Chemical modifications of short antimicrobial peptides from insects and vertebrates to fight multi-drug resistant bacteria

Nanoparticles Enable Efficient Delivery of Antimicrobial Peptides for the Treatment of Deep Infections

BIO Integration ◽

10.15212/bioi-2021-0003 ◽

2021 ◽

Author(s):

Yingxue Deng ◽

Rui Huang ◽

Songyin Huang ◽

Menghua Xiong

Keyword(s):

Antimicrobial Peptides ◽

Broad Spectrum ◽

Antimicrobial Properties ◽

Therapeutic Index ◽

Resistant Bacteria ◽

Drug Resistant ◽

Drug Resistant Bacteria ◽

Efficient Delivery ◽

Delivery Vehicles

Antimicrobial peptides (AMPs) have emerged as promising alternatives of traditional antibiotics against drug-resistant bacteria owing to their broad-spectrum antimicrobial properties and low tendency to drugresistance. However, their therapeutic efficacy in vivo, especially for infections in deep organs, is limited owing to their systemic toxicity and low bioavailability. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Herein, we will discuss the current progress of using nanoparticles as delivery vehicles for AMPs for the treatment of deep infections.

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Design, Engineering and Discovery of Novel α-Helical and β-Boomerang Antimicrobial Peptides against Drug Resistant Bacteria

International Journal of Molecular Sciences ◽

10.3390/ijms21165773 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5773 ◽

Cited By ~ 7

Author(s):

Surajit Bhattacharjya ◽

Suzana K. Straus

Keyword(s):

Antimicrobial Peptides ◽

Resistant Bacteria ◽

Drug Resistant ◽

Antibiotic Development ◽

Extensively Drug Resistant ◽

Drug Resistant Bacteria ◽

Drying Up ◽

Further Development ◽

Lps Binding

In an era where the pipeline of new antibiotic development is drying up, the continuous rise of multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria are genuine threats to human health. Although antimicrobial peptides (AMPs) may serve as promising leads against drug resistant bacteria, only a few AMPs are in advanced clinical trials. The limitations of AMPs, namely their low in vivo activity, toxicity, and poor bioavailability, need to be addressed. Here, we review engineering of frog derived short α-helical AMPs (aurein, temporins) and lipopolysaccharide (LPS) binding designed β-boomerang AMPs for further development. The discovery of novel cell selective AMPs from the human proprotein convertase furin is also discussed.

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LAMP2: a major update of the database linking antimicrobial peptides

Database ◽

10.1093/database/baaa061 ◽

2020 ◽

Vol 2020 ◽

Cited By ~ 2

Author(s):

Guizi Ye ◽

Hongyu Wu ◽

Jinjiang Huang ◽

Wei Wang ◽

Kuikui Ge ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Primary Structure ◽

Scientific Community ◽

Resistant Bacteria ◽

Drug Resistant ◽

Current Version ◽

Functional Activities ◽

Drug Resistant Bacteria ◽

Functional Classes ◽

And Function

Abstract Antimicrobial peptides (AMPs) have been regarded as a potential weapon to fight against drug-resistant bacteria, which is threating the globe. Thus, more and more AMPs had been designed or identified. There is a need to integrate them into a platform for researchers to facilitate investigation and analyze existing AMPs. The AMP database has become an important tool for the discovery and transformation of AMPs as agents. A database linking antimicrobial peptides (LAMPs), launched in 2013, serves as a comprehensive tool to supply exhaustive information of AMP on a single platform. LAMP2, an updated version of LAMP, holds 23 253 unique AMP sequences and expands to link 16 public AMP databases. In the current version, there are more than 50% (12 236) sequences only linking a single database and more than 45% of AMPs linking two or more database links. Additionally, updated categories based on primary structure, collection, composition, source and function have been integrated into LAMP2. Peptides in LAMP2 have been integrated in 8 major functional classes and 38 functional activities. More than 89% (20 909) of the peptides are experimentally validated peptides. A total of 1924 references were extracted and regarded as the evidence for supporting AMP activity and cytotoxicity. The updated version will be helpful to the scientific community.

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Mass Balance Study of the Engineered Cationic Antimicrobial Peptide, WLBU2, Following a Single Intravenous Dose of 14C-WLBU2 in Mice.

Current Clinical Pharmacology ◽

10.2174/1574884715666200810094201 ◽

2020 ◽

Vol 15 ◽

Author(s):

Jan H. Beumera ◽

Jianxia Guo ◽

Evan C. Ray ◽

Jonas Scemama ◽

Robert A. Parise ◽

...

Keyword(s):

Multidrug Resistance ◽

Antimicrobial Peptides ◽

Mass Balance ◽

Bacterial Infections ◽

Resistant Bacteria ◽

Drug Resistant ◽

Balance Study ◽

Drug Resistant Bacteria ◽

Mouse Tissues ◽

Mass Balance Study

Background: To address multidrug resistance we developed engineered cationic antimicrobial peptides (eCAPs). Lead eCAP WLBU2 displays potent activity against drug-resistant bacteria and effectively treats lethal bacterial infections in mice reducing bacterial loads to undetectable levels in diverse organs. Background: To address multidrug resistance we developed engineered cationic antimicrobial peptides (eCAPs). Lead eCAP WLBU2 displays potent activity against drug-resistant bacteria and effectively treats lethal bacterial infections in mice reducing bacterial loads to undetectable levels in diverse organs. Objective: To support development of WLBU2, we conducted a mass balance study. Methods: CD1 mice were administered 10, 15, 20 and 30 mg/kg QDx5 WLBU2 or a single dose of [14C]-WLBU2 at 15 mg/kg IV. Tolerability, tissue distribution and excretion were evaluated with liquid scintillation and HPLCradiochromatography. Results: The maximum tolerated dose of WLBU2 is 20 mg/kg IV. We could account for greater than >96% of the radioactivity distributed within mouse tissues at 5 and 15 min. By 24 h, only ~40-50% of radioactivity remained in the mice. The greatest % of the dose was present in liver, accounting for ~35% of radioactivity at 5 and 15 min, and ~ 8% of radioactivity remained at 24 h. High radioactivity was also present in kidneys, plasma, red blood cells and lungs, while less than 0.2% of radioactivity was present in brain, fat, or skeletal muscle. Urinary and fecal excretion accounted for 12.5 and 2.2% of radioactivity at 24 h. Conclusion: WLBU2 distributes widely to mouse tissues and is rapidly cleared with a terminal radioactivity half-life of 22 h, a clearance of 27.4 mL/h/kg, and a distribution volume of 0.94 L/kg. At 2-100 µg-eq/g, the concentrations of 14CWLBU2 appear high enough in the tissues to account for inhibition of microbial growth.

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Studies on the Antibacterial Activity and Mechanism of Antimicrobial Peptides Against Drug-Resistant Bacteria

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2018.2528 ◽

2018 ◽

Vol 14 (3) ◽

pp. 601-608 ◽

Cited By ~ 7

Author(s):

Xiaofang Luo ◽

Yanjun Liu ◽

Zuodong Qin ◽

Zhiyuan Jin ◽

Liting Xu ◽

...

Keyword(s):

Antibacterial Activity ◽

Antimicrobial Peptides ◽

Resistant Bacteria ◽

Drug Resistant ◽

Drug Resistant Bacteria

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Conjugation of Silver Nanoparticles with De Novo Engineered Cationic Antimicrobial Peptides: Proposal for Study (Preprint)

10.2196/preprints.28307 ◽

2021 ◽

Author(s):

Alvin Hu

Keyword(s):

Antimicrobial Activity ◽

Silver Nanoparticles ◽

Minimum Inhibitory Concentration ◽

Antimicrobial Peptides ◽

Inhibitory Concentration ◽

De Novo ◽

Resistant Bacteria ◽

Drug Resistant ◽

Cationic Antimicrobial Peptides ◽

Drug Resistant Bacteria

BACKGROUND Cationic antimicrobial peptides have broad antimicrobial activity and provide a novel way of targeting multi drug resistant bacteria in an era of increasing antimicrobial resistance. Current developments show positive prospects for both antimicrobial peptides and silver nanoparticles individually. OBJECTIVE The primary objective is to propose another method of enhancing antimicrobial activity by conjugating silver nanoparticles with cationic antimicrobial peptides for a subsequent preliminary assessment on studying the minimum inhibitory concentration of multi drug resistant bacteria. The secondary objective would be to evaluate the safety of the conjugated compound to assess viability for in vivo use. METHODS The proposition is planned for approximately 3 overarching stages. Firstly, I propose synthesis of wlbu2c, a modified version of antimicrobial peptide wlbu2 with an added cysteine group, using standard Fmoc procedure. This will subsequently be attempted to stably conjugate with silver nanoparticles ideally through photochemical means. Secondly, the conjugate wlbu2c-AgNP will be tested for antimicrobial activity following Clinical & Laboratory Standards Institute Manual on standard minimum inhibitory concentration testing. If all of the above is completed the experiment can progress to the assessment of cytotoxicity using cell lysis assays. RESULTS I-TASSER simulation revealed that our modified peptide wlbu2c has similar secondary structure to original wlbu2 peptide. No other results have been obtained at this time other than aforementioned theoretical propositions. CONCLUSIONS The addition of silver nanoparticles to already developing de novo engineered antimicrobial peptides provide a second degree of freedom toward the development of potent antimicrobials. Future prospects include emergency last line therapy, treatment for current difficult to eradicate bacterial colonization such as in cystic fibrosis, implantable medical devices, cancer and immunotherapy. This proposal is intended to be provided to the public as I do not anticipate funding at this time.

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HAMP: A Knowledgebase of Antimicrobial Peptides from Human Microbiome.

Current Bioinformatics ◽

10.2174/1574893615999200802041228 ◽

2020 ◽

Vol 15 ◽

Author(s):

Viswajit Mulpuru ◽

Rahul Semwal ◽

Pritish Kumar Varadwaj ◽

Nidhi Mishra

Keyword(s):

Antimicrobial Peptides ◽

Human Microbiome ◽

Resistant Bacteria ◽

Drug Resistant ◽

Antimicrobial Drugs ◽

Candidate Peptide ◽

Drug Resistant Bacteria ◽

Query Engine ◽

Extended Analysis ◽

Drug Resistant Strains

Background: Antimicrobial peptides (AMPs) can defend the hosts against various pathogens and are found in almost every life form from microorganisms to humans. As the rapid increase of drug-resistant strains in recent years is presenting a serious challenge to healthcare, antimicrobial peptides (AMPs) can revolutionize the antimicrobial development against the drug-resistant microbes. Objective: The objective was to encourage the study on the human microbiome towards inhibition of drug-resistant bacteria by the development of a database containing antimicrobial peptides from the human microbiome. Method: This database is an outcome of an extended analysis of Human metagenome, involving the prediction of coding regions, extraction of peptides, prediction of antimicrobial peptides, and modeling their structure utilizing different in silico tools. Further, an intelligent hash function-based query engine was designed to validate the novelty of specific candidate peptide over the reported knowledgebase. Result and Discussion: This knowledgebase currently focuses on antimicrobial peptide sequences (AMPs) predicted from the human microbiome along with 3D their structures modeled using various modeling and molecular dynamics approaches. It includes a total of 1087 unique AMPs from various body sites, with 454 AMPs from the oral cavity, 180 AMPs from the gastrointestinal tract, 42 AMPs from the skin, 12 AMPs from the airway, 6 AMPs from the urogenital tract and 393 AMPs from undefined body locations. A scoring matrix has been generated based on the similarity scores of the sequences that have been incorporated into the knowledgebase. Further, a Jmol applet is included in the website to help users visualize the 3D structures. Conclusion: The information and functions of the knowledgebase can offer great help in finding novel antimicrobial drugs, especially towards finding inhibitors for drug-resistant bacteria. The HAMP is freely available at https://bioserver.iiita.ac.in/amp/index.html.

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Integration of antimicrobial peptides and gold nanorods for bimodal antibacterial applications

Biomaterials Science ◽

10.1039/d0bm00782j ◽

2020 ◽

Vol 8 (16) ◽

pp. 4447-4457

Author(s):

Jin Chen ◽

Tingting Dai ◽

Jiawei Yu ◽

Xiahong Dai ◽

Richai Chen ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Antimicrobial Peptide ◽

Gold Nanorods ◽

Bacterial Activity ◽

Resistant Bacteria ◽

Drug Resistant ◽

Drug Resistant Bacteria

We integrate the anti-bacterial activity of BF2b antimicrobial peptide and the photothermal sterilization of gold nanorods to kill drug-resistant bacteria.

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