Phage Biotechnology to Mitigate Antimicrobial Resistance in Agriculture

Abstract

The prevalence of key antibiotic resistant bacteria was reported by the World Health Organization in 2014 and they found very high rates of resistance in all regions of the globe. The United States Centres for Disease Control has also estimated that 20% of the two million antibiotic resistant infections in the US are linked to agricultural use. Antibiotics provide a vital function in reducing mortality in humans and animals, so their efficacy must be protected by coordinated action across multiple sectors, including agriculture. Alongside better antibiotic stewardship, a key to achieving this goal must be the development of new antimicrobial agents. For agriculture, a renewed focus on intensification, food security and reduced food loss also provide additional pressures on controlling bacterial infections and spoilage. Here, we discuss the potential of a new class of antimicrobial agents, phages, as a replacement or supplement, to some of the conventional antibiotics currently used in agriculture. We show that phages have many of the desirable properties needed to control bacterial diseases in agriculture including efficacy, low levels of resistance, lack of cross-resistance to antibiotics, biodegradability and narrow target range.

In poultry, studies of Campylobacter and Salmonella biocontrol have demonstrated that optimal timing for phage application is likely 24–48 h prior to slaughter, up to 5 log reductions in caecal counts may be achieved, and that phage resistance is low and transient. Use of phages in market swine has shown that they are able to reduce Salmonella carriage in tonsils and caeca by up to 3 logs and reduce overall carriage by 50%. Reductions in the shedding of Clostridium and E. coli in piglets have also been observed following phage application. Phages have shown efficacy in reducing Staphylococcus aureus infections in mouse models of mastitis and have reduced disease progression by up to 81% in cows’ udders. Calves were protected from diarrhoea onset and death due to E. coli and Salmonella infection where phages were administered. Complete suppression of wilting was observed when phages were applied to tomato and a 50% reduction when applied in rice wilt. For soft rot disease associated with potatoes, a 94% reduction in rotten tissue was seen in plants treated with phages. Up to 90% reductions in Erwinia were achieved with phage treatment of flowers for fireblight. Additionally, the use of phages may provide new opportunities to agricultural industries to control pathogens not currently effectively controlled by antibiotics or other treatments. However, it is evident that application of phages to each system needs to be tailored and optimised, and that some systems are more challenging for phage use than others (e.g. poultry appear more suited than beef cattle). Whilst there are few phage products available currently, it is likely we will see a rapid rise in their use in the coming years.