Antibiotic Use in Plant Disease Control

Patricia S. McManus
Department of Plant Pathology
University of Wisconsin-Madison
psm@plantpath.wisc.edu

A wide range of food crops and ornamental plants are susceptible to diseases caused by bacteria. Bacterial diseases of plants are notoriously difficult to control and often result in sudden, devastating financial losses to farmers. In the 1950s, soon after the introduction of antibiotics into the field of human medicine, the potential for these "miracle drugs" to control plant diseases was recognized. Unfortunately, just as the emergence of antibiotic resistance sullied the miracle in clinical settings, resistance has also limited the value of antibiotics in crop protection.

In recent years, antibiotic use on plants, and in particular the potential impact of this practice on human health, has been fiercely debated in several countries. This article will focus primarily on the situation in the United States, where I have been best able to access antibiotic use data and research reports. The objectives of this article are to i) present the practical and political aspects of antibiotic use on plants; ii) present special aspects of plant use that may impact the development and persistence of antibiotic resistance genes in agroecosystems; and iii) challenge agencies that have traditionally been parochial in their funding to view antibiotic resistance as a universal phenomenon in need of multidisciplinary research and education.

Practical and political aspects. The diversity and quantity of antibiotics used for plant disease control is meager compared to medical and veterinary uses. In the United States, streptomycin is registered for use on twelve fruit, vegetable, and ornamental plant species; oxytetracycline is registered for use on four fruit crops (Table 1). Both antibiotics are applied primarily for the control of bacterial diseases, although streptomycin is also used to a limited extent to control diseases caused by water molds, and oxytetracyline has been used to control certain diseases caused by phytoplasmas (mycoplasma-like organisms that infect plants). Tree fruits account for the majority of antibiotic use on plants in the U.S. In 1995, approximately 25,000 lbs and 13,700 lbs (active ingredient) of streptomycin and oxytetracycline, respectively, were applied to fruit trees in the major tree-fruit states (12). Antibiotics were applied to less than 20% of apple, 35-40% of pear, and 4% of peach acreage. At less than 0.1% of total antibiotic use in the U.S., plant use truly represents a "drop in the bucket".

Streptomycin resistance in plant pathogens and the molecular nature of resistance is summarized in Table 2 and in greater detail by Sundin and Bender (19, 20). Surveys have not revealed oxytetracycline resistance in plant pathogenic bacteria but have identified tetracycline-resistance determinants in nonpathogenic orchard bacteria (13). Two genetically distinct types of streptomycin resistance have been described (2-4): i) a point mutation in the chromosomal gene rpsL which prevents streptomycin from binding to its ribosomal target (MIC >1,000 m g/ml); or ii) inactivation of streptomycin by phosphotransferase, an enzyme encoded by strA and strB (MIC 500-750 m g/ml). The genes strA and strB usually reside on mobile genetic elements and have been identified in at least 17 environmental and clinical bacteria populating diverse niches (19).

Because antibiotics are among the most expensive of pesticides used by fruit and vegetable growers, and their biological efficacy is limited, many growers use weather-based disease prediction systems to ensure that antibiotics are applied only when they are likely to be most effective. Growers can also limit antibiotic use by planting disease resistant varieties and, in some cases, using biological control (applying saprophytic bacteria that are antagonistic to pathogenic bacteria). Despite these efforts to reduce growers’ dependency on antibiotics, these chemicals remain an integral part of disease management, especially for apple, pear, nectarine, and peach production.

Antibiotic use on crops and ornamental plants in the U.S. is regulated by the Environmental Protection Agency. Product labels and supplemental literature clearly state what type of clothing, boots, gloves, and respirators must be worn by mixers, applicators, and persons entering a treated area after antibiotics have been applied. These documents are legally binding, and it is a violation of federal law to use an antibiotic in a manner inconsistent with its labeling. In addition to federal laws, states have pesticide laws and help enforce the federal mandates. Thus, although the application of antibiotics to plants is markedly different from clinical use and may appear to occur under uncontrolled conditions (i.e., the open environment), it is a highly regulated activity; farmers are bound by stringent measures to protect the health of workers and the environment.

Given these seemingly rigid regulations, does antibiotic use on plants pose risks to human health? One consumer advocacy group has argued that applying antibiotics to crops is an imprudent luxury that may eventually lead to the demise of life-saving drugs (7). Growers, however, defend their practice as being so limited in scope as to be inconsequential to human and environmental health. Unfortunately, both sides lack of sound, quantitative data to uphold their positions. For now, this leaves us with a contentious debate based on circumstantial evidence and fueled by passion. On the one hand, fruit and vegetable producers have sizable economic interests (including their very livelihoods) at stake when dealing with bacterial diseases. The amount of antibiotics used in plant disease control is minuscule compared to total use, and no apparent human health issues have arisen after four decades of use. On the other hand, medical experts have witnessed the failure of one antibiotic after another in clinical settings which, at least superficially, appear to be much more confined and strictly controlled than farm settings.

Special aspects of antibiotic use on plants. Although antibiotic use on plants is minor relative to total use, application of antibiotics in the agroecosystem presents unique circumstances that could impact the build up and persistence of resistance genes in the environment. The following scenarios are presented to provoke interest and possibly spark research enterprises, not to condemn current agricultural practices or provide ammunition for those seeking to ban the use of antibiotics for plant disease control.

First, antibiotics are applied over physically large expanses. In regions of dense apple, pear, nectarine, or peach production, antibiotics are applied to hundreds of hectares of nearly contiguous orchards. Moreover, the past decade has seen a dramatic increase in the planting of apple varieties and rootstocks that are susceptible to the devastating bacterial disease, fire blight. This has created a situation analogous to clinical settings where immune-compromised patients are housed in crowded conditions—settings associated with the proliferation and spread of antibiotic-resistance genes.

Second, the purity of antibiotics used in crop protection is unknown. Reagent and veterinary grade antibiotics have been found to contain antibiotic resistance genes from the producing Streptomyces spp. (22). Plant-grade antibiotics are unlikely to be purer than those used for treating animals and may themselves be an origin of antibiotic-resistance genes in agroecosystems. The genes that were amplified from antibiotics, otrA and aphE, are different from the resistance genes strA and strB that have been described in plant-associated bacteria (2, 17). Thus, it may be that plant-grade antibiotics are a potential origin of resistance genes in the environment but are not necessarily present and active in plant pathogenic bacteria.

Third, fertilizers and fungicides applied throughout the growing season are rich sources of divalent cations. The concentration of Mn²⁺ or Ca²⁺ in these products is on the order of 10-50 mM, the concentration used for chemical transformation of bacteria in the laboratory. Also, the commercial formulation of oxytetracycline (Mycoshield) is a calcium complex. Although natural transformation has been documented for only a few bacterial species, the concurrent application of antibiotics (with resistance genes) and unnaturally high concentrations of divalent cations might promote chemical transformation in planta. DNA is tightly bound by aminoglycoside antibiotics, such as streptomycin, which could protect the DNA from nucleases and even enhance its uptake into bacterial cells (22). Once introduced into the bacteria, the resistance genes would have to be integrated into the bacterial genome by illegitimate recombination, an inefficient process. However, if bacteria acquired resistance genes, even at very low frequencies, exposure to antibiotics would provide the selection pressure needed to convert the initially rare strains into a predominant component of the population.

The challenge for granting agencies. The evolution of antibiotic resistant bacteria is outpacing the discovery of new antibiotics. Fruit and vegetable growers struggle to maintain the registration and efficacy of the only two antibiotics at their disposal. This political battle comes on the heels of the Food Quality Protection Act of 1996, a pesticide law that threatens the registration of several pesticides that fruit and vegetable growers depend on to stay in business. Thus, the stakes are high for both human medicine and food production. Knowledge of the origins and acquisition of antibiotic resistance genes in the environment is central to developing strategies to retain the efficacy of antibiotics to control diseases of humans, animals, and plants. But how will this knowledge develop? There is certainly no shortage of intellect or scientific expertise in the field of antibiotic resistance. Rather, the gap appears to be in joining experts from different disciplines and then persuading granting agencies that have traditionally funded either medical or agricultural research to recognize antibiotic resistance for the global and multidisciplinary phenomenon it is.

*Speciman labels and material safety data sheets available at http://www.greenbook.net/

*References: 1, 2, 5, 6, 8-11, 14-16, 18-21

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