Use of Antibiotics in Agriculture
Virginia Stockwell, Department of Botany and Plant Pathology, Oregon State University,
Corvallis, Oregon, 97330, USA email: stockwev@science.oregonstate.edu
Bacterial diseases of plants are difficult to manage, in part because there are few effective
materials for control. Since the 1950s, antibiotics have been important tools for the
management of several bacterial diseases, such as fire blight of pear and apple, bacterial
spot of peach, bacterial panicle blight of rice and assorted bacterial diseases of vegetable
crops. Common attributes of these aerial diseases are that the pathogen has a critical
growth phase on exposed plant surfaces prior to infection and the infection period is limited.
To control plant diseases, antibiotics are applied as prophylactic sprays on plant surfaces to
inhibit pathogen growth before infection; antibiotic sprays do not cure plants of disease
after infection.
While antibiotics can reduce the incidence of bacterial diseases of plants, long term efficacy
and use of antibiotics on plants is threatened by the development of resistance in the
targeted plant pathogens and by challenges to registration of these compounds by
governmental agencies in response to concerns that antibiotic applications on plants may be
harmful to the environment or human health.
Only five antibiotics are used for plant disease control around the world. Oxytetracycline is
permitted on crops in the USA, Mexico, and Central America. Oxolinic acid (a quinolone
antibiotic) is used in Japan and Israel on rice and pome fruits, respectively. Three
aminoglycosides, streptomycin, gentamicin, and kasugamycin, are used on plants.
Gentamicin is used in Mexico and Central America and kasugamycin is registered in Canada.
Of the antibiotics, streptomycin is used in the greatest number of countries. Streptomycin is
registered for control of fire blight of pear and apple, caused by Erwinia amylovora, in North
America, New Zealand, Israel and may be permitted on a tightly regulated emergency-use
basis, in Austria, Germany and Switzerland (Stockwell and Duffy 2012).
Records of worldwide use of antibiotics in plant agriculture are incomplete. Usage data on
antibiotics in plant agriculture in the USA can be found in publicly available databases on the
United States Department of Agriculture National Agricultural Statistics Service website
(www.nass.usda.gov). Efforts to obtain antibiotic use data on crops in other countries have
been unsuccessful.
In the USA, ~10% of the total peach acreage is treated annually with two to three
applications of oxytetracycline to control bacterial spot. About 90% of the quantity of
streptomycin and oxytetracycline used in plant agriculture is applied to pear and apple trees
to control fire blight caused by Erwinia amylovora. Antibiotics are sprayed on trees in bloom
when warm springtime temperatures (>15°C) support rapid growth of the pathogen on
newly opened flowers. Across the USA, weather conditions often are too cool during bloom
for high disease risk, and consequently the majority of orchards are not treated and the
number of applications is limited. In the USA, only 20% of the apple acreage is treated with
antibiotics one or two times during bloom. The heaviest use of antibiotics is on pear, a plant
particularly sensitive to fire blight. Approximately, 40% of the pear acreage in the USA is
treated with three to four applications of antibiotics. In 2009, a total of 16,465 kg of
antibiotics were applied to orchards in the USA. While this may seem like a large quantity of
antibiotics, consider that it is only 0.12% of the total amount of antibiotics used in animal
agriculture in the USA.
Of the antibiotics used on plants, oxolinic acid and the aminoglycosides gentamicin and
streptomycin are classified as ‘Critically Important Antimicrobials’ to human health by the
World Health Organization (http://www.who.int/foodborne_disease/resistance/cia/en/).
Oxytetracycline is categorized as a ‘Highly Important Antimicrobial’ by the same agency.
Consequently, the wisdom of using these antibiotics for crop protection has come under
scrutiny. The following presents a brief summary of results of recent research that addresses
some of the common questions about the impact of antibiotics on the environment and
possible effects on human health.
1) Do antibiotic applications introduce resistance genes in the environment? Plant-grade
formulations of streptomycin from several countries were tested for bacterial DNA and
mobile streptomycin-resistance genes (Rezzonico et al., 2009). None of the formulations
contained detectable quantities of DNA or streptomycin-resistance genes. Thus, it is unlikely
that the plant-grade antibiotics are a source of resistance genes in the environment.
2)
Do antibiotic sprays increase prevalence of antibiotic-resistant clinical bacteria in
orchards? There is no evidence that antibiotic sprays increase the prevalence of antibioticresistant clinical bacteria on plants. Clinical bacteria were not identified in recent
metagenomic studies of bacterial communities from apple leaves (Yashiro and McManus,
2012) and apple flowers (Shade et al., 2013). Plant-associated bacterial communities from
leaves in apple orchards with a 10-year history of streptomycin applications were similar to
those from non-sprayed orchards and the incidence of streptomycin-resistant bacteria
(~50%) was similar in sprayed and non-sprayed orchards (Yashiro and McManus, 2012).
Application of streptomycin on apple flowers also resulted in minimal community-level
responses (Shade et al., 2013). In another study on antibiotic-treated coriander, the
abundance of antibiotic-resistant bacteria, resistance genes, or plasmids from plants or soil
was not changed by repeated applications of gentamicin and oxytetracycline (RodriguezSanchez, et al., 2008). Similar results were observed in soils in orchards treated with
streptomycin (Duffy et al, 2014). Overall, the influence of antibiotic applications on the
community structure of plant-associated bacteria and their antibiotic resistance profile is
considered minor and short-lived (McManus, 2014).
3)
Are residues of antibiotics active and present in high concentrations in the
environment and on crops? The duration of antibiosis is short-lived on plant tissues.
Antibiotics inhibit the growth of antibiotic-sensitive bacteria on flower and leaf surfaces for
less than five days after application (Stockwell et al., 2008; Vanneste, 1996). Exposure to
sunlight can degrade antibiotics and rainfall can reduce concentrations on plant surfaces
rapidly (Christiano et al., 2010). Soil particles absorb and inactivate some antibiotics, such as
tetracyclines (Subbiah et al., 2011).
Direct exposure of consumers to antibiotic residues on crops is minimized because
antibiotics may not applied to plants within a month before harvest. Permissible antibiotic
residue concentrations on pome fruit are 0.25 to 0.35 mg/kg (McManus et al., 2002). In a
recent study, the highest concentration of streptomycin quantified on apple fruit from
orchards sprayed three times was 0.018 mg/kg (Mayerhofer et al., 2009). In that study,
most apples did not have quantifiable residues of streptomycin. To put the maximum
detected residue level detected in perspective, we need to consider the acceptable daily
intake (ADI) for streptomycin. The ADI is the quantity of a compound that humans can
ingest each day over their lifetime that is expected to have no appreciable effect on health.
In Austria, the ADI for streptomycin is 0.03 mg/kg of body mass, or in other words, a 100 kg
person could safely consume 3 mg streptomycin each day. Assuming that all apple fruits
contained the maximum streptomycin residue detected (0.018 mg/kg fruit), a 100 kg person
could eat 167 kg of fruit or >1,100 apples (150 g average weight) every day before reaching
the 3 mg ADI for streptomycin.
Although many have speculated that spraying plants with antibiotics must have detrimental
effects on the environment and ultimately human health, the current data using
sophisticated molecular and chemical technologies have not supported those concerns.
Nevertheless, the development of antibiotic resistance in targeted plant pathogenic bacteria
is a real concern for the long-term and sustainable use of antibiotics for plant disease
control. For example, after streptomycin was registered for plant disease control, apple and
pear growers applied the antibiotic in orchards on a calendar basis, with up to 20
applications per year. Within 10 years, disease-control failures were reported and isolates of
E. amylovora with resistance to streptomycin were discovered (Jones and Schnabel 2000,
McManus et al, 2002). Plant disease risk models (Billing 2000), based on environmental
parameters and the potential of pathogen populations present in orchards, were developed
and their adoption has reduced the numbers of antibiotic applications.
Even so, reducing the number of antibiotic treatments greatly can still lead to selection of
antibiotic-resistant plant pathogens. Thus, it is important that growers monitor pathogen
populations for resistance to antibiotics to avoid unwarranted and ineffective use of
antibiotics for crop protection. In addition to conducting routine surveillance programs for
resistance, many growers apply combinations of antibiotics or alternate antibiotics to reduce
the selection pressure for antibiotic-resistant isolates of the target pathogen. Some growers
also employ biological control agents in their disease-management programs. For example,
improved control of fire blight has been obtained by establishing suppressive populations of
the biocontrol agent Pseudomonas fluorescens strain A506 on flowers during early bloom,
followed by a single application of an antibiotic if disease risk is high (Lindow et al., 1996,
Stockwell et al., 2008). This ‘probiotic-like’ approach may further reduce the numbers of
antibiotic applications to crops and slow the emergence of antibiotic-resistant pathogens.
Overall, antibiotics have been indispensable for crop protection for more than 60 years
without reports of adverse effects on human health or the environment. The prudent use of
antibiotics in cropping systems will contribute to the long-term efficacy of these important
tools for the management of bacterial diseases of plants.
Selected references
Billing, E. 2000. Fire blight risk assessment systems and models. In Fire blight: the disease
and its causative agent, Erwinia amylovora (J. Vanneste, ed.). CAB International,
Wallingford, UK, 293–318.
Christiano R.S.C., Reilly C.C., Miller W.P. & Scherm H. 2010. Oxytetracycline dynamics on
peach leaves in relation to temperature, sunlight, and simulated rain. Plant Dis., 94,
1213–1218.
Duffy, B., Holliger, E., and Walsh, F. 2014. Streptomycin use in apple orchards did not
increase abundance of mobile resistance genes. FEMS Microbiol. Lett. 350:180-189
Johnson K.B. & Stockwell V.O. 1998. Management of fire blight: a case study in microbial
ecology. Annu. Rev. Phytopathol., 36, 227–248.
Jones, A.L., and Schnabel, E.L. 2000. The development of streptomycin-resistant strains of
Erwinia amylovora. In Fire blight: the disease and its causative agent, Erwinia amylovora
(J. Vanneste, ed.). CAB International, Wallingford, UK, 235-252.
Lindow S.E., McGourty G. & Elkins R. 1996. Interactions of antibiotics with Pseudomonas
fluorescens A506 in the control of fire blight and frost injury of pear. Phytopathology, 86,
841–848.
Mayerhofer, G., Schwaiger-Nemirova, I., Kuhn, T., Girsch, L., and Allerberger, F. 2009.
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Chemother. 63:1076 -1077.
McManus P.S. 2014. Does a drop in the bucket make a splash? Assessing the impact of
antibiotic use on plants. Curr. Opin. Microbiol. 19:76-82.
McManus P.S., Stockwell V.O., Sundin G.W. & Jones A.L. 2002. Antibiotic use in plant
agriculture. Annu. Rev. Phytopathol., 40, 443–465.
Rezzonico F., Stockwell V.O. & Duffy B. 2009. Plant agriculture streptomycin formulations do
not carry antibiotic resistance genes. Antimicrob. Agents Chemother. 53, 3173–3177.
Rodriguez-Sanchez C., Altendorf K., Smalla K. & Lipski A. 2008. Spraying of oxytetracycline
and gentamicin onto field-grown coriander did not affect the abundance of resistant
bacteria, resistance genes, and broad host range plasmids detected in tropical soil
bacteria. Biol. Fertil. Soils, 44, 589–596.
Shade, A., McManus, P.S., and Handelsman, J. 2013. Unexpected diversity during community
succession in the apple flower microbiome. mBio 4: doi:10.1128/mBio.00602-12.
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Stockwell V.O., Temple T.N., Johnson K.B. & Loper J.E. 2008. Integrated control of fire blight
with antagonists and oxytetracycline. Acta Horticult. 793, 383–390.
Subbiah M., Mitchell S.M., Ullman J.L. & Call D.R. 2011. β-lactams and florfenicol antibiotics
remain bioactive in soils while ciprofloxacin, neomycin, and tetracycline are neutralized.
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Yashiro E. & McManus P.S. 2012. Effect of streptomycin treatment on bacterial community
structure in the apple phyllosphere. PLoS ONE, 7, e37131.