Evolutionary Responses to Acquiring a Multidrug Resistance Plasmid Are Dominated by Metabolic Functions across Diverse Escherichia coli Lineages.
Evolutionary Responses to Acquiring a Multidrug Resistance Plasmid Are Dominated by Metabolic Functions across Diverse Escherichia coli Lineages.
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DOI：
10.1128/msystems.00713-22
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发表时间：
2023-02-23
期刊：
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
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多药耐药（MDR）质粒驱动细菌谱系之间抗生素耐药性的传播。MDR质粒获得对适应性和细胞过程的直接影响在细菌谱系中各不相同，但使MDR质粒的基因组整合的进化过程如何变化还不太清楚，特别是在临床病原体中。使用不同的大肠杆菌谱系实验进化了约700代，我们表明，获得MDR质粒pLL 35的进化反应是由影响代谢和调控功能的染色体突变主导的，具有菌株特异性和共享的突变靶点。已知这些功能中的几种的表达，例如厌氧代谢，在获得pLL 35后改变。与居民的移动的遗传元件，特别是几个IS元件，相互作用，加强平行突变，包括插入上游的hns，与其上调和下调的质粒编码的超广谱β-内酰胺酶基因。质粒平行突变靶向接合相关基因，其表达在进化克隆中也通常下调。除了在水平基因转移中的作用之外，质粒还可以成为塑造细菌染色体和核心细胞功能进化的重要选择力。重要性质粒驱动细菌基因组之间的抗菌素耐药基因的传播。然而，允许质粒被不同细菌基因组同化的进化过程知之甚少，特别是在临床病原体中。使用不同的E.大肠杆菌谱系和临床多药耐药质粒，我们表明，虽然质粒驱动每个谱系独特的进化路径，有一个令人惊讶的程度的收敛，在跨谱系的突变，代谢功能为主的目标功能。值得注意的是，这些相同的代谢功能在自然界中的MDR谱系中显示出更高的进化速率，并且在某些情况下，如厌氧代谢，它们的表达直接由质粒操纵。与基因组中其他移动的元素的相互作用通过破坏它们插入的基因和调节序列来加速适应。除了它们在水平基因转移中的作用外，质粒是驱动细菌基因组和核心细胞功能进化的重要选择力。
Multidrug resistance (MDR) plasmids drive the spread of antibiotic resistance between bacterial lineages. The immediate impact of MDR plasmid acquisition on fitness and cellular processes varies among bacterial lineages, but how the evolutionary processes enabling the genomic integration of MDR plasmids vary is less well understood, particularly in clinical pathogens. Using diverse Escherichia coli lineages experimentally evolved for ~700 generations, we show that the evolutionary response to gaining the MDR plasmid pLL35 was dominated by chromosomal mutations affecting metabolic and regulatory functions, with both strain-specific and shared mutational targets. The expression of several of these functions, such as anaerobic metabolism, is known to be altered upon acquisition of pLL35. Interactions with resident mobile genetic elements, notably several IS-elements, potentiated parallel mutations, including insertions upstream of hns that were associated with its upregulation and the downregulation of the plasmid-encoded extended-spectrum beta-lactamase gene. Plasmid parallel mutations targeted conjugation-related genes, whose expression was also commonly downregulated in evolved clones. Beyond their role in horizontal gene transfer, plasmids can be an important selective force shaping the evolution of bacterial chromosomes and core cellular functions. IMPORTANCE Plasmids drive the spread of antimicrobial resistance genes between bacterial genomes. However, the evolutionary processes allowing plasmids to be assimilated by diverse bacterial genomes are poorly understood, especially in clinical pathogens. Using experimental evolution with diverse E. coli lineages and a clinical multidrug resistance plasmid, we show that although plasmids drove unique evolutionary paths per lineage, there was a surprising degree of convergence in the functions targeted by mutations across lineages, dominated by metabolic functions. Remarkably, these same metabolic functions show higher evolutionary rates in MDR-lineages in nature and in some cases, like anaerobic metabolism, their expression is directly manipulated by the plasmid. Interactions with other mobile elements resident in the genomes accelerated adaptation by disrupting genes and regulatory sequences that they inserted into. Beyond their role in horizontal gene transfer, plasmids are an important selective force driving the evolution of bacterial genomes and core cellular functions.
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影响因子：
16.8
作者：
Jordt H;Stalder T;Kosterlitz O;Ponciano JM;Top EM;Kerr B
通讯作者：
Kerr B
影响因子：
16.8
作者：
Bottery MJ;Wood AJ;Brockhurst MA
通讯作者：
Brockhurst MA
DOI：
10.1038/s41396-021-00926-w
发表时间：
2021-08
期刊：
The ISME journal
影响因子：
--
作者：
Matlock W;Chau KK;AbuOun M;Stubberfield E;Barker L;Kavanagh J;Pickford H;Gilson D;Smith RP;Gweon HS;Hoosdally SJ;Swann J;Sebra R;Bailey MJ;Peto TEA;Crook DW;Anjum MF;Read DS;Walker AS;Stoesser N;Shaw LP;REHAB consortium
通讯作者：
REHAB consortium
DOI：
10.1038/s41396-018-0276-9
发表时间：
2019-03
期刊：
The ISME journal
影响因子：
--
作者：
Bottery MJ;Wood AJ;Brockhurst MA
通讯作者：
Brockhurst MA
影响因子：
16.8
作者：
Loftie-Eaton W;Bashford K;Quinn H;Dong K;Millstein J;Hunter S;Thomason MK;Merrikh H;Ponciano JM;Top EM
通讯作者：
Top EM