Potential of immunomodulatory host defense peptides as novel anti-infectives

Easton, Donna M.; Nijnik, Anastasia; Mayer, Matthew L.; Hancock, Robert E. W.

doi:10.1016/j.tibtech.2009.07.004

Cited by 187 publications

(169 citation statements)

References 80 publications

(100 reference statements)

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“…Their diverse action modes include disruption of membrane integrity, impairment of nucleic acid and protein synthesis, inhibition of chaperone-assisted protein folding, interruption of cell-wall biosynthesis pathway, and even targeting of membrane biogenesis (2)(3)(4). Some vertebrate AMPs (e.g., human cathelicidins and defensins) have also evolved a multifunctional, immunomodulatory ability in bridging the innate and adaptive immune systems (5).…”

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confidence: 99%

Dermatophytic defensin with antiinfective potential

Zhu

Gao

Harvey

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Fungi are a newly emerging source of peptide antibiotics with therapeutic potential. Here, we report 17 new fungal defensin-like peptide (fDLP) genes and the detailed characterization of a corresponding synthetic fDLP (micasin) from a dermatophyte in terms of its structure, activity and therapeutic potential. NMR analysis showed that synthetic micasin adopts a "hallmark" cysteinestablized α-helical and β-sheet fold. It was active on both Grampositive and Gram-negtive bacteria, and importantly it killed two clinical isolates of methicillin-resistant Staphylococcus aureus and the opportunistic pathogen Pseudomonas aeruginosa at low micromolar concentrations. Micasin killed approximately 100% of treated bacteria within 3 h through a membrane nondisruptive mechanism of action, and showed extremely low hemolysis and high serum stability. Consistent with these functional properties, micasin increases survival in mice infected by the pathogenic bacteria in a peritonitis model. Our work represents a valuable approach to explore novel peptide antibiotics from a large resource of fungal genomes.ascomycota | methicillin-resistant Staphylococcus aureus | plectasin | mouse peritonitis model

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mentioning

confidence: 99%

Dermatophytic defensin with antiinfective potential

Zhu

Gao

Harvey

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…More than 1000 different antimicrobial peptides have been documented with activity against viruses, bacteria, and fungi, prompting interest in using the structural principles of small cationic, amphiphilic molecules for improving and fine tuning target specificity and efficacy (3)(4)(5)(6). Non-natural multivalent AMPs have been designed by conjugating copies of a peptide monomer to scaffold molecules via naturally occurring intermolecular disulfide bridges or unnatural scaffold linkers (7).…”

mentioning

confidence: 99%

Progressive Structuring of a Branched Antimicrobial Peptide on the Path to the Inner Membrane Target

Bai

Liu

et al. 2012

Journal of Biological Chemistry

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Background: A cationic branched peptide was designed with antimicrobial activities against Gram-negative bacteria. Results: B2088 penetrated the outer membrane through inducing phase transitions of LPS and caused inner membrane depolarization by lipid redistribution. Conclusion: Our findings support the interfacial activity model and extend it to more complex interfaces. Significance: We provide a functional structural motif for developing new antimicrobials.

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“…Understanding of the strong immunomodulator properties of antimicrobial peptides led to the development of a new drug class called "innate defense regulators," which are synthetic analogs of these peptides (32). Phase 2 and phase 3 clinical studies of at least 11 of these drugs, which are greatly promising, are ongoing (32).…”

Section: Tssmentioning

confidence: 99%

“…Phase 2 and phase 3 clinical studies of at least 11 of these drugs, which are greatly promising, are ongoing (32). As the roles of antimicrobial peptides in the pathogenesis of allergic diseases become clearer, studies related with the use of this new drug group in AR and other allergic diseases will probably come to the fore in the near future.…”

Section: Tssmentioning

confidence: 99%

Evaluation of nasal fluid β-defensin 2 levels in children with allergic rhinitis

et al. 2017

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Aim: Knowledge about the role of the innate immune system in the pathogenesis of allergic diseases has been expanding in recent years. Defensins are antimicrobial peptides that are components of the innate immune system. Defensins have strong efficacy against bacterial, viral, and fungal infections. Moreover, they have regulatory functions in many physiologic processes such as antitumoral immunity, chemotaxis, inflammation, and wound healing. In this study, we aimed to investigate β-defensin 2 levels in the nasal fluids of children with allergic rhinitis. Material and Methods:Study and control groups consisted of 28 patients with newly diagnosed allergic rhinitis who were not taking any medication, and 23 healthy children. Skin prick tests were performed on patients with allergic rhinitis and disease severity was assessed using the total symptom score. Nasal fluid samples were obtained using a modified polyurethane sponge absorption method from patients and control subjects. Nasal fluid β-defensin 2 levels were determined using an enzyme-linked immunosorbent assay (ELISA). Results:The median value of nasal fluid β-defensin 2 levels were 173.8 pg/mL (interquartile range; 54.8-205.9 pg/mL) in allergic rhinitis group and 241.6 pg/mL (163.5-315.2 pg/mL) in the control group. There was a statistically significant difference between the two groups (p=0.01). Moreover, nasal fluid β-defensin 2 levels showed a significant negative correlation with total symptom scores (rho= -0.78, p<0.001). Conclusions:Children with allergic rhinitis have reduced nasal fluid β-defensin 2 levels compared with controls, and β-defensin 2 levels were negatively correlated with disease severity. A more definite understanding of the roles of defensins and other antimicrobial peptides in allergic inflammation can open up new horizons in the management and treatment of these common diseases. (Turk Pediatri Ars 2017; 52: 79-84)

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Potential of immunomodulatory host defense peptides as novel anti-infectives

Cited by 187 publications

References 80 publications

Dermatophytic defensin with antiinfective potential

Dermatophytic defensin with antiinfective potential

Progressive Structuring of a Branched Antimicrobial Peptide on the Path to the Inner Membrane Target

Evaluation of nasal fluid β-defensin 2 levels in children with allergic rhinitis

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