of Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II against Cryptococcus neoformans var. grubii

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