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亚致死剂量环丙沙星诱导的诱变:PA14菌株与临床分离株之间的基因型和表型差异

Mutagenesis Induced by Sub-Lethal Doses of Ciprofloxacin: Genotypic and Phenotypic Differences Between the Strain PA14 and Clinical Isolates.

作者信息

Migliorini Letícia Busato, Brüggemann Holger, de Sales Romario Oliveira, Koga Paula Célia Mariko, de Souza Andrea Vieira, Martino Marines Dalla Valle, Galhardo Rodrigo S, Severino Patricia

机构信息

Hospital Israelita Albert Einstein, Albert Einstein Research and Education Institute, São Paulo, Brazil.

Department of Biomedicine, Aarhus University, Aarhus, Denmark.

出版信息

Front Microbiol. 2019 Jul 10;10:1553. doi: 10.3389/fmicb.2019.01553. eCollection 2019.

Abstract

Bacterial resistance is a severe threat to global public health. Exposure to sub-lethal concentrations has been considered a major driver of mutagenesis leading to antibiotic resistance in clinical settings. Ciprofloxacin is broadly used to treat infections caused by , whereas increased mutagenesis induced by sub-lethal concentrations of ciprofloxacin has been reported for the reference strain, PAO1, . In this study we report increased mutagenesis induced by sub-lethal concentrations of ciprofloxacin for another reference strain, PA14-UCBPP, and lower mutagenesis for clinical isolates when compared to the reference strain. This unexpected result may be associated with missense mutations in and , involved in adaptive responses, and the presence of Pyocin S2, which were found in all clinical isolates but not in the reference strain genome. The genetic differences between clinical isolates of and the reference PA14-UCBPP, often used to study phenotypes , may be involved in reduced mutagenesis under sub-lethal concentrations of CIP, a scenario that should be further explored for the understanding of bacterial fitness in hospital environments. Moreover, we highlight the presence of a complete operon in a clinical isolate. Even though the presence of did not contribute to a significant increase in mutagenesis, it highlights the dynamic exchange of genetic material between bacterial species in the hospital environment.

摘要

细菌耐药性是对全球公共卫生的严重威胁。暴露于亚致死浓度被认为是导致临床环境中抗生素耐药性的诱变的主要驱动因素。环丙沙星广泛用于治疗由……引起的感染,而对于参考菌株PAO1,已报道亚致死浓度的环丙沙星会诱导诱变增加。在本研究中,我们报告了亚致死浓度的环丙沙星对另一个参考菌株PA14-UCBPP诱导的诱变增加,并且与参考菌株相比,临床分离株的诱变较低。这一意外结果可能与参与适应性反应的……中的错义突变以及临床分离株中均存在但参考菌株基因组中不存在的绿脓菌素S2有关。临床分离株与常用于研究……表型的参考PA14-UCBPP之间的遗传差异,可能与亚致死浓度的环丙沙星下诱变减少有关,这种情况应进一步探索以了解医院环境中的细菌适应性。此外,我们强调了在一个……临床分离株中存在完整的……操纵子。尽管……的存在并未导致诱变显著增加,但它突出了医院环境中细菌物种之间遗传物质的动态交换。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b85/6636244/ae773fc7f5a2/fmicb-10-01553-g001.jpg

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