Sunday, November 13, 2005

Copper fungicide use in farms can promote dangerous bacteria – threatening hospital patients.

(This issue was discussed recently on the <>ABC channel television program Landline , the transcript of which is a great introduction to this topic)

Survival of bacteria in adverse circumstances is promoted by special cellular mechanisms to detoxify chemicals. The biology of these remarkable detoxifying mechanisms has some surprising consequences. One of these is that toxic chemicals permitted in organic farming are relevant to dangerous outbreaks of untreatable infections in today’s hospitals.

The genetic trait of bacterial resistance to toxic heavy metal metals (such as copper or mercury) is similar to the trait of bacterial resistance to antibiotic drugs. Both these types of survival ability involve mobile forms of genes that can be widely transmitted between different species of bacteria. They are transmissible because they are carried in the bacteria on <>mobile mini-chromosomes called plasmids that can be naturally injected from one bacterial cell to another in mating events.

Plasmids that bear resistance traits (eg copper-resistance in multiple-drug resistant plasmids) are thus themselves infectious, and can move from one species of bacterium to another. They are really analogous to dangerous viruses, and plasmids in the soil can become hospital plasmids quite easily. <>Plasmids bearing multiple resistance traits are a major reason why many dangerous bacteria such as Staphylococcus aureus are resistant to most modern antibiotics, and why hospitals outbreaks of infections that are untreatable by any antibiotic currently available are such a terrifying modern reality. We now live in the post-antibiotic era.

Overuse of antibiotics is the main cause of this problem, and restricting the use of antibiotics when they are not vital to human welfare is a good place starting point.

But it is important to bear in mind that antibiotics are not the only selective pressure that promotes spread of multiple-drug resistant plasmids in the environment. Copper resistance is in fact a genetic a trait that is carried by many plasmids. (For example Voloudakis AE, Reignier TM, and Cooksey DA. (Appl Environ Microbiol. 2005 Feb;71(2):782-9. ) describe details of a copper resistance genetic trait carried by plasmids in the plant pathogen Xanthomonas axonopodis pv. vesicatoria. )

Resistance by bacteria to the killing ability to copper can arise, for instance, because of their ability to actively pump toxic excess copper out of the cell, and miniature bacterial pumps that eliminate many different compounds from the bacterial cell (copper included) are common in many organisms. These pumps are often of the type of pump called MDR pumps. Thus copper resistance may directly promote resistance of bacteria to other compounds through the pumping ability of a shared MDR pump.

For many years microbiologists have been investigating the origins of multiple-drug resistant plasmids and the genetic traits – such as copper resistance genes – carried on plasmids. (see for example Ana Alonso, Patricia Sanchez and Jose L. Mart nez Environmental selection of antibiotic resistance genes Environmental Microbiology, 2001, 3, 1-9). In fact is quite likely that resistance to toxic metals, such as copper and mercury, is a primary driver of plasmid evolution, as metals have been around the natural environment for billions of years.

The fact that copper is extremely broad spectrum in its toxicity, is highly persistent in the environment, has been around the environment for billions of years, and that mechanisms of copper risistance are widely spread among different organisms underlines the importance of taking the human welfare implications of copper resistance traits of bacteria seriously.

A recent scientific paper

“Copper amendment of agricultural soil selects for bacterial antibiotic resistance in the field” (J. Berg1,2, A. Tom-Petersen1,2 and O. Nybroe1 Letters in Applied Microbiology 2005, 40, 146–151 765X.2004. (1Department of Ecology, Royal Veterinary and Agricultural University, Frederiksberg C, and 2Department of Microbiology, Danish Institute for Food and Veterinary Research, Copenhagen V, Denmark))

provides strong evidence on why we should be concerned about agricultural use of copper based fungicides as definite activities that promote the spread of multiple-drug resistant bacteria. To quote the Berg 2005 papers’ main conclusion

“The results of this field experiment show that introduction of Cu [copper] to agricultural soil selects for Cu resistance, but also indirectly selects for antibiotic resistance in the Cu-resistant bacteria. Hence, the widespread accumulation of Cu in agricultural soils worldwide could have a significant effect on the environmental selection of antibiotic resistance.”

Over use of copper is an issue in Australian farms. The quote another publication:

“In Australia, copper-containing sprays of various formulations … have been used to control fungal diseases in pome and stone fruit orchards, vineyards and vegetable crops for well over 100 years (Merry et al. 1983). Over 7500 t yr-1 of Cu fungicides have been used, representing 13% of the global total (Lepp and Dickinson 1994). In stark comparison, England and Wales were estimated to use only 8 t of Cu fungicide between them in the year 2000 (Nicholson et al. 2003).

(Lukas Van-Zwieten, Graham Merrington and Melissa Van-Zwieten, 2004. SuperSoil 2004: 3rd Australian New Zealand Soils Conference, 5 – 9 December 2004, University of Sydney, Australia. website

Van-Zweiten go on to explain how copper is a persistent poison that accumulates in the soil:

“Horticultural and viticultural operations with a long history of copper fungicide application have resulted in accumulations of copper in surface horizons (Gallagher et al. 2001; Chaignon et al. 2003). Prolonged use in Europe has lead to high levels in the soil (200-500 mg/kg in France, Brun et al. 1998), which has affected a large portion of agricultural land. An Australian study found up to 250mg/kg total copper in a 20-30 yr old vineyard soil, while 8-14 vineyards studied exceeded 60 mg/kg (Pietrzak and McPhail 2004). Similarly, avocado orchard soils in northern NSW were recently observed to have even greater soil Cu residues (280-340 mg/kg) (Merrington et al. 2002).”

<>Organic farmers generally ban antibiotic use, <>but continue to tolerate use of copper based fungicides. In the GMO Pundit's opinion, if they are to continue to have credibility in providing the community with environmentally virtuous practices, they should be consistent, and ban copper fungicides.

There good synthetic antifungal alternatives to copper but the organic movement decline to use them for no good reason.

For example Anthony Trewavas in

Trewavas, A. 2004.
<>A critical assessment of organic farming-and-food assertions with particular respect to the UK and the potential environmental benefits of no-till agriculture. Crop Prot. 23:757–781.

has provided a critical comparison of mancozeb, a synthetic fungicide, with copper sulphate used by the organics movement.To quote him:

Table 1 makes some limited comparisons between mancozeb, a synthetic copper fungicide usually used to treat late blight, and the organic pesticide equivalent, copper sulphate. The full table can be found in Leake (1999a). In environmental qualities, mancozeb is superior in all categories compared to copper sulphate. In terms of human health, copper sulphate is corrosive and toxic and has caused liver disease in European vineyard workers. Although the EC theoretically banned copper sulphate in 2002, no alternative has been found for organic farmers and thus it continues to be used. The consequences of not using copper sulphate properly have been reported as organic farms acting as repositories of late blight, a serious disease of potato (Eltun, 1996; Zwankhuizein et al., 1998) or seriously damaged orchards (Van Embden and Peakall, 1996). Any sensible approach would determine use based on toxicity.

Leake, A., 1999a. House of Lords Select committee on the European communities. Session 1998–1999, 16th report. Organic farming and the European Union. HMSO, London, pp. 81–91.

Labels: <>Environmental management, <>Organic farming, <>Safety and Regulations

Thomas R. DeGregori, Ph.D.
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University of Houston
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