Investigating Effects of Tulathromycin Metaphylaxis on the Fecal Resistome and Microbiome of Commercial Feedlot Cattle Early in the Feeding Period

Abstract

The objective was to examine effects of treating commercial beef feedlot cattle with therapeutic doses of tulathromycin, a macrolide antimicrobial drug, on changes in the fecal resistome and microbiome using shotgun metagenomic sequencing. Two pens of cattle were used, with all cattle in one pen receiving metaphylaxis treatment (800 mg subcutaneous tulathromycin) at arrival to the feedlot, and all cattle in the other pen remaining unexposed to parenteral antibiotics throughout the study period. Fecal samples were collected from 15 selected cattle in each group just prior to treatment (Day 1), and again 11 days later (Day 11). Shotgun sequencing was performed on isolated metagenomic DNA, and reads were aligned to a resistance and a taxonomic database to identify alignments to antimicrobial resistance (AMR) gene accessions and microbiome content. Overall, we identified AMR genes accessions encompassing 9 classes of AMR drugs and encoding 24 unique AMR mechanisms. Statistical analysis was used to identify differences in the resistome and microbiome between the untreated and treated groups at both timepoints, as well as over time. Based on composition and ordination analyses, the resistome and microbiome were not significantly different between the two groups on Day 1 or on Day 11. However, both the resistome and microbiome changed significantly between these two sampling dates. These results indicate that the transition into the feedlot—and associated changes in diet, geography, conspecific exposure, and environment—may exert a greater influence over the fecal resistome and microbiome of feedlot cattle than common metaphylactic antimicrobial drug treatment.

Antimicrobial Resistance in Veterinary Medicine: An Overview

“…Analogous effects are amenable to the use of antibiotics for prophylactic purposes [76,77]. In this view, antimicrobial compounds were commonly administered with the drinking water or the feed ration, ensuring a prolonged exposition of the animals to the low dosage of antibiotics for a prolonged time.…”

“…Prophylactic-oriented administration of antibiotics in cattle husbandries expect the oral administration mainly to prevent respiratory diseases and/or liver abscesses [77,78]. Moreover, wide-spectrum antibiotics are administered intramammary during the non-lactating period, to prevent/reduce the incidence of mastitis in lactating animals [72].…”

Antimicrobial Resistance in Members of the Bacterial Bovine Respiratory Disease Complex Isolated from Lung Tissue of Cattle Mortalities Managed with or without the Use of Antimicrobials

“…Gautier-Bouchardon et al [60] analyzed MICs for MB from cattle in France over 30 years, finding substantial increases for some macrolides (tylosin, tilmicosin, tulathromycin) and not others (gamithromycin, tildipirosin. In North America, CON calves would usually get a metaphylactic injection of tulathromycin on arrival at the feedlot [61] and tulathromyin is also used to treat active cases of BRD. Exposure to tulathromycin has increased its MIC in MH and not PM [62], in agreement with the results of our study for MH, although increased MICs for tulathromycin could also be influenced by co-selection.…”

Host genetics affected the resistome and its expression patterns in the rumen of beef cattle raised without antibiotics used in humans

“…In addition, the diversity and abundance of total ARGs were higher in the rumen of beef cattle fed high concentrate than those fed high forage diet, with chloramphenicol and aminoglycoside resistance genes being predominant in forage-and concentrate-fed cattle, respectively [13]. A recent study also suggested that the dietary supplementation of tulathromycin, a macrolide antimicrobial drug used as metaphylaxis, signi cantly affected the temporal development of fecal microbiota and associated resistome in feedlot cattle [51]. To our knowledge, there is no study reporting how host genetic factors affect the active gut resistome in mammalian species.…”