Isolation and characterization of elasnin, a new human granulocyte elastase inhibitor produced by a strain of Streptomyces.

Biofilm is made by microbes and often offers protection by making them more tolerant, resistant, and resilient to wide-range antimicrobials. Biofilm-related infections account for more than 80% of human bacterial infections and are especially prevalent in chronic tissue and device-related infections. Owing to the great challenge in treating biofilms, novel and effective antibiofilm compounds urgently need to be identified. We herein identified elasnin as a potent biofilm-targeting compound against methicillin-resistant Staphylococcus aureus (MRSA) through bioassay-guided isolation of bioactive compounds from Actinobacteria. Elasnin effectively inhibited biofilm formation and eradicated pre-formed biofilms of MRSA, and it displays low cytotoxicity with a low risk of resistance development. Transcriptomic and proteomic analyses combined with confocal microscopy observation revealed that elasnin destroyed the biofilm matrix in a time-dependent manner and interfered with cell cycle during the exponential phase, primarily by repressing the expression of virulence factors. Moreover, the biofilm cells released from elasnin treatment showed increased sensitivity to penicillin G. Overall, this study identified elasnin as a promising biofilm-eradicating compound against MRSA and shed light on its action mechanism.

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“…Elasnin further exhibited low cytotoxicity towards different cell lines, consistent with a previous study 50 .…”

Section: Discussionsupporting

confidence: 91%

Mode of action of Elasnin as biofilm-formation eradicator of Methicillin-Resistant Staphylococcus aureus

Long

Sulaiman

Xiao

et al. 2021

Preprint

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“…It is also capable to inhibit trypsin and cathepsin B. S.hygroscopicus and S.lavendulae produced chymostatin against chymotrypsin. S.griseoruber produced elastatinal against elastase [27], [28]. So far, only few reports only available for anti- Pf activity of marine actinobacteria.…”

Section: Resultsmentioning

confidence: 99%

Protease Inhibitors from Marine Actinobacteria as a Potential Source for Antimalarial Compound

et al. 2014

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The study was planned to screen the marine actinobacterial extract for the protease inhibitor activity and its anti- Pf activity under in vitro and in vivo conditions. Out of 100 isolates, only 3 isolates exhibited moderate to high protease inhibitor activities on trypsin, chymotrypsin and proteinase K. Based on protease inhibitor activity 3 isolates were chosen for further studies. The potential isolate was characterized by polyphasic approach and identified as Streptomyces sp LK3 (JF710608). The lead compound was identified as peptide from Streptomyces sp LK3. The double-reciprocal plot displayed inhibition mode is non-competitive and it confirms the irreversible nature of protease inhibitor. The peptide from Streptomyces sp LK3 extract showed significant anti plasmodial activity (IC50: 25.78 µg/ml). In in vivo model, the highest level of parasitemia suppression (≈45%) was observed in 600 mg/kg of the peptide. These analyses revealed no significant changes were observed in the spleen and liver tissue during 8 dpi. The results confirmed up-regulation of TGF-β and down regulation of TNF-α in tissue and serum level in PbA infected peptide treated mice compared to PbA infection. The results obtained infer that the peptide possesses anti- Pf activity activity. It suggests that the extracts have novel metabolites and could be considered as a potential source for drug development.

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“…Unlike vancomycin, which exclusively targets essential life processes and kills the pathogen, elasnin did not affect the cell viability and thus holds great potential in delaying resistance. Elasnin was first discovered in 1978 as a new elastase inhibitor with low toxicity in mice and high selectivity to human granulocyte elastase 22 . The low toxicity, biofilm-specific activity and selectivity of elasnin may make it a new alternative for treating biofilm-associated infections of Gram-positive bacteria, which prevents the development of antibiotic resistance.…”

Section: Discussionmentioning

confidence: 99%

A potent antibiofilm agent inhibits and eradicates mono- and multi-species biofilms

Long

Wang

Chiang

et al. 2020

Preprint

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18Biofilms are surface-attached multicellular communities that create many problems in 19 human health and various industries. Given the prominence of biofilms in biofouling 20 and infectious diseases, antibiofilm control approaches are highly sought after. In the 21 present study, we identified elasnin as a potent antibiofilm agent through a bioassay-22 guided approach. Elasnin specifically inhibited the biofilm formation of bacterial 23 mono-species and eradicated the mature biofilm of Gram-positive bacteria at 24 concentrations below 2.5 μg/mL with a low toxic effect on cells and a low resistance 25 risk. Confocal observations illustrated that elasnin decreased cell aggregations and 26 destroyed the biofilm matrix. Furthermore, elasnin-based antibiofilm coatings were 27 prepared and inhibited the formation of multi-species biofilms and the attachment of 28 large biofouling organisms in the field test. These findings suggest that elasnin is a 29 promising antibiofilm agent for future applications in biofilm control. 30 31 Importance 32 Due to the increased diversity of biofilm-associated infections and the failure of 33 conventional antimicrobial treatment, new and effective biofilm-specific 34 pharmacologic strategies are urgently needed. Elasnin is a new antibiofilm natural 35 product produced by Streptomyces with high efficiency and low toxicity. Elasnin 36 effectively destroyed the biofilm matrix of Gram-positive bacteria, thus making them 37 more susceptible to antibiotics. Unlike currently deployed antibiotic vancomycin, 38 which exclusively targets essential life processes and kills the pathogen, elasnin did not 39 3 exhibit bactericidal effect and thus held great potential in delaying resistance. With high 40 yield, elasnin-based coatings were easily prepared with low expenditures and exhibited 41 favorable performance in field test. Collectively, the antibiofilm properties of elasnin, 42 combined with the low cost of supply and the low risk of resistance, could provide the 43 basis for the development of a novel antibiofilm agent that could help fight to antibiotics 44 resistance. 45 46 A biofilm is a microorganism community attached to a surface 1 . It consists of 49 microbial cells massed in the matrix of extracellular polymeric substances (EPS), which 50 contain a large variety of biopolymers such as proteins, nucleic acids, lipids, and other 51 substances 2 . Biofilms can be made up of a single microbial species or multiple species 52 that colonize biotic or abiotic surfaces 3,4 . The elaborate biofilm architecture provides a 53shield to the microbes in biofilms and offers them the spatial proximity and internal 54 homeostasis needed for growth and differentiation 3-5 . This makes microbial cells much 55 more resistant than their planktonic counterparts to diverse external insults such as 56 antimicrobial treatment, poisons, protozoans, and host immunity 6,7 . For example, 57 biofilms can render organisms 10-to 1000-fold less susceptible to antimicrobial agents; 58 furthermore, organisms in mult...

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Isolation and characterization of elasnin, a new human granulocyte elastase inhibitor produced by a strain of Streptomyces.

Cited by 40 publications

References 13 publications

Mode of action of Elasnin as biofilm-formation eradicator of Methicillin-Resistant Staphylococcus aureus

Mode of action of Elasnin as biofilm-formation eradicator of Methicillin-Resistant Staphylococcus aureus

Protease Inhibitors from Marine Actinobacteria as a Potential Source for Antimalarial Compound

A potent antibiofilm agent inhibits and eradicates mono- and multi-species biofilms

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