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与牛呼吸道疾病相关的细菌分离株的全基因组测序以及抗菌药物敏感性基因型与表型之间的一致性

Whole-Genome Sequencing and Concordance Between Antimicrobial Susceptibility Genotypes and Phenotypes of Bacterial Isolates Associated with Bovine Respiratory Disease.

作者信息

Owen Joseph R, Noyes Noelle, Young Amy E, Prince Daniel J, Blanchard Patricia C, Lehenbauer Terry W, Aly Sharif S, Davis Jessica H, O'Rourke Sean M, Abdo Zaid, Belk Keith, Miller Michael R, Morley Paul, Van Eenennaam Alison L

机构信息

Department of Animal Science, University of California, Davis, California 95616.

Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523.

出版信息

G3 (Bethesda). 2017 Sep 7;7(9):3059-3071. doi: 10.1534/g3.117.1137.

Abstract

Extended laboratory culture and antimicrobial susceptibility testing timelines hinder rapid species identification and susceptibility profiling of bacterial pathogens associated with bovine respiratory disease, the most prevalent cause of cattle mortality in the United States. Whole-genome sequencing offers a culture-independent alternative to current bacterial identification methods, but requires a library of bacterial reference genomes for comparison. To contribute new bacterial genome assemblies and evaluate genetic diversity and variation in antimicrobial resistance genotypes, whole-genome sequencing was performed on bovine respiratory disease-associated bacterial isolates (, , , and ) from dairy and beef cattle. One hundred genomically distinct assemblies were added to the NCBI database, doubling the available genomic sequences for these four species. Computer-based methods identified 11 predicted antimicrobial resistance genes in three species, with none being detected in While computer-based analysis can identify antibiotic resistance genes within whole-genome sequences (genotype), it may not predict the actual antimicrobial resistance observed in a living organism (phenotype). Antimicrobial susceptibility testing on 64 , , and isolates had an overall concordance rate between genotype and phenotypic resistance to the associated class of antimicrobials of 72.7% ( < 0.001), showing substantial discordance. Concordance rates varied greatly among different antimicrobial, antibiotic resistance gene, and bacterial species combinations. This suggests that antimicrobial susceptibility phenotypes are needed to complement genomically predicted antibiotic resistance gene genotypes to better understand how the presence of antibiotic resistance genes within a given bacterial species could potentially impact optimal bovine respiratory disease treatment and morbidity/mortality outcomes.

摘要

延长的实验室培养和抗菌药物敏感性测试时间线阻碍了与牛呼吸道疾病相关的细菌病原体的快速物种鉴定和敏感性分析,而牛呼吸道疾病是美国牛死亡的最主要原因。全基因组测序为当前的细菌鉴定方法提供了一种无需培养的替代方法,但需要一个细菌参考基因组库进行比较。为了贡献新的细菌基因组组装,并评估抗菌药物耐药基因型的遗传多样性和变异,对来自奶牛和肉牛的与牛呼吸道疾病相关的细菌分离株(、、和)进行了全基因组测序。100个基因组不同的组装被添加到NCBI数据库中,使这四个物种的可用基因组序列增加了一倍。基于计算机的方法在三个物种中鉴定出11个预测的抗菌药物耐药基因,在中未检测到任何耐药基因。虽然基于计算机的分析可以在全基因组序列(基因型)中鉴定抗生素耐药基因,但它可能无法预测在活生物体中观察到的实际抗菌药物耐药性(表型)。对64个、和分离株进行的抗菌药物敏感性测试显示,基因型和表型对相关抗菌药物类别的耐药性之间的总体一致性率为72.7%(<0.001),表明存在显著差异。不同抗菌药物、抗生素耐药基因和细菌物种组合之间的一致性率差异很大。这表明需要抗菌药物敏感性表型来补充基因组预测的抗生素耐药基因基因型,以便更好地了解给定细菌物种中抗生素耐药基因的存在如何可能影响最佳的牛呼吸道疾病治疗以及发病率/死亡率结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/5592931/ea7971d4f860/3059f1.jpg

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