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[SANET-MG] antimicrobial peptides
The Independent Science Panel
Promotion of Science for the Public Good http://www.indsp.org
General Enquiries info@indsp.org Website/Mailing List info@indsp.org
The article below has been submitted on behalf of the Independent
Science Panel to the Niigata Prefecture in Japan, in support of legal
action taken by 12 Japanese citizens seeking to halt the trial of
transgenic rice producing antimicrobial peptides. Please circulate
widely and send to your elected representatives.
Submit it also to the US Environmental Protection Agency and demand
comprehensive risk assessment for transgenic plants producing another
antimicrobial peptide that have been widely field-tested and may be
poised for deregulation.
No to Releases of Transgenic Plants with Antimicrobial Peptides
Professor Joe Cummins and Dr. Mae-Wan Ho
Anti-microbial peptides provide the first line of defence against
invading microbes in both plants and animals. The peptides are involved
in innate immunity, and are 15 to 40 amino acids in length, most of them
hydrophobic (water-hating) and cationic (positively charged). They
provide protection from bacteria, fungi and viruses, acting mainly at
the cell membrane of pathogens [1,2]. The peptides are beginning to be
employed in medicine and in crop protection.
A synthetic peptide D4E1 based on the cecropin B peptide toxin (obtained
from the moth, Cecropia ), consists of a linear sequence of 17 amino
acids: FKLRAKIKVRLRAKIKL (F for phenylalanine, K for lysine, L for
leucine, R for arginine, A for alanine, I for isoleucine, V for valine).
The peptide protected against Aspergillus and Fusarium fungi. It acted
by binding to ergosterol, a sterol present in fungal cell walls [3]. On
further tests, D4E1 was found to have broad- spectrum antimicrobial
action, and was active against fungi belonging to the orders Ascomycete,
Basidiomycete, Deuteromycete and Oomycetes, as well as bacterial
pathogens Psuedomonas and Xanthomonas [4]. The D4E1 toxin also proved
effective in the treatment of human Chlamydia infection [5].
Transgenic tobacco plants transformed with a gene for the peptide D4E1
(driven by a double CaMV promoter and terminated by the nos
transcription terminator, accompanied by a kanamycin resistance marker )
was resistant to fungal pathogens [6]. Poplar trees transformed as in
the transgenic tobacco was resistant to bacterial pathogens A.
tumefacians and X. populi but not to the fungal pathogen Hypoxylon
mammatum [7]. Cotton plants transformed similarly with the gene coding
for D4E1 showed resistance to fungi including Fusarium , Verticillium
and Aspergillus , hence the synthetic peptide was proposed to be
effective against mycotoxin-causing fungal pathogens [8].
Field tests have been conducted on D4E1 transgenic plants in the United
States, transgenic cotton in Arizona and California, and transgenic
potatoes in Idaho [9]. It seems inevitable that petitions to remove the
transgenic crops containing D4E1 from regulation are not far off. As the
D4E1 gene and its peptide product are both fully synthetic, it will be a
stretch to assume that the product is “substantially equivalent” to the
natural product.
Meanwhile, researchers at the National Agricultural Research Center,
Niigata, in Japan have created transgenic rice with genes of the
antimicrobial peptide, defensin, from Brassica . The transgenic rice
plants were resistant to rice blast disease caused by the fungus
Magnaporthe grisea . The researchers went a step further and
systematically altered the genetic code for defensin to produce
synthetic peptides that were far more toxic to the fungus than the
natural peptides [10]. Rice with the synthetic genes and peptides are
being proposed for field-testing prior to commercial release in Japan,
and little effort appears to have been devoted to evaluate the safety
for human health and the environment.
We agree with microbiologist Dr. Takahiro Kanagawa, a senior scientist
at one of Japan's leading research institutes that releases of
transgenic plants containing anti-microbial peptides are dangerous [11].
Defensins and other peptides are, for plants and animals, their first
defence against pathogens. Just as D4E1 was effective against Clamydia
infections [5], alpha-defensins, identified in long- term nonprogressors
with HIV-1 infection [12], may well have applications in preventing AIDS
disease.
The danger highlighted by Dr. Kanagawa is that environmental releases of
these antimicrobial peptides will lead to the evolution of resistance
among microbial pathogens. As Dr. Kanagawa points out, there is already
a report of yeast evolving resistance to defensin from Dahlia after two
days of co- cultivation [13].
The evolution of resistance to antimicrobial peptides will severely
compromise both the natural defence of the human immune system against
disease and the possibilities of effective therapies emerging in the
wake of the disaster of widespread antibiotic resistance. As versions of
the peptides also provide defence against pathogens in other animals and
plants, the ecological impact of resistant pathogens could be devastating.
Another factor adding to the hazards to health and the environment is
that the synthetic transgenes code for peptides that are significantly
different from the natural versions. This may itself be responsible for
toxic or other harmful effects that cannot be known unless thoroughly
tested.
References
1. Bulet P, Stocklin R. and Menin L. Anti-microbial peptides: from
invertebrates to vertebrates Immunol Rev. 2004 ,198,169-84,
2. Boman, H. Antibacterial peptides: basic facts and emerging concepts.
J Intern Med. 2003, 254(3), 197-215.
3. De Lucca AJ, Bland JM, Grimm C, Jacks TJ, Cary JW, Jaynes JM,
Cleveland TE and Walsh TJ. Fungicidal properties, sterol binding, and
proteolytic resistance of the synthetic peptide D4E1. Can J Microbiol.
1998, 44, 514-20.
4. Rajasekaran K, Stromberg KD, Cary JW and Cleveland TE. Broad-spectrum
antimicrobial activity in vitro of the synthetic peptide D4E1. J Agric
Food Chem. 2001, 49, 2799-803.
5. Ballweber LM, Jaynes JE, Stamm WE and Lampe MF. In vitro microbicidal
activities of cecropin peptides D2A21 and D4E1 and gel formulations
containing 0.1 to 2% D2A21 against Chlamydia trachomatis. Antimicrob
Agents Chemother . 2002, 46, 34-41.
6. Cary JW, Rajasekaran1 K, Jaynes JM and Cleveland TE. Transgenic
expression of a gene encoding a synthetic antimicrobial peptide results
in inhibition of fungal growth in vitro and in planta. Plant Sci. 2000,
29,154,171-181.
7. Mentag R, Luckevich M, Morency MJ and Seguin A. Bacterial disease
resistance of transgenic hybrid poplar expressing the synthetic
antimicrobial peptide D4E1. Tree Physiol. 2003, 23,405-11.
8. Rajaskaran K, Cary J, Jaynes J. and Clevland T. Disease resistance
conferred by the expression of a gene encoding a synthetic peptide in
transgenic cotton ( Gossypium hirsutum L.) plants. Plant Biotechnology
Journal 2005, 3 in press doi: 10.1111/j.1467-7652.2005.00145
9. Environmental Releases Database for the U.S. 2005 http
://www.nbiap.vt.edu/cfdocs/fieldtests3.cfm
10. Kawata,M, Nakajima,T, Yamamoto,T, Mori,K, Oikawa, T, Fukomoto, F.
and Kuroda, S. Genetic Engineering for Disease Resistance in Rice (
Oryza sativa L.) Using Antimicrobial Peptides JARQ 2003 , 37 (2), 71 –
76 http://www.jircas.af frc.go.jp
11. Open letter from Dr. Takahiro Kanagawa 6 September 2005, forwarded
by Akiko Frid, http ://www.gmwatch.org/archive2.asp?arcid=5689
12. Zhang L, Yu W, He T et al. Contribution of human a- defensin 1, 2,
and 3 to the anti-HIV-! activity of CD8 antiviral factor. Science 2002,
298, 995-1000.
13. Thevissen K, Osborn RW, Acland DP and Broekaert WF. Specific binding
sites for an antifungal plant defensin from Dahlia (Kahlia Merckii) on
fungal cells are required for antifungal activity. Molecular plant-
Microbe Interactions 2000, 13, 55-61.
This article can be found on the ISP website at http://www.indsp.or
g/NRTPAP.php
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