Dose-dependent impact of oxytetracycline on the veal calf microbiome and resistome

Autor: Valeria Agamennone, Daniël Mioch, Richard Bomers, Adri van de Braak, Martien P. M. Caspers, Mieke Havekes, Tim J. van den Broek, Roy Christiaan Montijn, Martin van Baak, Lonneke Bomers, Bart J. F. Keijser, Eric Schoen
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0106 biological sciences
Dose
lcsh:QH426-470
medicine.drug_class
Antibiotic resistance
lcsh:Biotechnology
Antibiotics
Sub-therapeutic concentration
Physiology
Oxytetracycline
Microbial Sensitivity Tests
Biology
Gut flora
01 natural sciences
Resistome
03 medical and health sciences
Feces
Random Allocation
In vivo
lcsh:TP248.13-248.65
RNA
Ribosomal
16S

Genetics
medicine
Animals
Microbiome
Minimum selective concentration
030304 developmental biology
0303 health sciences
Gut microbiome
Veal calves
Dose-Response Relationship
Drug

Antibiotic
Drug Resistance
Microbial

Sequence Analysis
DNA

biology.organism_classification
Anti-Bacterial Agents
Gastrointestinal Microbiome
lcsh:Genetics
Genes
Bacterial

Metagenome
Cattle
Metagenomics
010606 plant biology & botany
Biotechnology
medicine.drug
Research Article
Zdroj: BMC Genomics
BMC Genomics, 1, 20
BMC Genomics, Vol 20, Iss 1, Pp 1-14 (2019)
Popis: Background Antibiotic therapy is commonly used in animal agriculture. Antibiotics excreted by the animals can contaminate farming environments, resulting in long term exposure of animals to sub-inhibitory levels of antibiotics. Little is known on the effect of this exposure on antibiotic resistance. In this study, we aimed to investigate the long term effects of sub-inhibitory levels of antibiotics on the gut microbiota composition and resistome of veal calves in vivo. Forty-two veal calves were randomly assigned to three groups. The first group (OTC-high) received therapeutic oral dosages of 1 g oxytetracycline (OTC), twice per day, during 5 days. The second group (OTC-low) received an oral dose of OTC of 100–200 μg per day during 7 weeks, mimicking animal exposure to environmental contamination. The third group (CTR) did not receive OTC, serving as unexposed control. Antibiotic residue levels were determined over time. The temporal effects on the gut microbiota and antibiotic resistance gene abundance was analysed by metagenomic sequencing. Results In the therapeutic group, OTC levels exceeded MIC values. The low group remained at sub-inhibitory levels. The control group did not reach any significant OTC levels. 16S rRNA gene-based analysis revealed significant changes in the calf gut microbiota. Time-related changes accounted for most of the variation in the sequence data. Therapeutic application of OTC had transient effect, significantly impacting gut microbiota composition between day 0 and day 2. By metagenomic sequence analysis we identified six antibiotic resistance genes representing three gene classes (tetM, floR and mel) that differed in relative abundance between any of the intervention groups and the control. qPCR was used to validate observations made by metagenomic sequencing, revealing a peak of tetM abundance at day 28–35 in the OTC-high group. No increase in resistance genes abundance was seen in the OTC-low group. Conclusions Under the conditions tested, sub-therapeutic administration of OTC did not result in increased tetM resistance levels as observed in the therapeutic group. Electronic supplementary material The online version of this article (10.1186/s12864-018-5419-x) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE