scholarly journals Diversity, evolution and medical applications of insect antimicrobial peptides

2016 ◽  
Vol 371 (1695) ◽  
pp. 20150290 ◽  
Author(s):  
Eleftherios Mylonakis ◽  
Lars Podsiadlowski ◽  
Maged Muhammed ◽  
Andreas Vilcinskas
Keyword(s):  
Antimicrobial Peptides ◽  
High Throughput Screening ◽  
Rational Design ◽  
Evolutionary Ecology ◽  
Multidrug Resistant ◽  
Screening Methods ◽  
Medical Applications ◽  
Human Pathogens ◽  
Acinetobacter Baumanii ◽  
Multidrug Resistant Pathogens

Antimicrobial peptides (AMPs) are short proteins with antimicrobial activity. A large portion of known AMPs originate from insects, and the number and diversity of these molecules in different species varies considerably. Insect AMPs represent a potential source of alternative antibiotics to address the limitation of current antibiotics, which has been caused by the emergence and spread of multidrug-resistant pathogens. To get more insight into AMPs, we investigated the diversity and evolution of insect AMPs by mapping their phylogenetic distribution, allowing us to predict the evolutionary origins of selected AMP families and to identify evolutionarily conserved and taxon-specific families. Furthermore, we highlight the use of the nematode Caenorhabditis elegans as a whole-animal model in high-throughput screening methods to identify AMPs with efficacy against human pathogens, including Acinetobacter baumanii and methicillin-resistant Staphylococcus aureus . We also discuss the potential medical applications of AMPs, including their use as alternatives for conventional antibiotics in ectopic therapies, their combined use with antibiotics to restore the susceptibility of multidrug-resistant pathogens, and their use as templates for the rational design of peptidomimetic drugs that overcome the disadvantages of therapeutic peptides. The article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’.

scholarly journals Antiviral Compounds for Blocking Arboviral Transmission in Mosquitoes

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 108
Author(s):  
Shengzhang Dong ◽  
George Dimopoulos
Keyword(s):  
High Throughput Screening ◽  
Mammalian Cells ◽  
Symbiotic Bacterium ◽  
Screening Methods ◽  
Human Pathogens ◽  
Inhibitory Effects ◽  
Antiviral Compounds ◽  
Mosquito Cells ◽  
Recent Emergence ◽  
Arboviral Transmission

Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent need for safe and effective vaccines, therapeutics, and vector-control approaches to prevent MBVD outbreaks. In nature, arboviruses circulate between vertebrate hosts and arthropod vectors; therefore, disrupting the virus lifecycle in mosquitoes is a major approach for combating MBVDs. Several strategies were proposed to render mosquitoes that are refractory to arboviral infection, for example, those involving the generation of genetically modified mosquitoes or infection with the symbiotic bacterium Wolbachia. Due to the recent development of high-throughput screening methods, an increasing number of drugs with inhibitory effects on mosquito-borne arboviruses in mammalian cells were identified. These antivirals are useful resources that can impede the circulation of arboviruses between arthropods and humans by either rendering viruses more vulnerable in humans or suppressing viral infection by reducing the expression of host factors in mosquitoes. In this review, we summarize recent advances in small-molecule antiarboviral drugs in mammalian and mosquito cells, and discuss how to use these antivirals to block the transmission of MBVDs.

scholarly journals In Vitro Activities of Designed Antimicrobial Peptides against Multidrug-Resistant Cystic Fibrosis Pathogens

1999 ◽  
Vol 43 (6) ◽  
pp. 1435-1440 ◽  
Author(s):  
Ute Schwab ◽  
Peter Gilligan ◽  
Jesse Jaynes ◽  
David Henke
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Peptides ◽  
Burkholderia Cepacia ◽  
Wide Spectrum ◽  
Multidrug Resistant ◽  
Medium Composition ◽  
Peptide Antibiotics ◽  
Rpmi Medium ◽  
Multidrug Resistant Pathogens

ABSTRACT The emergence of multidrug-resistant pathogens renders antibiotics ineffective in the treatment of lung infections in patients with cystic fibrosis (CF). Designed antimicrobial peptides (DAPs) are laboratory-synthesized peptide antibiotics that demonstrate a wide spectrum of antibacterial activity. Optimal conditions for susceptibility testing of these peptides have not yet been established. Medium composition is clearly a major factor influencing the results and reproducibilities of susceptibility tests. Using time-kill assays, we tested the effects of different media and buffers on the bactericidal activities of the peptides D2A21 and D4E1 onStaphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 27853. Each peptide at 1 and 5 μM was incubated with bacteria in the different media and buffers. Both peptides were most active in Tris-HCl buffer against S. aureus andP. aeruginosa. Among the more complex media tested, modified RPMI medium was the medium in which the peptides demonstrated the highest activity, while it supported the growth of the bacteria. The broth microdilution technique was used to test the activities of D2A21 and D4E1 in modified RPMI medium against multidrug-resistant pathogens from patients with CF. The MICs of DAPs for methicillin-resistant S. aureus ranged from 0.25 to 4 μg/ml, those for multidrug-resistant P. aeruginosa ranged from 0.125 to 4 μg/ml, those for Stenotrophomonas maltophilia ranged from 0.5 to 32 μg/ml, and those forBurkholderia cepacia ranged from 32 to ≥64 μg/ml. When the activity of peptide D2A21 was compared with that of the tracheal antimicrobial peptide (TAP), D2A21 had greater potency than TAP againstP. aeruginosa. In addition, no difference in the MICs of D2A21 was seen when it was tested in nutrient broth supplemented with NaCl at different concentrations. Thus, DAPs are a class of salt-insensitive antibiotics potentially useful in the treatment of CF patients harboring multidrug-resistant P. aeruginosa.

scholarly journals Rational Design of Engineered Cationic Antimicrobial Peptides Consisting Exclusively of Arginine and Tryptophan, and Their Activity against Multidrug-Resistant Pathogens

2013 ◽  
Vol 57 (6) ◽  
pp. 2511-2521 ◽  
Author(s):  
Berthony Deslouches ◽  
Jonathan D. Steckbeck ◽  
Jodi K. Craigo ◽  
Yohei Doi ◽  
Timothy A. Mietzner ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Rational Design ◽  
Antimicrobial Agents ◽  
Divalent Cations ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Broth Culture ◽  
Cationic Antimicrobial Peptides ◽  
Content Type ◽  
Amphipathic Helices

ABSTRACTThe emergence of multidrug-resistant (MDR) pathogens underscores the need for new antimicrobial agents to overcome the resistance mechanisms of these organisms. Cationic antimicrobial peptides (CAPs) provide a potential source of new antimicrobial therapeutics. We previously characterized a lytic base unit (LBU) series of engineered CAPs (eCAPs) of 12 to 48 residues demonstrating maximum antibacterial selectivity at 24 residues. Further, Trp substitution in LBU sequences increased activity against bothP. aeruginosaandS. aureusunder challenging conditions (e.g., saline, divalent cations, and serum). Based on these findings, we hypothesized that the optimal length and, therefore, the cost for maximum eCAP activity under physiologically relevant conditions could be significantly reduced using only Arg and Trp arranged to form idealized amphipathic helices. Hence, we developed a novel peptide series, composed only of Arg and Trp, in a sequence predicted and verified by circular dichroism to fold into optimized amphipathic helices. The most effective antimicrobial activity was achieved at 12 residues in length (WR12) against a panel of both Gram-negative and Gram-positive clinical isolates, including extensively drug-resistant strains, in saline and broth culture and at various pH values. The results demonstrate that the rational design of CAPs can lead to a significant reduction in the length and the number of amino acids used in peptide design to achieve optimal potency and selectivity against specific pathogens.

Antibacterial activity of bacteria isolated from Phragmites australis against multidrug-resistant human pathogens

2021 ◽  
Vol 16 (5) ◽  
pp. 291-303
Author(s):  
Vania Delfino ◽  
Carmela Calonico ◽  
Antonella Lo Nostro ◽  
Lara Mitia Castronovo ◽  
Sara Del Duca ◽  
...  
Keyword(s):  
Phragmites Australis ◽  
Multidrug Resistant ◽  
Antimicrobial Compounds ◽  
Bacterial Endophytes ◽  
Human Pathogens ◽  
Natural Sources ◽  
New Antibiotics ◽  
Multidrug Resistant Pathogens ◽  
New Compounds ◽  
Novel Antibiotics

Background: Rising number of multidrug-resistant human pathogens demands novel antibiotics: to this aim, unexplored natural sources are investigated to find new compounds. In this context, bacteria associated to medicinal plants, including Phragmites australis, might represent an important source of antimicrobial compounds. Materials & methods: In the present work, 21 bacterial endophytes isolated from P. australis roots were tested, by cross-streaking, for their inhibitory activity against 36 multidrug-resistant pathogens isolated from food, clinical patients and hospitals. Results & conclusion: Seven endophytes, belonging to Pseudomonas and Stenotrophomonas, were able to inhibit the growth of most of the target strains. In conclusion, this preliminary work could pave the way for the discovery of new antibiotics against superbugs.

scholarly journals Antimicrobial Peptides: A Potent Alternative to Antibiotics

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1095
Author(s):  
Mariam Rima ◽  
Mohamad Rima ◽  
Ziad Fajloun ◽  
Jean-Marc Sabatier ◽  
Burkhard Bechinger ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Therapeutic Applications ◽  
Multidrug Resistant Pathogens ◽  
Near Future

Antimicrobial peptides constitute one of the most promising alternatives to antibiotics since they could be used to treat bacterial infections, especially those caused by multidrug-resistant pathogens. Many antimicrobial peptides, with various activity spectra and mechanisms of actions, have been described. This review focuses on their use against ESKAPE bacteria, especially in biofilm treatments, their synergistic activity, and their application as prophylactic agents. Limitations and challenges restricting therapeutic applications are highlighted, and solutions for each challenge are evaluated to analyze whether antimicrobial peptides could replace antibiotics in the near future.

Combining Antimicrobial Peptides with Nanotechnology: An Emerging Field in Theranostics

2020 ◽  
Vol 21 (4) ◽  
pp. 413-428 ◽  
Author(s):  
Sk Abdul Mohid ◽  
Anirban Bhunia
Keyword(s):  
Quantum Dots ◽  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Toxicity Profile ◽  
Rapid Adaptation ◽  
New Antibiotics ◽  
Low Toxicity ◽  
Multidrug Resistant Pathogens ◽  
New Generation

The emergence of multidrug-resistant pathogens and their rapid adaptation against new antibiotics is a major challenge for scientists and medical professionals. Different approaches have been taken to combat this problem, which includes rationally designed potent antimicrobial peptides (AMPs) and several nanoparticles and quantum dots. AMPs are considered as a new generation of super antibiotics that hold enormous potential to fight against bacterial resistance by the rapidly killing planktonic as well as their biofilm form while keeping low toxicity profile against eukaryotic cells. Various nanoparticles and quantum dots have proved their effectiveness against a vast array of infections and diseases. Conjugation and functionalization of nanoparticles with potentially active antimicrobial peptides have added advantages that widen their applications in the field of drug discovery as well as delivery system including imaging and diagnostics. This article reviews the current progress and implementation of different nanoparticles and quantum dots conjugated antimicrobial peptides in terms of bio-stability, drug delivery, and therapeutic applications.

scholarly journals Microbiological evaluation of antibacterial potentiality of some edible plant extracts against multidrug resistant (MDR) human pathogens

2014 ◽  
Vol 4 (1) ◽  
pp. 336-339 ◽  
Author(s):  
Mohamed Helal El-Sayed ◽  
Bahgat Mohamed Refaat ◽  
Mohamed Hamed Sharaf
Keyword(s):  
Allium Cepa ◽  
Plant Extracts ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Thymus Vulgaris ◽  
Human Pathogens ◽  
Foeniculum Vulgare ◽  
Edible Plant ◽  
Acinetobacter Baumanii ◽  
Wide Range

Antimicrobial resistance is a subject of great concern in public health and also in the designing of strategies for current therapeutic protocols all over the world. Plants used for traditional medicine contain a wide range of substances which can be used to treat various infectious diseases. Hence, antibacterial activities of aqueous extracts of 10 plant species were studied against 25 multidrug resistant (MDR) clinical isolates using the agar well diffusion method. The most resistant organisms were Acinetobacter baumanii (A. baumanii) (resistant to 16 different antibiotics), Enterococcus faecium (E. faecium) (resistant to 15 different antibiotics), Pseudomonas aeruginosa (P. aeruginosa) (resistant to 15 antibiotics), Gemella morbillorum (G. morbillorum) (resistant to 14 different antibiotics), Enterobacter cloacae (E. cloacae) (resistant to 13 different antibiotics) respectively. Among the tested plant extracts, only extracts of Allium cepa, Allium sativum, Foeniculum vulgare, Matricaria chmomilla, Salvia offcinalis and Thymus Vulgaris showed strong antibacterial activity against MDR isolates with inhibition zones ranging from 8.33 to 26 mm. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the most active plant extracts; Allium cepa and Foeniculum vulgare were ranged from 0.062 to 0.25 mg/ml and 0.031 to 0.125 mg/ml, respectively. Foeniculum vulgare extract was bactericidal for all bacteria while Allium cepa extract was bacteriostatic. Hence, the discovered compounds from these plants can use as templates for the development of new antibacterial agents.DOI: http://dx.doi.org/10.3329/icpj.v4i1.21162 International Current Pharmaceutical Journal, December 2014, 4(1): 336-339

scholarly journals Proteomic Screening for Prediction and Design of Antimicrobial Peptides with AmpGram

2020 ◽  
Vol 21 (12) ◽  
pp. 4310 ◽  
Author(s):  
Michał Burdukiewicz ◽  
Katarzyna Sidorczuk ◽  
Dominik Rafacz ◽  
Filip Pietluch ◽  
Jarosław Chilimoniuk ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Rational Design ◽  
R Package ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antimicrobial Protein ◽  
Microbial Competition ◽  
Bacterial Membranes ◽  
Proteomic Screening ◽  
Prediction Reliability

Antimicrobial peptides (AMPs) are molecules widespread in all branches of the tree of life that participate in host defense and/or microbial competition. Due to their positive charge, hydrophobicity and amphipathicity, they preferentially disrupt negatively charged bacterial membranes. AMPs are considered an important alternative to traditional antibiotics, especially at the time when multidrug-resistant bacteria being on the rise. Therefore, to reduce the costs of experimental research, robust computational tools for AMP prediction and identification of the best AMP candidates are essential. AmpGram is our novel tool for AMP prediction; it outperforms top-ranking AMP classifiers, including AMPScanner, CAMPR3R and iAMPpred. It is the first AMP prediction tool created for longer AMPs and for high-throughput proteomic screening. AmpGram prediction reliability was confirmed on the example of lactoferrin and thrombin. The former is a well known antimicrobial protein and the latter a cryptic one. Both proteins produce (after protease treatment) functional AMPs that have been experimentally validated at molecular level. The lactoferrin and thrombin AMPs were located in the antimicrobial regions clearly detected by AmpGram. Moreover, AmpGram also provides a list of shot 10 amino acid fragments in the antimicrobial regions, along with their probability predictions; these can be used for further studies and the rational design of new AMPs. AmpGram is available as a web-server, and an easy-to-use R package for proteomic analysis at CRAN repository.

scholarly journals Effects of Rationally Designed Physico-Chemical Variants of the Peptide PuroA on Biocidal Activity towards Bacterial and Mammalian Cells

2020 ◽  
Vol 21 (22) ◽  
pp. 8624
Author(s):  
Nadin Shagaghi ◽  
Andrew H. A. Clayton ◽  
Marie-Isabel Aguilar ◽  
Tzong-Hsien Lee ◽  
Enzo A. Palombo ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Rational Design ◽  
Wide Spectrum ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Human Pathogens ◽  
Chemical Parameters ◽  
Net Charge ◽  
Rich Domain ◽  
Physico Chemical

Antimicrobial peptides (AMPs) often exhibit wide-spectrum activities and are considered ideal candidates for effectively controlling persistent and multidrug-resistant wound infections. PuroA, a synthetic peptide based on the tryptophan (Trp)-rich domain of the wheat protein puroindoline A, displays strong antimicrobial activities. In this work, a number of peptides were designed based on PuroA, varying in physico-chemical parameters of length, number of Trp residues, net charge, hydrophobicity or amphipathicity, D-versus L-isomers of amino acids, cyclization or dimerization, and were tested for antimicrobial potency and salt and protease tolerance. Selected peptides were assessed for effects on biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and selected mammalian cells. Peptide P1, with the highest amphipathicity, six Trp and a net charge of +7, showed strong antimicrobial activity and salt stability. Peptides W7, W8 and WW (seven to eight residues) were generally more active than PuroA and all diastereomers were protease-resistant. PuroA and certain variants significantly inhibited initial biomass attachment and eradicated preformed biofilms of MRSA. Further, P1 and dimeric PuroA were cytotoxic to HeLa cells. The work has led to peptides with biocidal effects on common human pathogens and/or anticancer potential, also offering great insights into the relationship between physico-chemical parameters and bioactivities, accelerating progress towards rational design of AMPs for therapeutics.

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