scholarly journals Antimicrobial Peptides: Recent Insights on Biotechnological Interventions and Future Perspectives

2019 ◽  
Vol 26 (2) ◽  
pp. 79-87 ◽  
Author(s):  
Rajeshwari Sinha ◽  
Pratyoosh Shukla
Keyword(s):  
Antimicrobial Peptides ◽  
Gene Editing ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Future Perspectives ◽  
Antibiotic Resistant ◽  
Viable Solution ◽  
New Antibiotics ◽  
Potential Applications ◽  
Critical Public Health

With the unprecedented rise of drug-resistant pathogens, particularly antibiotic-resistant bacteria, and no new antibiotics in the pipeline over the last three decades, the issue of antimicrobial resistance has emerged as a critical public health threat. Antimicrobial Peptides (AMP) have garnered interest as a viable solution to this grave issue and are being explored for their potential antimicrobial applications. Given their low bioavailability in nature, tailoring new AMPs or strategizing approaches for increasing the yield of AMPs, therefore, becomes pertinent. </P><P> The present review focuses on biotechnological interventions directed towards enhanced AMP synthesis and revisits existing genetic engineering and synthetic biology strategies for production of AMPs. This review further underscores the importance and potential applications of advanced gene editing technologies for the synthesis of novel AMPs in future.

scholarly journals Fosfomycin

2016 ◽  
Vol 29 (2) ◽  
pp. 321-347 ◽  
Author(s):  
Matthew E. Falagas ◽  
Evridiki K. Vouloumanou ◽  
George Samonis ◽  
Konstantinos Z. Vardakas
Keyword(s):  
Bacterial Infections ◽  
Clinical Effectiveness ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Development Of Resistance ◽  
Extensively Drug Resistant ◽  
New Antibiotics

SUMMARYThe treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, thein vitroactivity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

scholarly journals Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects

2020 ◽  
Vol 7 (4) ◽  
pp. 206
Author(s):  
Rohit Kumar ◽  
Syed Azmal Ali ◽  
Sumit Kumar Singh ◽  
Vanya Bhushan ◽  
Manya Mathur ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Wide Spectrum ◽  
Farm Animals ◽  
Resistant Bacteria ◽  
Clinical Implementation ◽  
Antibiotic Resistant ◽  
Systematic Classification ◽  
New Antibiotics ◽  
Host Defense System ◽  
Prospective Application

Antimicrobial peptides (AMPs) are the arsenals of the innate host defense system, exhibiting evolutionarily conserved characteristics that are present in practically all forms of life. Recent years have witnessed the emergence of antibiotic-resistant bacteria compounded with a slow discovery rate for new antibiotics that have necessitated scientific efforts to search for alternatives to antibiotics. Research on the identification of AMPs has generated very encouraging evidence that they curb infectious pathologies and are also useful as novel biologics to function as immunotherapeutic agents. Being innate, they exhibit the least cytotoxicity to the host and exerts a wide spectrum of biological activity including low resistance among microbes and increased wound healing actions. Notably, in veterinary science, the constant practice of massive doses of antibiotics with inappropriate withdrawal programs led to a high risk of livestock-associated antimicrobial resistance. Therefore, the world faces tremendous pressure for designing and devising strategies to mitigate the use of antibiotics in animals and keep it safe for posterity. In this review, we illustrate the diversity of farm animal-specific AMPs, and their biochemical foundations, mode of action, and prospective application in clinics. Subsequently, we present the data for their systematic classification under the major and minor groups, antipathogenic action, and allied bioactivities in the host. Finally, we address the limitations of their clinical implementation and envision areas for further advancement.

scholarly journals Enhancing the Thermo-Stability and Anti-Bacterium Activity of Lysozyme by Immobilization on Chitosan Nanoparticles

2020 ◽  
Vol 21 (5) ◽  
pp. 1635 ◽  
Author(s):  
Yanan Wang ◽  
Shangyong Li ◽  
Mengfei Jin ◽  
Qi Han ◽  
Songshen Liu ◽  
...  
Keyword(s):  
Chitosan Nanoparticles ◽  
Antibacterial Properties ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Transmission Electron ◽  
Recent Emergence ◽  
New Antibiotics ◽  
Potential Applications ◽  
Thermo Stability

The recent emergence of antibiotic-resistant bacteria requires the development of new antibiotics or new agents capable of enhancing antibiotic activity. Lysozyme degrades bacterial cell wall without involving antibiotic resistance and has become a new antibacterial strategy. However, direct use of native, active proteins in clinical settings is not practical as it is fragile under various conditions. In this study, lysozyme was integrated into chitosan nanoparticles (CS-NPs) by the ionic gelation technique to obtain lysozyme immobilized chitosan nanoparticles (Lys-CS-NPs) and then characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), which showed a small particle size (243.1 ± 2.1 nm) and positive zeta potential (22.8 ± 0.2 mV). The immobilization significantly enhanced the thermal stability and reusability of lysozyme. In addition, compared with free lysozyme, Lys-CS-NPs exhibited superb antibacterial properties according to the results of killing kinetics in vitro and measurement of the minimum inhibitory concentration (MIC) of CS-NPs and Lys-CS-NPs against Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus). These results suggest that the integration of lysozyme into CS-NPs will create opportunities for the further potential applications of lysozyme as an anti-bacterium agent.

scholarly journals Antibody-Recruiting Protein-Catalyzed Capture Agents to Combat Antibiotic-Resistant Bacteria

2019 ◽  
Author(s):  
Matthew N. Idso ◽  
Ajay Suresh Akhade ◽  
Mario L. Arrieta-Ortiz ◽  
Bert T. Lai ◽  
Vivek Srinivas ◽  
...  
Keyword(s):  
Rapid Development ◽  
Bacterial Species ◽  
Surface Protein ◽  
Resistant Bacteria ◽  
Synthetic Approach ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Drug Resistant Bacteria ◽  
New Antibiotics ◽  
Drug Resistant Strains

AbstractAntibiotic resistant infections are projected to cause over 10 million deaths by 2050, yet the development of new antibiotics has slowed. This points to an urgent need for methodologies for the rapid development of antibiotics against emerging drug resistant pathogens. We report on a generalizable combined computational and synthetic approach, called antibody-recruiting protein-catalyzed capture agents (AR-PCCs), to address this challenge. We applied the combinatorial PCC technology to identify macrocyclic peptide ligands against highly conserved surface protein epitopes of carbapenem-resistant Klebsiella pneumoniae, an opportunistic gram-negative pathogen with drug resistant strains. Multi-omic data combined with bioinformatic analyses identified epitopes of the highly expressed MrkA surface protein of K. pneumoniae for targeting in PCC screens. The top-performing ligand exhibited high-affinity (EC50∼50 nM) to full-length MrkA, and selectively bound to MrkA-expressing K. pneumoniae, but not to other pathogenic bacterial species. AR-PCCs conjugated with immunogens promoted antibody recruitment to K. pneumoniae, leading to phagocytosis and phagocytic killing by macrophages. The rapid development of this highly targeted antibiotic implies that the integrated computational and synthetic toolkit described here can be used for the accelerated production of antibiotics against drug resistant bacteria.

Novel Antibiotics from Marine Sources

2011 ◽  
Vol 4 (3) ◽  
pp. 1446-1461 ◽  
Author(s):  
E.A. Martis ◽  
G M Doshi ◽  
G V Aggarwal ◽  
P P Shanbhag
Keyword(s):  
Pharmaceutical Industry ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Terrestrial Life ◽  
New Antibiotics ◽  
Antibiotic Compounds ◽  
New Generation ◽  
Novel Antibiotics ◽  
Untapped Resource

With the emergence of newer diseases, resistant forms of infectious diseases and multi-drug resistant bacteria, it has become essential to develop novel and more effective antibiotics. Current antibiotics are obtained from terrestrial life or made synthetically from intermediates. The ocean represents virtually untapped resource from which novel antibiotic compounds can be discovered. It is the marine world that will provide the pharmaceutical industry with the next generation of antibiotics. Marine antibiotics are antibiotics obtained from marine organisms. Scientists have reported the discovery of various antibiotics from marine bacteria (aplasmomycin, himalomycins, and pelagiomycins), sponges (Ara C, variabillin, strobilin, ircinin-1, aeroplysin, 3,5-dibromo-4-hydroxyphenylacetamide), coelenterates (asperidol and eunicin), mollusks (laurinterol and pachydictyol), tunicates (geranylhydroquinone and cystadytins), algae (cycloeudesmol, aeroplysinin-1(+), prepacifenol and tetrabromoheptanone), worms (tholepin and 3,5-dibromo-4-hydroxybezaldehyde), and actinomycetes (marinomycins C and D). This indicates that the marine environment, representing approximately half of the global diversity, is an enormous resource for new antibiotics and this source needs to be explored for the discovery of new generation antibiotics. The present article provides an overview of various antibiotics obtained from marine sources.

scholarly journals Antibiotic Pipeline Coordinators

2018 ◽  
Vol 46 (S1) ◽  
pp. 25-31 ◽  
Author(s):  
Enrico Baraldi ◽  
Olof Lindahl ◽  
Miloje Savic ◽  
David Findlay ◽  
Christine Årdal
Keyword(s):  
Research And Development ◽  
World Health ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Priority List ◽  
Non Profit ◽  
Global Priority ◽  
The World ◽  
New Antibiotics ◽  
Health Organization

The World Health Organization (WHO) has published a global priority list of antibiotic-resistant bacteria to guide research and development (R&D) of new antibiotics. Every pathogen on this list requires R&D activity, but some are more attractive for private sector investments, as evidenced by the current antibacterial pipeline. A “pipeline coordinator” is a governmental/non-profit organization that closely tracks the antibacterial pipeline and actively supports R&D across all priority pathogens employing new financing tools.

scholarly journals A Degradation Product from Hydrolysate of Imipenem with Imis Broad-Spectrum Inhibits Metallo-β-Lactamases

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Ying Ge ◽  
Li-Wei Xu ◽  
Jian-Bin Zhen ◽  
Cheng Chen ◽  
Miao Lv ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Degradation Product ◽  
Substrate Inhibition ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Leaving Group ◽  
Ic50 Values ◽  
Hydrolysis Of

Background: Infections caused by metallo-β-lactamases (MβLs)-producing antibiotic-resistant bacteria pose a severe threat to public health. The synergistic use of current antibiotics in combination with MβL inhibitors is a promising therapeutic mode against these antibiotic-resistant bacteria. Objectives: The study aimed to probe the inhibition of MβLs and obtain the active component, P1, in the degradation product after imipenem was hydrolyzed by ImiS. Methods: The hydrolysis of two carbapenems with MβL ImiS was monitored by UV-Vis in real-time, and the degradation product from the leaving group produced after imipenem was hydrolyzed (but not for faropenem) was purified by HPLC to give one component, P1. Results: Kinetic assays revealed that P1 exhibited a broad-spectrum inhibition against VIM-2, NDM-1, ImiS, and L1, from three sub-classes of MβLs, with IC50 values of 8 - 32, 13.8 - 29.3, and 14.2 - 19.2 µM, using imipenem, cefazolin, and nitrocefin as substrates, respectively. Also, P1 showed synergistic antibacterial efficacy against drug-resistant Escherichia coli producing VIM-2, NDM-1, ImiS, and L1, in combination with antibiotics, restoring 16 to 32-fold and 32 to 128-fold efficacies of imipenem and cefazolin, respectively. Spectroscopic and Ellman's reagent analyses suggested that P1, a mercaptoethyl-form imidamide, is a mechanism-based inhibitor, while faropenem has no substrate inhibition, due to the lack of a leaving group. Conclusions: This work reveals that the hydrolysate of imipenem, a carbapenem with a good leaving group, can be used in screening for broad-spectrum inhibitors of MβLs.

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

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.

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

2020 ◽  
Vol 21 (16) ◽  
pp. 5773 ◽  
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.

scholarly journals Thinking Outside the Bug: Molecular Targets and Strategies to Overcome Antibiotic Resistance

2019 ◽  
Vol 20 (6) ◽  
pp. 1255 ◽  
Author(s):  
Ana Monserrat-Martinez ◽  
Yann Gambin ◽  
Emma Sierecki
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Rational Design ◽  
Disease Onset ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
New Antibiotics ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Antibiotic Discovery

Since their discovery in the early 20th century, antibiotics have been used as the primary weapon against bacterial infections. Due to their prophylactic effect, they are also used as part of the cocktail of drugs given to treat complex diseases such as cancer or during surgery, in order to prevent infection. This has resulted in a decrease of mortality from infectious diseases and an increase in life expectancy in the last 100 years. However, as a consequence of administering antibiotics broadly to the population and sometimes misusing them, antibiotic-resistant bacteria have appeared. The emergence of resistant strains is a global health threat to humanity. Highly-resistant bacteria like Staphylococcus aureus (methicillin-resistant) or Enterococcus faecium (vancomycin-resistant) have led to complications in intensive care units, increasing medical costs and putting patient lives at risk. The appearance of these resistant strains together with the difficulty in finding new antimicrobials has alarmed the scientific community. Most of the strategies currently employed to develop new antibiotics point towards novel approaches for drug design based on prodrugs or rational design of new molecules. However, targeting crucial bacterial processes by these means will keep creating evolutionary pressure towards drug resistance. In this review, we discuss antibiotic resistance and new options for antibiotic discovery, focusing in particular on new alternatives aiming to disarm the bacteria or empower the host to avoid disease onset.

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