Distinct mode of membrane interaction and disintegration by diverse class of antimicrobial peptides

Agadi, Nutan; Maity, Atanu; Jha, Akash K.; Chakrabarti, Ramananda; Kumar, Ashutosh

doi:10.1016/j.bbamem.2022.184047

Cited by 6 publications

(6 citation statements)

References 55 publications

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“…AMPs are gene-encoded molecules containing from 10 to 50 amino acids, generally produced as prepropeptides [32,33] by almost all living organisms as key components of the host innate immune system [34]. Although AMPs differ in their chain length, sequence, and secondary structure, most of them are cationic molecules at physiological pH, with an amphipathic character in a membrane-mimicking environment, which are two fundamental features for their mechanism of microbial killing [35,36]. Indeed, especially for the cationic alpha-helical AMPs, this mechanism is based on an initial electrostatic interaction with the negatively-charged components of the microbial cell surface (like lipopolysaccharides, LPS, in Gram-negative bacteria), to subsequently reach the target bacterial cytoplasmic membrane that is much richer in anionic phospholipids, i.e., phosphatidylglycerol and cardiolipin, than the membrane of mammalian cells, which is mainly made of electrically neutral counterparts [37].…”

Section: Antimicrobial Peptides (Amps)mentioning

confidence: 99%

An Overview of Frog Skin-Derived Esc Peptides: Promising Multifunctional Weapons against Pseudomonas aeruginosa-Induced Pulmonary and Ocular Surface Infections

Mangoni,

Loffredo,

Casciaro

et al. 2024

IJMS

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Antimicrobial resistance is a silent pandemic harming human health, and Pseudomonas aeruginosa is the most common bacterium responsible for chronic pulmonary and eye infections. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics. In this review, the in vitro/in vivo activities of the frog skin-derived AMP Esc(1-21) are shown. Esc(1-21) rapidly kills both the planktonic and sessile forms of P. aeruginosa and stimulates migration of epithelial cells, likely favoring repair of damaged tissue. However, to undertake preclinical studies, some drawbacks of AMPs (cytotoxicity, poor biostability, and limited delivery to the target site) must be overcome. For this purpose, the stereochemistry of two amino acids of Esc(1-21) was changed to obtain the diastereomer Esc(1-21)-1c, which is more stable, less cytotoxic, and more efficient in treating P. aeruginosa-induced lung and cornea infections in mouse models. Incorporation of these peptides (Esc peptides) into nanoparticles or immobilization to a medical device (contact lens) was revealed to be an effective strategy to ameliorate and/or to prolong the peptides’ antimicrobial efficacy. Overall, these data make Esc peptides encouraging candidates for novel multifunctional drugs to treat lung pathology especially in patients with cystic fibrosis and eye dysfunctions, characterized by both tissue injury and bacterial infection.

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Section: Antimicrobial Peptides (Amps)mentioning

confidence: 99%

An Overview of Frog Skin-Derived Esc Peptides: Promising Multifunctional Weapons against Pseudomonas aeruginosa-Induced Pulmonary and Ocular Surface Infections

Mangoni,

Loffredo,

Casciaro

et al. 2024

IJMS

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“…In an assay mimicking a bacterial membrane, treatment with a bovine cathelicidin, BMAP-28 disrupted the packing of the bilayer, resulting in thinning of the membrane and pore formation (Agadi et al, 2022). This mechanism is shared among other members of the cathelicidin family with alpha-helical structures, such as LL-37, Dermcidin, BMAP-27, indolicidin and PMAP-36 (Agadi et al, 2022;Waz et al, 2022). Conversely, in pore-less models, the CAMPs do not transverse the membrane but instead cover it, like a carpet.…”

Section: Antimicrobial Properties Of Cathelicidins and Therapeutic Ap...mentioning

confidence: 99%

“…In the toroidal model, the peptides are adsorbed to the lipid bilayer at low concentrations, and at high concentrations, they insert vertically into the bilayer. In an assay mimicking a bacterial membrane, treatment with a bovine cathelicidin, BMAP-28 disrupted the packing of the bilayer, resulting in thinning of the membrane and pore formation ( Agadi et al, 2022 ). This mechanism is shared among other members of the cathelicidin family with alpha-helical structures, such as LL-37, Dermcidin, BMAP-27, indolicidin and PMAP-36 ( Agadi et al, 2022 ; Waz et al, 2022 ).…”

Section: Antimicrobial Properties Of Cathelicidins and Therapeutic Ap...mentioning

confidence: 99%

“…modulation, antitumoral effect; auto-immune diseases controlNiemirowicz et al (2016),Shahmiri et al (2016), van Harten et al (2018,Matougui et al (2019),Mookherjee et al (2020),Nagaoka et al (2020),Sancho-Vaello et al (2020),Wang et al (2021),Yu et al (2021),Agadi et al (2022),Duan et al (2022),Lokhande et al (2022),Waz et al (2022Waz et al ( . (2010, Umeshappa et al (2021), Duan et al (2022), and Yang et al (2023) PMAP-36 Pig Antimicrobial, immune modulation Agadi et al (2022) and Waz et al (2022) modulation; antitumoral effect; auto-immune diseases control Kosciuczuk et al (2012), Niemirowicz et al (2016), Matougui et al (2019), Rowe-Magnus et al (2019), Browne et al (2020), Qi et al (2020), Wnorowska et al (2020), Dijksteel et al (2021), and Cristelo et al…”

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confidence: 99%

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Recent advances in the therapeutic potential of cathelicidins

Guerra,

Vieira,

Calazans

et al. 2024

Front. Microbiol.

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The alarming increase in antimicrobial resistance in the last decades has prompted the search for alternatives to control infectious diseases. Antimicrobial peptides (AMPs) represent a heterogeneous class of molecules with ample antibacterial, antiviral, and antifungal effects. They can be found in many organisms, including all classes of vertebrates, providing a valuable source of new antimicrobial agents. The unique properties of AMPs make it harder for microbes develop resistance, while their immunomodulatory properties and target diversity reinforce their translational use in multiple diseases, from autoimmune disorders to different types of cancer. The latest years have witnessed a vast number of studies evaluating the use of AMPs in therapy, with many progressing to clinical trials. The present review explores the recent developments in the medicinal properties of cathelicidins, a vast family of AMPs with potent antimicrobial and immunomodulatory effects. Cathelicidins from several organisms have been tested in disease models of viral and bacterial infections, inflammatory diseases, and tumors, with encouraging results. Combining nanomaterials with active, natural antimicrobial peptides, including LL-37 and synthetic analogs like ceragenins, leads to the creation of innovative nanoagents with significant clinical promise. However, there are still important limitations, such as the toxicity of many cathelicidins to healthy host cells and low stability in vivo. The recent advances in nanomaterials and synthetic biology may help overcome the current limitations, enabling the use of cathelicidins in future therapeutics. Furthermore, a better understanding of the mechanisms of cathelicidin action in vivo and their synergy with other host molecules will contribute to the development of safer, highly effective therapies.

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“…Host defense AMPs contain a high potential to combat drug or multidrug-resistant bacterial pathogens. AMPs are evolutionary conserved molecules found in all kingdoms of life that are effective in fending off infections as a part of innate immunity [14][15][16][17]. The broad-spectrum activity of AMPs provides vital lead molecules for the next generation of antibiotics [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Outer-Membrane Permeabilization, LPS Transport Inhibition: Activity, Interactions, and Structures of Thanatin Derived Antimicrobial Peptides

Abdullah,

Yan,

Palanivelu

et al. 2024

IJMS

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Currently, viable antibiotics available to mitigate infections caused by drug-resistant Gram-negative bacteria are highly limited. Thanatin, a 21-residue-long insect-derived antimicrobial peptide (AMP), is a promising lead molecule for the potential development of novel antibiotics. Thanatin is extremely potent, particularly against the Enterobacter group of Gram-negative pathogens, e.g., E. coli and K. pneumoniae. As a mode of action, cationic thanatin efficiently permeabilizes the LPS-outer membrane and binds to the periplasmic protein LptAm to inhibit outer membrane biogenesis. Here, we have utilized N-terminal truncated 16- and 14-residue peptide fragments of thanatin and investigated structure, activity, and selectivity with correlating modes of action. A designed 16-residue peptide containing D-Lys (dk) named VF16 (V1PIIYCNRRT-dk-KCQRF16) demonstrated killing activity in Gram-negative bacteria. The VF16 peptide did not show any detectable toxicity to the HEK 293T cell line and kidney cell line Hep G2. As a mode of action, VF16 interacted with LPS, permeabilizing the outer membrane and binding to LptAm with high affinity. Atomic-resolution structures of VF16 in complex with LPS revealed cationic and aromatic surfaces involved in outer membrane interactions and permeabilization. Further, analyses of an inactive 14-residue native thanatin peptide (IM14: IIYCNRRTGKCQRM) delineated the requirement of the β-sheet structure in activity and target interactions. Taken together, this work would pave the way for the designing of short analogs of thanatin-based antimicrobials.

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Distinct mode of membrane interaction and disintegration by diverse class of antimicrobial peptides

Cited by 6 publications

References 55 publications

An Overview of Frog Skin-Derived Esc Peptides: Promising Multifunctional Weapons against Pseudomonas aeruginosa-Induced Pulmonary and Ocular Surface Infections

An Overview of Frog Skin-Derived Esc Peptides: Promising Multifunctional Weapons against Pseudomonas aeruginosa-Induced Pulmonary and Ocular Surface Infections

Recent advances in the therapeutic potential of cathelicidins

Outer-Membrane Permeabilization, LPS Transport Inhibition: Activity, Interactions, and Structures of Thanatin Derived Antimicrobial Peptides

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