48 Current Pharmaceutical Biotechnology, 2010, 11, 48-57 1389-2010/10 $55.00+.00 © 2010 Bentham Science Publishers Ltd. Phage Therapy for Plant Disease Control B. Balogh 1,2 , Jeffrey B. Jones 1,* , F.B. Iriarte 1,3 and M.T. Momol 1,4 1 University of Florida, 1453 Fifield Hall, Plant Pathology Department, Gainesville, FL 32611, USA; 2 The Connecticut Agricultural Experiment Station, Department of Plant Pathology and Ecology, 123 Huntington Street, New Haven, CT 06504, USA; 3 Iowa State University, Department of Plant Pathology; 4 North Florida Research and Education Center, University of Florida, Quincy, FL 32351, USA Abstract: Bacteria cause a number of economically important plant diseases. Bacterial outbreaks are generally problem- atic to control due to lack of effective bactericides and to resistance development. Bacteriophages have recently been evaluated for controlling a number of phytobacteria and are now commercially available for some diseases. Major chal- lenges of agricultural use of phages arise from the inherent diversity of target bacteria, high probability of resistance de- velopment, and weak phage persistence in the plant environment. Approaches for resistance management - by applying phage mixtures and host-range mutant phages and, for increasing residual activity, by employing protective formulations, avoiding sunlight, and utilizing propagating bacterial strains - resulted in better efficacy and reliability. Deployment of phage therapy as part of an integrated disease management strategy, which includes the use of genetic control, cultural control, biological control, and chemical control, also has been investigated and will likely increase in the future. Keywords: Bacteriophage, biological control, phytobacteria, plant disease control. INTRODUCTION While the majority of plant pathogens are of fungal ori- gin, bacterial plant pathogens are responsible for major eco- nomic losses in agriculture [1]. Management of bacterial diseases is usually challenging [2] due to (1) lack of effective bactericides; (2) high pathogen variability, (3) rapid popula- tion build-up under optimal conditions, (4) high mutation rates resulting in pesticide resistance development, and (5) high mutation rates also resulting in bacteria overcoming plant genetic resistance (i.e. bacteria-resistant plant geno- types). Most effective plant disease management approaches require an integrated strategy utilizing sound cultural prac- tices, plant genetic resistance, induced resistance, and bio- logical or chemical control agents [3,4]. Early History of Phage Therapy of Plants Bacteriophages were first found in association with plant pathogenic bacteria in 1924, when Mallman and Hemstreet [5] demonstrated that the filtrate of decomposed cabbage inhibited growth of the “cabbage-rot organism,” Xantho- monas campestris pv. campestris. In 1926, Moore proposed that phages may be utilized as agents of disease control [6], and soon thereafter phages were successfully used for the prevention of potato tuber rot caused by Erwinia carotovora subsp. atroseptica [7] and as a seed treatment for reducing incidence of Stewart’s wilt of corn, incited by Pantoea stew- artii [8]. Despite promising early results, phage therapy did not prove to be a reliable and effective method for plant dis- ease control and was deemed as unfeasible by several leaders in the field [9-11]. *Address correspondences to this author at the University of Florida, 1453 Fifield Hall, Plant Pathology Department, Gainesville, FL 32611, USA; Tel: +1-352-392-7244; Fax: +1-352-392-6532; E-mail: jbjones@ufl.edu Chemical Control Agents Despite the early successes observed with phage therapy, eventually chemical control with reliance on antibiotics and copper compounds became the standard means for managing bacterial plant diseases [1]. However, a number of factors necessitated the search for alternatives to chemical control. Copper products have been used for more than a century and are still used extensively, despite the fact that copper- resistant bacterial strains are present in a number of patho- systems, hindering control efficacy. That is, copper resis- tance (both plasmid-borne resistance and of chromosomal origin) has been reported in a number of bacterial plant pathogens [12-17]. Additionally, continuous copper use poses environmental hazards due to build-up to toxic levels in soils [18]. Antibiotics, mainly streptomycin, have also been widely used against phytobacteria, but emergence of resistant strains led to loss of control in several pathosys- tems, including bacterial spot of tomato and pepper and fire blight of apple and pear [16,19-21]. Also, there is a call for phasing out antibiotics from non-medical uses. Concerns about the environmental impact of chemical bactericides coupled with the increasing public demand for environmen- tally sound and sustainable agricultural practices as well as eco-friendly food products reduced the desirability of these products. The result was an implementation of environment- friendly alternatives, such as plant activators (following paragraph) and biological control agents (following section). One environment-friendly alternative is the use of sys- temic acquired resistance (SAR) inducers or plant activators. These are protein or synthetic chemical products that induce plant innate defense systems, triggering a broad spectrum of antibacterial resistance. These proved to be effective against a number of diseases including bacterial spot and speck of tomato and pepper [3,21,22], fire blight on apple [23], and