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对中间型葡萄球菌中多重耐药性快速出现和演变的基因组学见解。

Genomic insights into the rapid emergence and evolution of MDR in Staphylococcus pseudintermedius.

作者信息

McCarthy Alex J, Harrison Ewan M, Stanczak-Mrozek Kinga, Leggett Bernadette, Waller Andrew, Holmes Mark A, Lloyd David H, Lindsay Jodi A, Loeffler Anette

机构信息

Institute of Infection and Immunity, St George's, University of London, London, UK.

Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

出版信息

J Antimicrob Chemother. 2015 Apr;70(4):997-1007. doi: 10.1093/jac/dku496. Epub 2014 Dec 18.

Abstract

OBJECTIVES

MDR methicillin-resistant Staphylococcus pseudintermedius (MRSP) strains have emerged rapidly as major canine pathogens and present serious treatment issues and concerns to public health due to their, albeit low, zoonotic potential. A further understanding of the genetics of resistance arising from a broadly susceptible background of S. pseudintermedius is needed.

METHODS

We sequenced the genomes of 12 S. pseudintermedius isolates of varied STs and resistance phenotypes.

RESULTS

Nine distinct clonal lineages had acquired either staphylococcal cassette chromosome (SCC) mec elements and/or Tn5405-like elements carrying up to five resistance genes [aphA3, sat, aadE, erm(B), dfrG] to generate MRSP, MDR methicillin-susceptible S. pseudintermedius and MDR MRSP populations. The most successful and clinically problematic MDR MRSP clones, ST68 SCCmecV(T) and ST71 SCCmecII-III, have further accumulated mutations in gyrA and grlA conferring resistance to fluoroquinolones. The carriage of additional mobile genetic elements (MGEs) was highly variable, suggesting that horizontal gene transfer is frequent in S. pseudintermedius populations.

CONCLUSIONS

Importantly, the data suggest that MDR MRSP evolved rapidly by the acquisition of a very limited number of MGEs and mutations, and that the use of many classes of antimicrobials may co-select for the spread and emergence of MDR and XDR strains. Antimicrobial stewardship will need to be comprehensive, encompassing human medicine and veterinary disciplines to successfully preserve antimicrobial efficacy.

摘要

目的

耐甲氧西林中间型葡萄球菌(MRSP)菌株已迅速成为主要的犬类病原体,尽管其人畜共患病潜力较低,但仍给公共卫生带来严重的治疗问题和担忧。需要进一步了解源自中间型葡萄球菌广泛敏感背景的耐药遗传学。

方法

我们对12株不同序列类型(STs)和耐药表型的中间型葡萄球菌分离株进行了全基因组测序。

结果

9个不同的克隆谱系获得了葡萄球菌盒式染色体(SCC)mec元件和/或携带多达5个耐药基因[aphA3、sat、aadE、erm(B)、dfrG]的Tn5405样元件,以产生MRSP、耐甲氧西林敏感的多重耐药中间型葡萄球菌和多重耐药MRSP群体。最成功且临床上最成问题的多重耐药MRSP克隆,即ST68 SCCmecV(T)和ST71 SCCmecII-III,在gyrA和grlA中进一步积累了突变,赋予对氟喹诺酮类药物的耐药性。其他移动遗传元件(MGEs)的携带情况高度可变,表明水平基因转移在中间型葡萄球菌群体中很常见。

结论

重要的是,数据表明多重耐药MRSP通过获得非常有限数量的MGEs和突变而迅速进化,并且使用多种类别的抗菌药物可能会共同选择多重耐药和广泛耐药菌株的传播和出现。抗菌药物管理需要全面,涵盖人类医学和兽医学科,以成功保持抗菌疗效。

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