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先前暴露于农业头孢菌素头孢噻呋会损害沙门氏菌圣保尔中携带 bla 基因的质粒的接合。

Prior exposure of agriculture cephalosporin ceftiofur impaired conjugation of bla gene-bearing plasmid in Salmonella Saintpaul.

机构信息

Department of Food Science and Technology, National University of Singapore, Singapore.

Department of Food Science and Technology, Korea National University of Transportation, Chungbuk, Republic of Korea.

出版信息

J Appl Microbiol. 2020 Dec;129(6):1552-1565. doi: 10.1111/jam.14749. Epub 2020 Jul 9.

Abstract

AIMS

Although a link between agricultural cephalosporin use and resistance in Salmonella has been demonstrated with the drug ceftiofur, the underlying mechanism of the correlation is unclear. This study investigated the impact of ceftiofur exposure in S. Saintpaul on ceftriaxone resistance, the gene expression and the conjugative transfer of the bla gene.

METHODS AND RESULTS

Prior ceftiofur exposure caused a twofold increase in MIC from 1024 to 2048 µg ml towards ceftriaxone and increased the enzymatic activity of Bla 2·2 folds from 3·46 to 7·67 nmol nitrocefin hydrolysed min . A threefold upregulation in gene expression of the bla gene was also observed. Donors exposed to ceftiofur subsequently demonstrated a 2·5-fold decrease in transfer efficiency.

CONCLUSIONS

Prior exposure of S. Saintpaul to ceftiofur led to increased phenotypic resistance towards ceftriaxone while its ability to spread the cephalosporin resistance through conjugation, conversely, was impaired.

SIGNIFICANCE AND IMPACT OF THE STUDY

Findings from this study shed light on one possible mechanism in which agricultural cephalosporin exposure in Salmonella may subsequently impact clinical treatment. The finding that cephalosporin exposure in donors may hinder the subsequent spread of resistance instead of aiding it up was counter-intuitive.

摘要

目的

尽管已有研究证明,头孢菌素类药物头孢噻呋与沙门氏菌的耐药性之间存在关联,但这种相关性的潜在机制尚不清楚。本研究旨在探讨头孢噻呋暴露对圣路易斯沙门氏菌头孢曲松耐药性、bla 基因表达和可转移性的影响。

方法与结果

先前头孢噻呋暴露使头孢曲松的 MIC 值从 1024µg/ml 增加至 2048µg/ml,增加了 2 倍;Bla 2·2 酶的活性从 3.46nmol 硝头孢菌素水解/min 增加至 7.67nmol 硝头孢菌素水解/min,增加了 2 倍。bla 基因的表达也上调了 3 倍。暴露于头孢噻呋的供体随后表现出转移效率降低 2.5 倍。

结论

圣路易斯沙门氏菌先前暴露于头孢噻呋会导致对头孢曲松的表型耐药性增加,而其通过接合传播头孢菌素耐药性的能力则受到损害。

研究的意义和影响

本研究结果揭示了农业头孢菌素暴露在沙门氏菌中可能随后影响临床治疗的一种可能机制。供体中头孢菌素暴露可能会阻碍随后的耐药性传播,而不是助长耐药性传播,这一发现有悖常理。

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