Animal Feed and Antibiotic Resistance

Abstract & Commentary

Synopsis: An antibiotic preparation meant for addition to animal feed was found to be contaminated with antibiotic resistance genes.

Source: Lu K, et al. Antimicrobial resistance gene delivery in animal feeds. Emerg Infect Dis. 2004;10:679-683.

Lu and colleagues at the university of british Columbia and the University of California (Berkeley) detected large amounts of DNA (31 mg/g of antibiotic) in a preparation of the glycopeptide antibiotic avoparcin that was meant for use in animal feed as a growth promoter. Sequencing of the amplicon produced using primers specific for streptomycete 16S rRNA found it to be closely related to that of Amycolatopsis coloradensis, the producer source of avoparcin. Further analysis detected the presence of a cluster of genes encoding proteins with > 50% amino acid identity with the Van H, A, and X proteins of vancomycin-resistant enterococci (VRE).

Comment by Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center and Editor of Infectious Disease Alert.

VRE were first detected in Europe, primarily as colonizing organisms in healthy individuals in the community.1 This contrasted with the subsequent emergence of VRE in the United States, where gastrointestinal colonization in healthy individuals was uncommon as it became increasingly prevalent among hospitalized patients. This difference was believed to be the result of different locations in which the selective pressure of glycopeptide use was exerted in the 2 continents. Thus, vancomycin use in US hospitals far exceeded the rather meager use in European hospitals. On the other hand, the use of the vancomycin-related glycopeptide antibiotic, avoparcin, was widespread as an agricultural growth promoter in animal feed in Europe, but similar antibiotics were not used for this purpose in the United States. This is believed to have led to the emergence of VRE in farm animals, in whom the organisms were readily detected, both on the farm, and on, for example, chicken for sale in supermarkets. Such food thus served as the community reservoir that led to gastrointestinal colonization of healthy humans.

Vancomycin resistance in Enterococcus, however, requires the presence of a large gene cassette encoding a series of proteins that affect synthesis and modification of cell wall components. In the absence of these genes, the pressure exerted by avoparcin could not have resulted in the emergence of VRE. Where did these genes come from?

Lu et al provide a possible answer. Organisms that produce antibiotics must have a mechanism to protect themselves from their antimicrobial effect, as is the case with the source of vancomycin, A coloradensis. This study shows that feed-grade avoparcin is contaminated with bacterial DNA, including DNA encoding vancomycin resistance genes. These genes could have the potential for incorporation into enterococci in the gastrointestinal tract of the animals ingesting this contaminated feed. Ingesting the antibiotic would then select out any resistant enterococci that resulted from this sequence of events.

Avoparcin was added to animal feed in Europe from 1975 through 1996, when its use was discontinued by fiat of the European Union. Since then, there has been a significant decrease in VRE contamination of meat products, particularly poultry.2 Its use continues to be banned in the United States. Other antibiotics are, however, used as agricultural growth promoters in this country, and it seems likely that a similar circumstance may apply.

One more thing: Antibiotic resistance genes are commonly being engineered into transgenic plants, including some used as animal feed.3 Investigations and expert opinions suggest that transfer into gastrointestinal bacteria, while theoretically possible, is highly unlikely.4 Fortunately, the genes being used generally encode for resistance mechanisms that are already highly prevalent in gastrointestinal bacteria.

References

1. Bonten MJ, et al. Vancomycin-resistant enterococci: Why are they here, and where do they come from? Lancet Infect Dis. 2001;1:314-325.

2. Del Grosso M, et al. Detection and characterization of vancomycin-resistant enterococci in farm animals and raw meat products in Italy. Microb Drug Resist. 2000; 6:313-318.

3. Chambers PA, et al. The fate of antibiotic resistance marker genes in transgenic plant feed material fed to chickens. J Antimicrob Chemother. 2002;49:161-164.

4. Bennett PM, et al. An assessment of the risks associated with the use of antibiotic resistance genes in genetically modified plants: Report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother. 2004;53:418-431.