Polymer dendrimers as potent and selective inhibitors of bacterial crop diseases

Unmet Need

Currently, the agriculture industry relies on broad-spectrum antibiotics to ensure high crop yields, but farmers still suffer losses of 17-30% to disease and blight. Furthermore, the use of broad-spectrum antibiotics to treat these diseases leads to environmental antibiotic resistance, which can in turn create antibiotic-resistant human diseases and decimate beneficial microbes that maintain nutrient levels in soil. Bacterial pests are particularly devastating in fruit orchards, where trees are planted close together, allowing diseases to spread easily. One such disease, fire blight, causes great annual losses for apple growers and restricts the geographic locations of sustainable pear production. Additionally, kiwi bacterial canker, is a serious, emerging, pandemic disease which almost destroyed kiwi industry in New Zealand. Thus, more selective antimicrobial treatments are needed to prevent crop deaths from bacterial plant diseases.

Technology

Duke inventors have developed a class of selective antimicrobials that target and eliminate bacterial plant diseases including fire blight and kiwi bacterial diseases. These are intended to be used by growers to treat orchards and large-scale farms to prevent the spread of fire blight and kiwi bacterial diseases and increase crop yields. Specifically, the polyamidoamine (PAMAM) dendrimer is a small molecule that targets the largest family of pore-forming virulence proteins that are found in a variety of bacterial plant pathogens belonging to Erwinia spp., Dickeya spp., Pantoea spp. Pectobacterium spp., and all Pseudomonas syringae pathovars, which collectively cause disease in virtually all crop plant species. The molecule’s branched shape is wide enough to simply block the pore hole, thereby preventing the pathogenic action of this key family of virulence proteins. This has been demonstrated to be effective in stopping Erwinia amylovoa, which causes fire blight, as well as a Pseudomonas syringae strain that simulates kiwi bacterial canker-causing agent. Unlike nonspecific antibiotics, current data shows that these molecules are not active against plants or the microbiome, limiting the ability for resistance to spread and ensuring its specificity to plant pathogens.

Other Applications

Because pore-forming virulence factors are produced by many bacterial, fungal and oomycete pathogens, this technology, based on the concept of inhibition of microbial pores, has potential to be used to treat many other plant (and animal/human) pathogens in addition to fire blight and kiwi bacterial canker disease. Further research is needed.

Advantages

• Works during active infection only, preventing resistance and overuse
• More selective than broad spectrum antibiotics, prevents environmental antibiotic resistance
• Does not kill beneficial soil bacteria as broad-spectrum antibiotics do