Positional scanning library applied to the human eosinophil cationic protein/RNase3 N-terminus reveals novel and potent anti-biofilm peptides

Pulido, David; Prats-Ejarque, Guillem; Villalba, Clara; Albacar, Marcel; Moussaoui, Mohammed; Andreu, David; Volkmer, Rudolf; Torrent, M. C.; Boix, Ester

doi:10.1016/j.ejmech.2018.05.012

Cited by 16 publications

(22 citation statements)

References 49 publications

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“…Positional scanning libraries have large diversity, but often do not yield specific recognition peptides, presumably due to a large flexibility of the peptides. However, such libraries have been used to identify a range of protease substrates and protease inhibitors as well as optimal B and T cell epitopes [167][168][169][170][171]. One advantage of such libraries is that D-amino acids, non-natural amino acids, or other types of molecules, e.g., PTMs, can fairly easily be incorporated, which sometimes yields peptides with improved properties [167,172].…”

Section: Peptide Librariesmentioning

confidence: 99%

Peptides, Antibodies, Peptide Antibodies and More

Trier

Hansen

Houen

2019

IJMS

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The applications of peptides and antibodies to multiple targets have emerged as powerful tools in research, diagnostics, vaccine development, and therapeutics. Antibodies are unique since they, in theory, can be directed to any desired target, which illustrates their versatile nature and broad spectrum of use as illustrated by numerous applications of peptide antibodies. In recent years, due to the inherent limitations such as size and physical properties of antibodies, it has been attempted to generate new molecular compounds with equally high specificity and affinity, albeit with relatively low success. Based on this, peptides, antibodies, and peptide antibodies have established their importance and remain crucial reagents in molecular biology.

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Section: Peptide Librariesmentioning

confidence: 99%

Peptides, Antibodies, Peptide Antibodies and More

Trier

Hansen

Houen

2019

IJMS

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“…Cytotoxicity was measured for the MRC-5 and HepG2 human cell lines using the MTT assay, as described previously (Pulido et al, 2018). Cells were grown in 5% CO 2 at 37 °C with minimal essential medium supplemented with 10% fetal bovine serum (FBS).…”

Section: Methodsmentioning

confidence: 99%

Testing a Human Antimicrobial RNase Chimera Against Bacterial Resistance

Prats-Ejarque

Ait-Ichou

et al. 2019

Front. Microbiol.

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The emergence of bacterial resistance to the most commonly used antibiotics encourages the design of novel antimicrobial drugs. Antimicrobial proteins and peptides (AMPs) are the key players in host innate immunity. They exert a rapid and multifaceted action that reduces the development of bacterial adaptation mechanisms. Human antimicrobial RNases belonging to the vertebrate specific RNase A superfamily participate in the maintenance of tissue and body fluid sterility. Among the eight human canonical RNases, RNase 3 stands out as the most cationic and effective bactericidal protein against Gram-negative species. Its enhanced ability to disrupt the bacterial cell wall has evolved in detriment of its catalytic activity. Based on structure-functional studies we have designed an RNase 3/1 hybrid construct that combines the high catalytic activity of RNase 1 with RNase 3 bactericidal properties. Next, we have explored the ability of this hybrid RNase to target the development of bacterial resistance on an Acinetobacter baumannii cell culture. Synergy assays were performed in combination with colistin, a standard antimicrobial peptide used as an antibiotic to treat severe infections. Positive synergism was observed between colistin and the RNase 3/1 hybrid protein. Subsequently, using an in vitro experimental evolution assay, by exposure of a bacterial culture to colistin at incremental doses, we demonstrated the ability of the RNase 3/1 construct to reduce the emergence of bacterial antimicrobial resistance. The results advance the potential applicability of RNase-based drugs as antibiotic adjuvants.

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“…Regarding antimicrobial activity, RNase 3 stands out for its high bactericidal action and the efficacy of an N-terminus-derived peptide on Gram-negative bacteria biofilms. This ability to remove biofilms of Gram-negative species can be explained by its specific cell agglutination and lipopolysaccharide-binding properties [ 12 , 13 , 14 , 15 ]. Besides, RNase 3 was proved effective against macrophage intracellular infection.…”

Section: Introductionmentioning

confidence: 99%

“…In this context, we designed an RNase 3/1 hybrid that combines the unique features of RNase 3 and the high catalytic activity and ribonuclease inhibitor affinity of RNase 1 and tested the construct in an in vitro experimental evolution test with Acinetobacter baumannii , where it demonstrated its ability to delay the acquisition of colistin resistance [ 15 ]. Antimicrobial RNases have been reported to be effective against biofilm-forming pathogens, such as Mycobacterium tuberculosis , A. baumannii , or Pseudomonas aeruginosa [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Magnetite Nanoparticles Functionalized with RNases against Intracellular Infection of Pseudomonas aeruginosa

et al. 2020

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Current treatments against bacterial infections have severe limitations, mainly due to the emergence of resistance to conventional antibiotics. In the specific case of Pseudomonas aeruginosa strains, they have shown a number of resistance mechanisms to counter most antibiotics. Human secretory RNases from the RNase A superfamily are proteins involved in a wide variety of biological functions, including antimicrobial activity. The objective of this work was to explore the intracellular antimicrobial action of an RNase 3/1 hybrid protein that combines RNase 1 high catalytic and RNase 3 bactericidal activities. To achieve this, we immobilized the RNase 3/1 hybrid on Polyetheramine (PEA)-modified magnetite nanoparticles (MNPs). The obtained nanobioconjugates were tested in macrophage-derived THP-1 cells infected with Pseudomonas aeruginosa PAO1. The obtained results show high antimicrobial activity of the functionalized hybrid protein (MNP-RNase 3/1) against the intracellular growth of P. aeruginosa of the functionalized hybrid protein. Moreover, the immobilization of RNase 3/1 enhances its antimicrobial and cell-penetrating activities without generating any significant cell damage. Considering the observed antibacterial activity, the immobilization of the RNase A superfamily and derived proteins represents an innovative approach for the development of new strategies using nanoparticles to deliver antimicrobials that counteract P. aeruginosa intracellular infection.

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Positional scanning library applied to the human eosinophil cationic protein/RNase3 N-terminus reveals novel and potent anti-biofilm peptides

Cited by 16 publications

References 49 publications

Peptides, Antibodies, Peptide Antibodies and More

Peptides, Antibodies, Peptide Antibodies and More

Testing a Human Antimicrobial RNase Chimera Against Bacterial Resistance

Magnetite Nanoparticles Functionalized with RNases against Intracellular Infection of Pseudomonas aeruginosa

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