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GMW: Defensins in GMOs indefensible - Independent Science Panel

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GMW: Defensins in GMOs indefensible - Independent Science Panel

" GM WATCH " <info

Tue, 20 Sep 2005 12:05:08 +0100

 

 

 

 

GM WATCH daily

http://www.gmwatch.org

---

EXCERPTS: " 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. "

 

" 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. "

 

For the open letter by Dr. Takahiro Kanagawa referred to here, see:

http ://www.gmwatch.org/archive2.asp?arcid=5689

---

This article can be found on the ISP website at http://www.indsp.or

g/NRTPAP.php

 

The Independent Science Panel

Promotion of Science for the Public Good http://www.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

 

Bulet P, Stocklin R. and Menin L. Anti-microbial peptides: from

invertebrates to vertebrates Immunol Rev. 2004 ,198,169-84,

Boman, H. Antibacterial peptides: basic facts and emerging concepts. J

Intern Med. 2003, 254(3), 197-215.

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.

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.

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.

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.

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.

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

Environmental Releases Database for the U.S. 2005 http

://www.nbiap.vt.edu/cfdocs/fieldtests3.cfm

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

Open letter from Dr. Takahiro Kanagawa 6 September 2005, forwarded by

Akiko Frid, http ://www.gmwatch.org/archive2.asp?arcid=5689

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.

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.

 

 

 

 

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