Are antibiotics really only made by bacteria and fungi?

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Sandra Porter

After reading Kevin C.'s question in the comments on my last antibiotic post, I decided to look into this question a bit further.

As far as I can tell, most of the commercially producted antibiotics are made by bacteria, fungi, and a bit chemistry (more on that in a moment). It appears, however, that compounds with antimicrobial properties are made by just about everything. Just to make things complicated, these molecules are sometimes called "antibiotics" in the literature and sometimes they're not.

Many of the molecules with antimicrobial activity are short peptides- chains of amino acids between 10 and 50 residues long (1, 2). Others are lipids (3).

Oxylipins
Plants make a large, diverse, family of compounds called "oxylipins" that are derived from polyunsaturated fatty acids. Researchers became interested in these compounds after learning that they were produced in response to plant pathogens. The idea was that they might be part of a plant immune response. Prost, et. al. tested 43 different oxylipins in the article cited below (3) and found that most of them were able to hinder growth of some kinds of pathogens. How these compounds work isn't yet known, but they seem to have some specificity. Some oxylipins were better at inhibiting fungi. Some were better at inhibiting the growth of bacterial pathogens, like Pseudomonas syringae.

i-8eceff1c8a44723923ddc6308a43406a-magainin.gifAntimicrobial peptides
The antimicrobial peptides are a much better characterized group of compounds. They have diverse structures and sequences. Some act against bacteria and some against fungi. And they are made by just about everything including amphibians, mammals, plants, and insects. Even Drosophila (fruit flies) make an antifungal peptide called drosomycin. Magainin, an antimicrobial peptide from frog skin, is shown in the image.

Tongue piercing
I remember first learning about these peptides a long time ago. One day, one of my immunology students came into class with his tongue pierced. I was aghast and well, really worried about the potential for infection. Sure, students at my community college were well known to pierce every part of their bodies that could be pierced, but this was someone that I knew. And you've probably heard the old line about a dog's mouth being cleaner than a human's. I didn't really believe that that was true, but to me, putting a hole in your tongue is just plain unhygienic. This student surprised me though, he brought in an article about antimicrobial peptides in cow tongues and used that for his oral presentation. He was the first person to tell me that antimicrobial peptides were made in the tongue.

Commercial development of antimicrobial peptides
Now, according to the Nature Biotechnology article (2), four antimicrobial peptides have been tested in phase 3 clinical trials. Only two of them were effective: Pexiganan, for treating diabetic foot ulcers, and Omiganan for preventing catheter-associated infections. Neither one has been approved by the FDA, but many other antimicrobial peptides are in the pipeline).

How quickly will bacteria become resistant?
One intriguing aspect of these compounds, is the question of resistance. The bacteria that make antibiotics also possess genes that make them resistant to antibiotics. Those genes can be shared with other bacteria. These antimicrobial peptides, however, are not accompanied by bacterial antibiotic resistance genes, so it might take more time for bacterial populations to develop resistance to these peptides.

Time will tell.

References:
1. Micheal Zasloff. 2002. "Antimicrobial peptides of multicellular organisms." Nature 415:389-395.

2. Robert E W Hancock & Hans-Georg Sahl. 2006. "Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies" Nature Biotechnology - 24:1551 - 1557.

3. Prost, I., et.al. 2005. "Evaluation of the Antimicrobial Activities of Plant Oxylipins Supports Their Involvement in Defense against Pathogens."
Plant Physiol. 139(4): 1902-1913.