Combating Antimicrobial Resistance

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ARS research elucidates the factors associated with antimicrobial resistance (AMR) in agricultural settings and develops tools and alternatives to antibiotics that mitigate AMR for the benefit of human, animal, and ecosystem health. Antimicrobials such as antibiotics will remain an essential tool for treating animal and human diseases, though the growing prevalence of resistant bacteria has garnered global concerns over the prudent use of antibiotics in animals. The following FY 2019 accomplishments highlight ARS advances in optimizing the use of and reducing the need for antibiotics in agriculture. Hyperlinked accomplishment titles point to active parent research projects.

Restoring effectiveness of antibiotics. Penicillins are a class of antibiotics used to treat a wide range of bacterial infections; however, their effectiveness has been limited over the years with the development of antibiotic-resistant microbes. Tunicamycin is a powerful antibiotic that can be combined with penicillins to overcome this resistance, but its toxicity in human and animals prevents it from being used for therapeutic applications. ARS scientists in Peoria, Illinois, developed a technology to chemically modify tunicamycin into less harmful derivatives while still retaining the ability to enhance penicillins. These methods use solid catalysts developed by the researchers to selectively alter specific chemical bonds in the tunicamycin that were shown to be associated with toxicity. The catalyst is easily removed from the reaction, resulting in a clean, safer tunicamycin derivative that can be used for numerous agricultural applications. This technology will allow stakeholders to potentially reduce the use of traditional antibiotics to treat livestock, which will delay antibiotic resistance, and reinstitute the use of previously shelved antibiotics that had been rendered ineffective due to antimicrobial resistance.

AMR distribution differs among methicillin-resistant Staphylococcus aureus (MRSA) isolates from healthcare and agricultural sources. Antimicrobial resistance is an expanding public health concern. Since the discovery of livestock associated MRSA (LA-MRSA), public health concerns have increased surrounding the potential of LA-MRSA isolates to serve as a reservoir for antimicrobial resistance genes. ARS researchers in Ames, Iowa, compared swine-associated LA-MRSA ST5 and human clinical MRSA ST5 isolates for antimicrobial susceptibilities and genes associated with antimicrobial resistance. Swine-associated LA-MRSA ST5 isolates showed resistance to fewer antibiotics than clinical MRSA ST5 isolates from humans with no swine contact. Distinct genomic antimicrobial resistance elements were harbored by each subgroup, with little overlap in shared antimicrobial resistance genes between swine-associated LA-MRSA ST5 and clinical MRSA ST5 isolates. These results are important to public health officials and policymakers because the results demonstrate that swine-associated LA-MRSA ST5 and human clinical MRSA ST5 isolates are separate and distinct, suggesting that swine do not play a major role in maintaining a MRSA ST5 reservoir for humans.

Developing tools to combat AMR in a postharvest fungus of apples. Apples are one of the most consumed fruit in the United States and are stored for 6 to 12 months. During storage, the fruit becomes increasingly susceptible to rot caused by the blue mold fungus, which reduces quality, contributes to waste, and produces the mycotoxin patulin. A new postharvest fungicide for apple fruit was released for use in 2015. ARS researchers in Beltsville, Maryland, in collaboration with Cornell University, determined the sensitivity to patulin of a globally diverse Penicillium spp. population that cause blue mold, developed a discriminatory dose to monitor antimicrobial resistance, and tested the patulin formulation against different fungicide-resistant blue mold isolates. A discriminatory dose for difenoconazole is being used by extension professionals to detect fungicide-resistant strains to maintain efficacy of current postharvest chemicals in the mid-Atlantic and Pacific Northwest regions.

Low-cost anaerobic digester reduces antibiotics in farm waste. On-farm management of wastes ranging from animal manures to plant residues is an important issue because accumulated waste can be sources of pollution and may contain human pathogens. ARS scientists in Beltsville, Maryland, in collaboration with scientists at the University of Maryland, tested an anaerobic digestion system that had been developed for small farms to reduce antibiotic compounds in farm waste. This anaerobic digestion system removed 70 percent of the antibiotic monensin, which is widely used in animal husbandry, from waste. Once implemented, anaerobic digestion systems such as this will have the potential to reduce point source pollution runoff from farms into the Chesapeake Bay and other important watersheds. This information will be important to policymakers and scientists developing methods to reduce on-farm waste.

Investigating susceptibility of foodborne pathogens to commercial and household biocides. Biocides are antimicrobial interventions used to reduce bacterial contamination during processing of retail meat. ARS researchers in Athens, GA designed a high throughput panel of 17 common household and commercially-used biocides to determine the susceptibility of  Salmonella to these compounds and to determine if resistance to biocides correlates with resistance to antibiotics. Multidrug resistant Salmonella isolates were resistant to several biocides (cetylpyridinium chloride, hexadecyltrimethylammonium bromide, citric acid, acidified sodium chlorite, chlorhexidine, arsenite, and arsenate). However, no correlation was detected between susceptibility of Salmonella to the biocides and their antibiotic resistance. As the overall aim in the food industry is to reduce antimicrobial use, this assay and the minimum inhibitory concentration data will be important to help monitor the effect of biocides on both biocide and antimicrobial resistance.

Selective breeding improves resistance to bacterial cold water disease and columnaris disease. Antibiotics are used to control these diseases of rainbow trout and few alternative control strategies currently exist. ARS researchers in Leetown, West Virginia, evaluated the genetics of resistance to both diseases in two rainbow trout populations. Resistance was found to be heritable and favorably linked, suggesting that a rainbow trout’s resistance to both diseases is at least partially due to the same genes. Based on these studies, molecular genetic techniques are now being used to identify the actual genes that affect disease resistance. Commercial breeders who select rainbow trout strains for their improved resistance to only one of the diseases can expect to reduce the impacts of both diseases in their fish populations.