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抗生素和噬菌体共选择作用下细菌群体的基因组进化

Genomic evolution of bacterial populations under coselection by antibiotics and phage.

作者信息

Cairns Johannes, Frickel Jens, Jalasvuori Matti, Hiltunen Teppo, Becks Lutz

机构信息

Department of Food and Environmental Sciences / Microbiology and Biotechnology, University of Helsinki, P.O. Box 65, 00014, Helsinki, Finland.

Department of Evolutionary Ecology / Community Dynamics Group, Max Planck Institute for Evolutionary Biology, August Thienemann Street 2, 24306, Plön, Germany.

出版信息

Mol Ecol. 2017 Apr;26(7):1848-1859. doi: 10.1111/mec.13950. Epub 2017 Jan 6.

DOI:10.1111/mec.13950
PMID:27977892
Abstract

Bacteria live in dynamic systems where selection pressures can alter rapidly, forcing adaptation to the prevailing conditions. In particular, bacteriophages and antibiotics of anthropogenic origin are major bacterial stressors in many environments. We previously observed that populations of the bacterium Pseudomonas fluorescens SBW25 exposed to the lytic bacteriophage SBW25Φ2 and a noninhibitive concentration of the antibiotic streptomycin (coselection) achieved higher levels of phage resistance compared to populations exposed to the phage alone. In addition, the phage became extinct under coselection while remaining present in the phage alone environment. Further, phenotypic tests indicated that these observations might be associated with increased mutation rate under coselection. In this study, we examined the genetic causes behind these phenotypes by whole-genome sequencing clones isolated from the end of the experiments. We were able to identify genetic factors likely responsible for streptomycin resistance, phage resistance and hypermutable (mutator) phenotypes. This constitutes genomic evidence in support of the observation that while the presence of phage did not affect antibiotic resistance, the presence of antibiotic affected phage resistance. We had previously hypothesized an association between mutators and elevated levels of phage resistance under coselection. However, our evidence regarding the mechanism was inconclusive, as although with phage mutators were only found under coselection, additional genomic evidence was lacking and phage resistance was also observed in nonmutators under coselection. More generally, our study provides novel insights into evolution between univariate and multivariate selection (here two stressors), as well as the potential role of hypermutability in natural communities.

摘要

细菌生活在动态系统中,其中选择压力可能迅速改变,迫使细菌适应当前环境。特别是,人为来源的噬菌体和抗生素是许多环境中的主要细菌应激源。我们之前观察到,与仅暴露于噬菌体的群体相比,暴露于裂解性噬菌体SBW25Φ2和非抑制浓度抗生素链霉素(共选择)的荧光假单胞菌SBW25群体获得了更高水平的噬菌体抗性。此外,在共选择条件下噬菌体灭绝,而在仅存在噬菌体的环境中仍然存在。此外,表型测试表明,这些观察结果可能与共选择条件下突变率增加有关。在本研究中,我们通过对实验结束时分离的克隆进行全基因组测序,研究了这些表型背后的遗传原因。我们能够鉴定出可能导致链霉素抗性、噬菌体抗性和高突变(突变体)表型的遗传因素。这构成了基因组证据,支持了噬菌体的存在不影响抗生素抗性,但抗生素的存在影响噬菌体抗性这一观察结果。我们之前曾假设突变体与共选择条件下噬菌体抗性水平升高之间存在关联。然而,我们关于机制的证据并不确凿,因为虽然仅在共选择条件下发现了带有噬菌体的突变体,但缺乏额外的基因组证据,并且在共选择条件下非突变体中也观察到了噬菌体抗性。更普遍地说,我们的研究为单变量和多变量选择(这里是两种应激源)之间的进化以及高突变性在自然群落中的潜在作用提供了新的见解。

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