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在研究用猕猴体内植入设备中长期定植粪肠球菌的动态。

Long-Term Colonization Dynamics of Enterococcus faecalis in Implanted Devices in Research Macaques.

机构信息

Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

出版信息

Appl Environ Microbiol. 2018 Aug 31;84(18). doi: 10.1128/AEM.01336-18. Print 2018 Sep 15.

Abstract

is a common opportunistic pathogen that colonizes cephalic recording chambers (CRCs) of macaques used in cognitive neuroscience research. We previously characterized 15 strains isolated from macaques at the Massachusetts Institute of Technology (MIT) in 2011. The goal of this study was to examine how a 2014 protocol change prohibiting the use of antimicrobials within CRCs affected colonizing strains. We collected 20 isolates from 10 macaques between 2013 and 2017 for comparison to 4 isolates previously characterized in 2011 with respect to the sequence type (ST) distribution, antimicrobial resistance, biofilm formation, and changes in genes that might confer a survival advantage. ST4 and ST55 were predominant among the isolates characterized in 2011, whereas the less antimicrobial-resistant lineage ST48 emerged to dominance after 2013. Two macaques remained colonized by ST4 and ST55 strains for 5 and 4 years, respectively. While the antimicrobial resistance and virulence factors identified in these ST4 and ST55 strains remained relatively stable, we detected an increase in biofilm formation ability over time in both isolates. We also found that ST48 strains were typically robust biofilm formers, which could explain why this ST increased in prevalence. Finally, we identified mutations in the DNA mismatch repair genes and in separate ST55 and ST4 strains and confirmed that strains bearing these mutations displayed a hypermutator phenotype. The presence of a hypermutator phenotype may complicate future antimicrobial treatment for clinically relevant infections in macaques. is a common cause of health care-associated infections in humans, largely due to its ability to persist in the hospital environment, colonize patients, acquire antimicrobial resistance, and form biofilms. Understanding how enterococci evolve in health care settings provides insight into factors affecting enterococcal survival and persistence. Macaques used in neuroscience research have long-term cranial implants that, despite best practices, often become colonized by This provides a unique opportunity to noninvasively examine the evolution of enterococci on a long-term indwelling device. We collected strains from cephalic implants over a 7-year period and characterized the sequence type, antimicrobial resistance, virulence factors, biofilm production, and hypermutator phenotypes. Improved antimicrobial stewardship allowed a less-antimicrobial-resistant strain to predominate at the implant interface, potentially improving antimicrobial treatment outcomes if future clinical infections occur. Biofilm formation appears to play an important role in the persistence of the strains associated with these implants.

摘要

是一种常见的机会性病原体,定植于用于认知神经科学研究的猕猴的头状记录腔(CRC)。我们之前于 2011 年从麻省理工学院(MIT)的猕猴中分离出 15 株。本研究的目的是研究 2014 年禁止在 CRC 中使用抗菌药物的方案改变如何影响定植菌株。我们从 2013 年至 2017 年期间的 10 只猕猴中收集了 20 个分离株,与之前于 2011 年分离出的 4 个分离株进行比较,涉及序列型(ST)分布、抗菌药物耐药性、生物膜形成以及可能赋予生存优势的基因变化。2011 年分离出的菌株中,ST4 和 ST55 占主导地位,而耐药性较低的 ST48 谱系在 2013 年后占主导地位。两只猕猴分别有 ST4 和 ST55 菌株定植 5 年和 4 年。虽然这些 ST4 和 ST55 菌株的抗菌药物耐药性和毒力因子相对稳定,但我们发现生物膜形成能力随时间增加。我们还发现 ST48 菌株通常是强大的生物膜形成者,这可以解释为什么该 ST 增加了流行率。最后,我们在单独的 ST55 和 ST4 菌株中发现了 DNA 错配修复基因 和 的突变,并证实携带这些突变的菌株表现出超突变表型。超突变表型的存在可能使未来针对猕猴中临床相关 感染的抗菌药物治疗复杂化。是人类医疗保健相关感染的常见病因,主要是因为它能够在医院环境中存活、定植于患者、获得抗菌药物耐药性并形成生物膜。了解 enterococci 在医疗保健环境中的进化情况可为影响 enterococci 生存和持久性的因素提供深入了解。用于神经科学研究的猕猴具有长期的颅内置物,尽管采用了最佳实践,但这些植入物经常被 定植。这为非侵入性地研究长期留置装置上的 enterococci 进化提供了独特的机会。我们在 7 年期间从头状植入物中收集了 株,并对序列型、抗菌药物耐药性、毒力因子、生物膜形成和超突变表型进行了表征。改善抗菌药物管理允许一种耐药性较低的 菌株在植入物界面占主导地位,如果未来发生临床感染,这可能会改善抗菌药物治疗效果。生物膜形成似乎在与这些植入物相关的 菌株的持久性中发挥了重要作用。

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