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A Novel Antimicrobial Drug from an Unlikely Source - The African Clawed Frog

A recent article suggests that the growing problem of antibiotic drug resistance may be addressed with a new drug that mimics our innate immune system - or more specifically, that of the African clawed frog (Xenopus laevis).  The article, published in Clinical Infectious Diseases, describes the clinical efficacy of pexiganan (CAS Registry Number 147664-63-9):

• Lipsky, B.A.; Holroyd, K.J.; Zasloff, M. Topical versus Systemic Antimicrobial Therapy for Treating Mildly Infected Diabetic Foot Ulcers: A Randomized, Controlled, Double-Blinded, Multicenter Trial of Pexiganan Cream. Clin. Infect. Dis. 2008, 47, 1537-1545.

According to the authors, "The results support the potential of topical pexiganan as a therapeutic alternative to an orally-administered antibiotic for treating mildly infected diabetic foot ulcers."  Pexiganan is a synthetic analog of magainin II (CAS Registry Number 108433-95-0), isolated from the skin of the African clawed frog and one of more than 1000 antimicrobial peptides identified in plants and animals.¹  These short peptide substances contribute to an organism's innate immunity - that is, its natural ability to ward off microbial infection.

The idea of looking to the innate immune system for novel antimicrobial drugs isn't new.  In fact, prior to his famous 1929 report on a "contaminating mould,"² Alexander Fleming published a much less celebrated article on his discovery of lysozyme, "a remarkable bacteriolytic element found in tissues and secretions."³  However, it was decades before scientists began to fully realize the therapeutic potential of substances that contribute to the innate immune system.

In 1987, Michael Zasloff isolated and characterized antimicrobial peptide "magainins" from the skin of the African clawed frog after he noted that surgical wounds on the frogs rarely became infected:

• "These peptides may be responsible for the extraordinary freedom from infection characteristic of wound healing in this animal and appear to constitute a previously unrecognized antimicrobial host-defense system."⁴ 

This important observation not only led to the development of pexiganan but also paved the way for many other scientists who now look to the innate immune system to guide the design of novel antimicrobial drugs.

You can use SciFinder or STN to search the CAS databases for additional information about Xenopus laevis, pexiganan, magainins, and antimicrobial peptides.  If your organization is enabled to use the web version of SciFinder, you can directly access details for the substances and references listed in this article.

For additional information about antibiotic drug resistance, see the ACS Global Challenges/Chemistry Solutions podcast, Promoting Public Health.

Contributed by
Peter S. Carlton, Ph.D.
CAS Communications

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References

1. The Antimicrobial Peptide Database. http://aps.unmc.edu/AP/main.php (accessed Dec 22, 2008).
2. Fleming, A. The Antibacterial Action of Cultures of a Penicillium, with Special Reference to Their Use in the Isolation of B. influenzae. Br. J. Exp. Pathol. 1929, 10, 226-236.
3. Fleming, A. Remarkable Bacteriolytic Element Found in Tissues and Secretions. Proc. R. Soc. Lond., B 1922, 93, 306-317.
4. Zasloff, M. Magainins, A Class of Antimicrobial Peptides from Xenopus Skin: Isolation, Characterization of Two Active Forms, and Partial cDNA Sequence of a Precursor. Proc. Natl. Acad. Sci. USA 1987, 84, 5449-5453.

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