Investigations into the membrane activity of arenicin antimicrobial peptide AA139

Edwards, David; Henriques, Sónia Troeira; Blaskovich, Mark A.T.; Elliott, Alysha G.; Cooper, Matthew A.

doi:10.1016/j.bbagen.2022.130156

Cited by 7 publications

(7 citation statements)

References 61 publications

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“…Their high selectivity makes these peptides promising prototypes of new antibiotics. In particular, comprehensive preclinical studies are being conducted with AA139 peptide, which has shown good effectiveness against Gram-negative bacteria including antibiotic-resistant strains both in vitro and in animal models [ 25 , 26 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…For equal hemolytic activity toward human erythrocytes, an order of magnitude higher concentration of AA139 was required compared with Ar-3. However, in terms of antimicrobial activity, AA139 was several times more effective than Ar-3 [ 25 , 26 ]. Such differences in the activity pattern can be explained by the greater selectivity of AA139 to highly negatively-charged membranes characteristic of bacterial cells [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, in terms of antimicrobial activity, AA139 was several times more effective than Ar-3 [ 25 , 26 ]. Such differences in the activity pattern can be explained by the greater selectivity of AA139 to highly negatively-charged membranes characteristic of bacterial cells [ 26 ]. The AA139 peptide is also highly resistant to the inhibitory action of blood serum, in contrast to Ar-3 [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Modulation of Complement Activation by Therapeutically Prospective Analogues of the Marine Polychaeta Arenicin Peptides

et al. 2022

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The widespread resistance to antibiotics in pathogenic bacteria makes the development of a new generation of antimicrobials an urgent task. The development of new antibiotics must be accompanied by a comprehensive study of all of their biological activities in order to avoid adverse side-effects from their application. Some promising antibiotic prototypes derived from the structures of arenicins, antimicrobial peptides from the lugworm Arenicola marina, have been developed. Previously, we described the ability of natural arenicins -1 and -2 to modulate the human complement system activation in vitro. In this regard, it seems important to evaluate the effect of therapeutically promising arenicin analogues on complement activation. Here, we describe the complement-modulating activity of three such analogues, Ar-1[V8R], ALP1, and AA139. We found that the mode of action of Ar-1[V8R] and ALP1 on the complement was similar to that of natural arenicins, which can both activate and inhibit the complement, depending on the concentration. However, Ar-1[V8R] behaved predominantly as an inhibitor, showing only a moderate increase in C3a production in the alternative pathway model and no enhancement at all of the classical pathway of complement activation. In contrast, the action of ALP1 was characterized by a marked increase in the complement activation through the classical pathway in the concentration range of 2.5–20 μg/mL. At the same time, at higher concentrations (80–160 μg/mL), this peptide exhibited a complement inhibitory effect characteristic of the other arenicins. Peptide AA139, like other arenicins, exhibited an inhibitory effect on complement at a concentration of 160 μg/mL, but was much less pronounced. Overall, our results suggest that the effect on the complement system should be taken into account in the development of antibiotics based on arenicins.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Vitro Modulation of Complement Activation by Therapeutically Prospective Analogues of the Marine Polychaeta Arenicin Peptides

et al. 2022

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“…They observed an increased activity of AA139 in the plasmatic membrane permeability, in agreement with its improved antibacterial potency. [93] Additionally, fluorescence microscopy of single live bacterial cells can provide detailed information about membrane permeabilization, allowing dissection between OM and IM permeabilization. [94] In a study conducted by Rangarajan et al, they evaluated the interaction of the AMP cecropin A with single E. coli cells in real time with subsecond resolution.…”

Section: In Vivo Assessment Of Amp-induced Permeabilitymentioning

confidence: 99%

“…They observed an increased activity of AA139 in the plasmatic membrane permeability, in agreement with its improved antibacterial potency. [ 93 ]…”

Section: In Vivo Assessment Of Amp‐induced Permeabilitymentioning

confidence: 99%

Membrane permeability and antimicrobial peptides: Much more than just making a hole

et al. 2023

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Antimicrobial peptides (AMPs) are one of the elements of innate immunity that have a crucial role in fighting infections. These molecules are produced by all kinds of cells and can display a wide spectrum of action against bacterial or fungal infections. Bacterial resistance toward broad‐spectrum antibiotics has become a major concern in recent years. In this context, AMPs have emerged as promising alternative therapy in response to this increasing problem because of their ability to inhibit growth and biofilm formation, even in drug‐resistant microorganisms. However, despite the myriad of patents filed related to AMPs, only a small proportion of AMPs have already received certification, either by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). In order to pave the way of AMPs to certification, a comprehensive knowledge of the mechanism of action of these peptides is essential. Several models have been proposed to explain it and the permeabilization of the bacterial envelope seems to play a key role in most of them. In this review, we describe the different techniques that are generally used to assess the permeabilization induced by AMPs in either in vivo or in vitro systems. Additionally, a comprehensive analysis of the cooperation during the process of binding and permeabilization is included.

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High-yield and cost-effective biosynthesis process for producing antimicrobial peptide AA139

Zhang,

Wang,

et al. 2024

Protein Expression and Purification

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Investigations into the membrane activity of arenicin antimicrobial peptide AA139

Cited by 7 publications

References 61 publications

In Vitro Modulation of Complement Activation by Therapeutically Prospective Analogues of the Marine Polychaeta Arenicin Peptides

In Vitro Modulation of Complement Activation by Therapeutically Prospective Analogues of the Marine Polychaeta Arenicin Peptides

Membrane permeability and antimicrobial peptides: Much more than just making a hole

High-yield and cost-effective biosynthesis process for producing antimicrobial peptide AA139

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