Effects of low concentrations of erythromycin, penicillin, and virginiamycin on bacterial resistance development in vitro

Beilei Ge,Heather C Harbottle,Marla W Keller,Crystal L Rice-Trujillo,Brooke M Whitney,Silvia A Piñeiro,Xin Li,Stuart A Gaines,Qianru Yang,Sonya M Bodeis Jones,Kelly J Domesle,Shenia R Young,Jeffrey M Gilbert

doi:10.1038/s41598-017-09593-4

Beilei Ge, Heather C Harbottle + Show 11 more

Open Access

https://doi.org/10.1038/s41598-017-09593-4

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Abstract

Distillers grains are co-products of the corn ethanol industry widely used in animal feed. We examined the effects of erythromycin, penicillin, and virginiamycin at low concentrations reflective of those detected in distillers grains on bacterial resistance selection. At 0.1 µg/ml erythromycin, macrolide-resistant mutants were induced in one Campylobacter coli and one Enterococcus faecium strain, while these strains plus three additional C. coli, one additional E. faecium, and one C. jejuni also developed resistance when exposed to 0.25 µg/ml erythromycin. At 0.5 µg/ml erythromycin, a total of eight strains (four Campylobacter and four Enterococcus) obtained macrolide-resistant mutants, including two strains from each genus that were not selected at lower erythromycin concentrations. For penicillin, three of five E. faecium strains but none of five Enterococcus faecalis strains consistently developed resistance at all three selection concentrations. Virginiamycin at two M1:S1 ratios did not induce resistance development in four out of five E. faecium strains; however, increased resistance was observed in the fifth one under 0.25 and 0.5 µg/ml virginiamycin selections. Although not yet tested in vivo, these findings suggest a potential risk of stimulating bacterial resistance development in the animal gut when distillers grains containing certain antibiotic residues are used in animal feed.

Highlights

Distillers grains, co-products of the corn ethanol industry, are widely used animal feed ingredients owing to their abundance and nutritional content[1]
Resistance development was stimulated in some strains of both bacterial genera during culture passages at all three erythromycin selection concentrations, with mutant minimal inhibitory concentration (MIC) ranging from 64 to >2048 μg/ml
Much of the literature on antibiotic resistance focuses on tolerance/adaptation to high dosages that typically occur in a clinical setting

Summary

Introduction

Distillers grains, co-products of the corn ethanol industry, are widely used animal feed ingredients owing to their abundance and nutritional content[1]. Over the past 15 years, the expansion of the U.S domestic ethanol industry has led to an exponential growth in distillers grains feed production[2]. In two nationwide surveys conducted by the U.S Food and Drug Administration’s Center for Veterinary Medicine (FDA/CVM), several antibiotics, including virginiamycin, erythromycin, penicillin, and tylosin, have been detected at low concentrations (0.1 to 1.5 ppm) in some of the distillers grains products analyzed[4, 5]. There is concern that through the feeding of distillers grains, food-producing animals are exposed to these antibiotic residues on a continuous basis, which may give rise to antibiotic-resistant bacteria that could be passed down the food chain[3].

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