Peptidomic analysis in the discovery of therapeutically valuable peptides in amphibian skin secretions

ABSTRACT

Introduction: The emergence of multidrug-resistant microorganisms has necessitated a search for new antimicrobial agents. Skin secretions of many frog species contain peptides that possess potent, broad-spectrum antibacterial and antifungal activities and so show promise for development into anti-infective agents. Several such peptides also possess cytokine-mediated anti-inflammatory properties and a range of anti-diabetic activities.

Areas covered: A peptidomic approach, involving reversed-phase HPLC and MALDI mass spectrometry, to the comprehensive identification of peptides of potential therapeutic importance in frog skin secretions is described and its advantages over analyses involving bioassays discussed. Peptidomic studies relating to the characterization of peptides with demonstrated antimicrobial, anti-inflammatory and anti-diabetic properties in skin secretions of frogs belonging to the extensive Pipidae and Ranidae families are reviewed.

Expert commentary: The initial promise of frog skin peptides as agents to treat infections produced by drug-resistant microorganisms has not been fulfilled although topical applications to treat skin diseases and a role in promoting wound healing remains a possibility. Future directions are more likely to involve the application of such peptides in the treatment of patients with sepsis and related inflammatory conditions and as a component of a therapeutic regime for Type 2 diabetes.

KEYWORDS:

• Anti-diabetic
• anti-inflammatory
• antimicrobial
• frog skin
• host-defense
• pipide
• Ranidae

Article highlights

• Peptidomic analysis involving RP-HPLC coupled with MALDI-TOF mass spectrometry may be used for the rapid and comprehensive identification of peptides in frog skin secretions.

• The approach has several advantages over methods that use bioassays for detection.

• Host defense peptides with therapeutic potential belonging to the magainin, PGLa, CPF, tigerinin, hymenochirin, and pseudhymenochirin peptide families have been identified by peptidomic analysis in secretions of Pipidae frogs.

• Peptides of therapeutic interest belonging to the esculentin-1, esculentin-2, brevinin-2, temporin, and tigerinin families have been identified by peptidomic analysis in secretions of Ranidae frogs.

• Potential clinical applications include topical treatment of skin infections caused by antibiotic-resistant microorganisms, promotion of wound healing, therapy for sepsis and related inflammatory conditions and treatment of patients with obesity-related Type 2 diabetes mellitus.

Acknowledgments

The authors would like to thank G. John Measey, Stellenbosch University for help with collection and identification of the X. laevis x X. gilli hybrid frog.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.