scholarly journals Therapeutic Potential of a Scorpion Venom-Derived Antimicrobial Peptide and Its Homologs Against Antibiotic-Resistant Gram-Positive Bacteria

2018 ◽  
Vol 9 ◽  
Author(s):  
Gaomin Liu ◽  
Fan Yang ◽  
Fangfang Li ◽  
Zhongjie Li ◽  
Yange Lang ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Di Zhang ◽  
Jingyi Chen ◽  
Qian Jing ◽  
Zheng Chen ◽  
Azeem Ullah ◽  
...  

The emergence of antibiotic-resistant bacteria poses a serious challenge to medical practice worldwide. A small peptide with sequence RWRWRW was previously identified as a core antimicrobial peptide with limited antimicrobial spectrum to bacteria, especially Gram-positive bacteria. By conjugating this peptide and its analogs with lipophilic phthalocyanine (Pc), we identified a new antibiotic peptide [PcG3K5(RW)3]. The peptide demonstrates increased antimicrobial effect to both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. In addition, Pc also provides added and potent antimicrobial effect upon red light illumination. The inhibitory efficacy of PcG3K5(RW)3 was increased by ~140-fold to nanomolar range upon illumination. Moreover, PcG3K5(RW)3 was safe for mammalian cell and promoted wound healing in the mouse infection model. Our work provides a new direction to optimize antimicrobial peptides to enhance antimicrobial efficacy.


2020 ◽  
Vol 13 (7) ◽  
pp. 3390-3397
Author(s):  
Regina Kemunto Mayaka ◽  
Alice Wanjiku Njue ◽  
Moses Kiprotich Langat ◽  
Peter Kiplagat Cheplogoi ◽  
Josiah Ouma Omolo

The emergence of antibiotic resistant pathogens has continuously increased, leading to a growing worldwide health threat due to infectious diseases. And therefore in our search for antibacterial and antifungal compounds from the polypore Ganoderma adspersum, the dried, ground fruiting bodies of G. adspersum were extracted with methanol and solvent removed in a rotary evaporator. The extract was suspended in distilled water, then partitioned using ethyl acetate solvent to obtain an ethyl acetate extract. The extract was fractionated and purified using column chromatographic method and further purification on sephadex LH20. The chemical structures were determined on the basis of NMR spectroscopic data from 1H and 13C NMR, HSQC, HMBC, 1H-1H COSY, and NOESY experiments. Antimicrobial activity against clinically important bacterial and fungal strains was assessed and zones of inhibition were recorded. Compound (1), ergosta-7,22-dien-3-one weakly inhibited the growth of Gram positive bacteria Streptococcus pneumonia and a fungus Cryptococcus neoformans. Compounds ergosta-7,22-dien-3-ol (2) and ergosta-5,7,22-trien-3-ol (3) also inhibited gram positive Streptococcus pyogenes bacteria.Keywords: Polypores, steroid compounds, antimicrobial activity.


2014 ◽  
Vol 86 (3) ◽  
pp. 1693-1700 ◽  
Author(s):  
Hashem Etayash ◽  
Keren Jiang ◽  
Thomas Thundat ◽  
Kamaljit Kaur

2015 ◽  
Vol 112 (14) ◽  
pp. 4453-4458 ◽  
Author(s):  
Michael B. Harbut ◽  
Catherine Vilchèze ◽  
Xiaozhou Luo ◽  
Mary E. Hensler ◽  
Hui Guo ◽  
...  

Infections caused by antibiotic-resistant bacteria are a rising public health threat and make the identification of new antibiotics a priority. From a cell-based screen for bactericidal compounds againstMycobacterium tuberculosisunder nutrient-deprivation conditions we identified auranofin, an orally bioavailable FDA-approved antirheumatic drug, as having potent bactericidal activities against both replicating and nonreplicatingM. tuberculosis. We also found that auranofin is active against other Gram-positive bacteria, includingBacillus subtilisandEnterococcus faecalis, and drug-sensitive and drug-resistant strains ofEnterococcus faeciumandStaphylococcus aureus. Our biochemical studies showed that auranofin inhibits the bacterial thioredoxin reductase, a protein essential in many Gram-positive bacteria for maintaining the thiol-redox balance and protecting against reactive oxidative species. Auranofin decreases the reducing capacity of target bacteria, thereby sensitizing them to oxidative stress. Finally, auranofin was efficacious in a murine model of methicillin-resistantS. aureusinfection. These results suggest that the thioredoxin-mediated redox cascade of Gram-positive pathogens is a valid target for the development of antibacterial drugs, and that the existing clinical agent auranofin may be repurposed to aid in the treatment of several important antibiotic-resistant pathogens.


2007 ◽  
Vol 60 (3) ◽  
pp. 575-581 ◽  
Author(s):  
Marion Grare ◽  
Maxime Mourer ◽  
Stéphane Fontanay ◽  
Jean-Bernard Regnouf-de-Vains ◽  
Chantal Finance ◽  
...  

Author(s):  
Ammar Almaaytah ◽  
Ahmad Farajallah ◽  
Ahmad Abualhaijaa ◽  
Qosay Al-balas

Current research in the field of antimicrobials is focused on the development of novel antibiotics and antimicrobial agents to counteract the huge dilemma that the human population is mainly facing in regards to the rise of bacterial resistance and biofilm infections. Host Defense peptides (HDPs) are a promising group of molecules for antimicrobial development as they share unique characteristics suitable for antimicrobial activity including their broad spectrum of activity and potency against bacteria. AamAP1 is a novel HDP that was identified through molecular cloning from the venom of the North African scorpion Androctonus amoeruxi. In vitro antimicrobial assays revealed that the peptide displays moderate activity against different strains of Gram-positive and Gram-negative bacteria. Additionally, the peptide proved to be highly hemolytic and displaying significantly high toxicity against mammalian cells. In our study, a novel synthetic peptide analogue named A3 was designed from the naturally occurring scorpion venom host defense peptide. The design strategy depended on modifying the amino acid sequence of the parent peptide in order to increase its net positive charge, percentage helicity and optimize other physico-chemical parameters involved theoretically in HDPs activity. Accordingly, A3 was evaluated for its in vitro antimicrobial and anti-biofilm activity individually and in combination with four different types of conventional antibiotics against clinical isolates of multi-drug resistant (MDR) Gram-positive bacteria. A3 was also evaluated for its cytotoxicity against mammalian cells. A3 displayed potent and selective in vitro antimicrobial activities against a wide range of MDR Gram-positive bacteria. Our results also showed that combining A3 with conventional antibiotics displayed a synergistic mode of action which resulted in decreasing the MIC value for A3 peptide as low as 0.125 µM. These effective concentrations were associated with negligible toxicities on mammalian cells. In conclusion, A3 exhibits enhanced activity and selectivity when compared with the parent natural scorpion venom peptide. The combination of A3 with conventional antibiotics may be pursued as a potential novel treatment strategy against MDR and biofilm forming bacteria.


2021 ◽  
Vol 8 ◽  
Author(s):  
Qun Wang ◽  
Bo Peng ◽  
Mingyue Song ◽  
Abdullah ◽  
Jun Li ◽  
...  

Previous studies from our lab have shown that the antimicrobial peptide F1 obtained from the milk fermentation by Lactobacillus paracasei FX-6 derived from Tibetan kefir was different from common antimicrobial peptides; specifically, F1 simultaneously inhibited the growth of Gram-negative and Gram-positive bacteria. Here, we present follow-on work demonstrating that after the antimicrobial peptide F1 acts on either Escherichia coli ATCC 25922 (E. coli) or Staphylococcus aureus ATCC 63589 (S. aureus), their respective bacterial membranes were severely deformed. This deformation allowed leakage of potassium and magnesium ions from the bacterial membrane. The interaction between the antimicrobial peptide F1 and the bacterial membrane was further explored by artificially simulating the bacterial phospholipid membranes and then extracting them. The study results indicated that after the antimicrobial peptide F1 interacted with the bacterial membranes caused significant calcein leakage that had been simulated by different liposomes. Furthermore, transmission electron microscopy observations revealed that the phospholipid membrane structure was destroyed and the liposomes presented aggregation and precipitation. Quartz Crystal Microbalance with Dissipation (QCM-D) results showed that the antimicrobial peptide F1 significantly reduced the quality of liposome membrane and increased their viscoelasticity. Based on the study's findings, the phospholipid membrane particle size was significantly increased, indicating that the antimicrobial peptide F1 had a direct effect on the phospholipid membrane. Conclusively, the antimicrobial peptide F1 destroyed the membrane structure of both Gram-negative and Gram-positive bacteria by destroying the shared components of their respective phospholipid membranes which resulted in leakage of cell contents and subsequently cell death.


2002 ◽  
Vol 48 (9) ◽  
pp. 810-820 ◽  
Author(s):  
Kelly L MacDonald ◽  
Terry J Beveridge

Previous studies have shown that gentamicin-induced membrane vesicles (g-MVs) from Pseudomonas aeruginosa PAO1 possess both the antibiotic (gentamicin) and a potent peptidoglycan hydrolase (PGase; autolysin) that is effective in killing gram-negative pathogens. This present study evaluated the therapeutic potential of g-MVs against four gram-positive bacteria. Bactericidal assays and electron microscopy of thin sections revealed that Bacillus subtilis 168 and Staphylococcus aureus D2C were susceptible to killing mediated by g-MVs, Listeria monocytogenes ATCC 19113 was slightly susceptible, whereas Enterococcus hirae ATCC 9790 was unaffected. g-MVs were generally more effective against the bacteria than was soluble gentamicin, suggesting they could have more killing power than natural membrane vesicles containing no antibiotic. Electron microscopy and hydrophobic interaction chromatography showed that more membrane vesicles (MVs) initially attached to B. subtilis (hydrophilic) than to predominantly hydrophobic E. hirae, L. monocytogenes, and S. aureus. Zymograms containing murein sacculi as an enzyme substrate illustrated that all organisms except E. hirae were sensitive to the 26-kDa autolysin to varying degrees. Peptidoglycan O-acetylation did not influence susceptibility to MV-mediated lysis. Though not universally effective, the g-MV delivery system remains a promising therapeutic alternative for specific gram-positive infections.Key words: gram-negative membrane vesicles, gentamicin, autolysin.


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