International Journal of Molecular Sciences

Journal Browser

► Journal Browser

Special Issue Information

Dear Colleagues,

The surge in antibiotic-resistant bacteria demands the development of new antimicrobials with novel modes of action. Antimicrobial peptides (AMPs) or host defense AMPs have gained high prominence in this regard. AMPs can demonstrate multifunctional activity including the killing of drug-resistant bacterial pathogens, wound healing, antibiotic potentiators (adjuvants), immunomodulation, and endotoxic neutralization. The design, engineering, chemical modifications, and bio-conjugations of AMPs can pave the way for next-generation antimicrobial therapeutics. Template-based design of potent AMPs would require an understating of the mode of action and structural basis of their activity. This Special Issue will focus on atomic-resolution structures and interactions of AMPs with their cognate biological/bacterial targets. Papers presenting the development of novel imaging methods to examine the mode of action and interactions of AMPs are solicited.

Dr. Surajit Bhattacharjya
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

antimicrobial peptides
host defense peptides
structrues
design of antimcrobial peptides
membrane interacitons
protein complex

Published Papers (2 papers)

Download All Papers

Research

Jump to: Review

17 pages, 3900 KiB

Open AccessArticle

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

by Swaleeha Jaan Abdullah, Bernice Tan Siu Yan, Nithya Palanivelu, Vidhya Bharathi Dhanabal, Juan Pablo Bifani and Surajit Bhattacharjya

Int. J. Mol. Sci. 2024, 25(4), 2122; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25042122 - 09 Feb 2024

Cited by 1 | Viewed by 888

Abstract

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 LptA_m 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 LptA_m 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. Full article

(This article belongs to the Special Issue State-of-the-Art Antimicrobial Peptides in the Era of Antibiotic Resistance)

► Show Figures

Figure 1

Review

Jump to: Research

18 pages, 6220 KiB

Open AccessReview

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

by Maria Luisa Mangoni, Maria Rosa Loffredo, Bruno Casciaro, Loretta Ferrera and Floriana Cappiello

Int. J. Mol. Sci. 2024, 25(8), 4400; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25084400 - 16 Apr 2024

Viewed by 420

Abstract

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. Full article

(This article belongs to the Special Issue State-of-the-Art Antimicrobial Peptides in the Era of Antibiotic Resistance)

► Show Figures