Protein post‐translational modification in host defense: the antimicrobial mechanism of action of human eosinophil cationic protein native forms

Salazar, Vivian A.; Rubin, Jenny; Moussaoui, Mohammed; Pulido, David; Nogués, M. Victòria; Venge, Per; Boix, Ester

doi:10.1111/febs.13082

Cited by 19 publications

(16 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MBC of each peptide was determined as described previously [69,70]. Bacteria were incubated at 37 °C overnight in Luria-Bertani broth (LB) and diluted to approximately 5 × 10 5 CFU/mL.…”

Section: Methodsmentioning

confidence: 99%

Unveiling the Multifaceted Mechanisms of Antibacterial Activity of Buforin II and Frenatin 2.3S Peptides from Skin Micro-Organs of the Orinoco Lime Treefrog (Sphaenorhynchus lacteus)

Muñoz-Camargo

Salazar

Barrero-Guevara

et al. 2018

IJMS

Self Cite

View full text Add to dashboard Cite

Amphibian skin is a rich source of natural compounds with diverse antimicrobial and immune defense properties. Our previous studies showed that the frog skin secretions obtained by skin micro-organs from various species of Colombian anurans have antimicrobial activities against bacteria and viruses. We purified for the first time two antimicrobial peptides from the skin micro-organs of the Orinoco lime treefrog (Sphaenorhynchus lacteus) that correspond to Buforin II (BF2) and Frenatin 2.3S (F2.3S). Here, we have synthesized the two peptides and tested them against Gram-negative and Gram-positive bacteria, observing an effective bactericidal activity at micromolar concentrations. Evaluation of BF2 and F2.3S membrane destabilization activity on bacterial cell cultures and synthetic lipid bilayers reveals a distinct membrane interaction mechanism. BF2 agglutinates E. coli cells and synthetic vesicles, whereas F2.3S shows a high depolarization and membrane destabilization activities. Interestingly, we found that F2.3S is able to internalize within bacterial cells and can bind nucleic acids, as previously reported for BF2. Moreover, bacterial exposure to both peptides alters the expression profile of genes related to stress and resistance response. Overall, these results show the multifaceted mechanism of action of both antimicrobial peptides that can provide alternative tools in the fight against bacterial resistance.

show abstract

Section: Methodsmentioning

confidence: 99%

Unveiling the Multifaceted Mechanisms of Antibacterial Activity of Buforin II and Frenatin 2.3S Peptides from Skin Micro-Organs of the Orinoco Lime Treefrog (Sphaenorhynchus lacteus)

Muñoz-Camargo

Salazar

Barrero-Guevara

et al. 2018

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Antimicrobial activity was calculated as the minimum bactericidal concentration (MBC), defined as the lowest protein/peptide concentration that completely eradicated microbial growth. The MBC of each protein/peptide was determined as described previously (27,34). Bacteria were incubated at 37°C overnight in Luria-Bertani broth (LB) and diluted to approximately 5 ϫ 10 5 CFU/ml.…”

Section: Methodsmentioning

confidence: 99%

A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities

Pulido

Prats-Ejarque

Villalba

et al. 2016

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

bEradication of established biofilm communities of pathogenic Gram-negative species is one of the pending challenges for the development of new antimicrobial agents. In particular, Pseudomonas aeruginosa is one of the main dreaded nosocomial species, with a tendency to form organized microbial communities that offer an enhanced resistance to conventional antibiotics. We describe here an engineered antimicrobial peptide (AMP) which combines bactericidal activity with a high bacterial cell agglutination and lipopolysaccharide (LPS) affinity. The RN3(5-17P22-36) peptide is a 30-mer derived from the eosinophil cationic protein (ECP), a host defense RNase secreted by eosinophils upon infection, with a wide spectrum of antipathogen activity. The protein displays high biofilm eradication activity that is not dependent on its RNase catalytic activity, as evaluated by using an active site-defective mutant. On the other hand, the peptide encompasses both the LPS-binding and aggregation-prone regions from the parental protein, which provide the appropriate structural features for the peptide's attachment to the bacterial exopolysaccharide layer and further improved removal of established biofilms. Moreover, the peptide's high cationicity and amphipathicity promote the cell membrane destabilization action. The results are also compared side by side with other reported AMPs effective against either planktonic and/or biofilm forms of Pseudomonas aeruginosa strain PAO1. The ECP and its derived peptide are unique in combining high bactericidal potency and cell agglutination activity, achieving effective biofilm eradication at a low micromolar range. We conclude that the designed RN3(5-17P22-36) peptide is a promising lead candidate against Gram-negative biofilms.

show abstract

“…For example, phosphorylation of CA/P24 could affect the HIV reverse transcription process (Chen et al, 2018a;. Glycosylation of ECP (the human eosinophil cationic protein) regulates its antimicrobial ability (Salazar et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

The phosphorylation of the N protein could affect PRRSV virulence in vivo

Yao

et al. 2019

Veterinary Microbiology

View full text Add to dashboard Cite

A B S T R A C TThe porcine respiratory and reproductive syndrome virus (PRRSV) nucleocapsid (N) protein is a multiphosphorylated protein.It has been proved that the phosphorylation of N protein could regulate the growth ability of PRRSV in Marc-145 cells. However, further investigation is needed to determine whether phosphorylation of the N protein could affect PRRSV virulence in piglets. In this study, we confirmed that the mutations could impair PRRSV replication ability in porcine primary macrophages (PAMs) as they did in Marc-145 cells. The animal experiments suggested that the pathogenicity of the mutated virus (A105-120) was significantly reduced compared with parent strain (XH-GD). Our results suggested that the phosphorylation of the N protein contributes to virus replication and virulence. This study is the first to identify a specific modification involved in PRRSV pathogenicity. Mutation of PTMs sites is also a novel way to attenuate PRRSV virulence. The mutations could be a marker in a vaccine. In conclusion, our study will improve our understanding of the molecular mechanisms of PRRSV pathogenicity.

show abstract

Protein post‐translational modification in host defense: the antimicrobial mechanism of action of human eosinophil cationic protein native forms

Cited by 19 publications

References 70 publications

Unveiling the Multifaceted Mechanisms of Antibacterial Activity of Buforin II and Frenatin 2.3S Peptides from Skin Micro-Organs of the Orinoco Lime Treefrog (Sphaenorhynchus lacteus)

Unveiling the Multifaceted Mechanisms of Antibacterial Activity of Buforin II and Frenatin 2.3S Peptides from Skin Micro-Organs of the Orinoco Lime Treefrog (Sphaenorhynchus lacteus)

A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities

The phosphorylation of the N protein could affect PRRSV virulence in vivo

Contact Info

Product

Resources

About