Limited and Strain-Specific Transcriptional and Growth Responses to Acquisition of a Multidrug Resistance Plasmid in Genetically Diverse Escherichia coli Lineages.
Limited and Strain-Specific Transcriptional and Growth Responses to Acquisition of a Multidrug Resistance Plasmid in Genetically Diverse Escherichia coli Lineages.
复制标题
有限和菌株特异性转录和生长反应收购多药耐药质粒在遗传多样性大肠杆菌谱系。
DOI：
10.1128/msystems.00083-21
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发表时间：
2021-04-27
期刊：
影响因子：
6.4
通讯作者：
McNally A
中科院分区：
文献类型：
--
作者：
Dunn S;Carrilero L;Brockhurst M;McNally A
质粒通过在谱系之间转移适应性功能在细菌进化中发挥关键作用，这些功能通常能够入侵新的生态位，包括驱动抗生素抗性基因的传播。由于细胞过程的破坏而产生的质粒获取的适应性成本可以限制多药耐药质粒的传播。多药耐药（MDR）大肠杆菌菌株是对人类健康的主要全球性威胁，其中多药耐药性主要通过MDR质粒获得传播。MDR质粒在整个大肠杆菌中的分布并不广泛。大肠杆菌物种，而是集中在少数克隆。在这里，我们测试，如果不同的E。大肠杆菌菌株获得和维持MDR质粒的能力不同，这是否与质粒获得后的转录反应有关。我们使用了来自E.大肠杆菌菌株，包括常见的MDR谱系序列类型131（ST 131）和IncF质粒pLL 35，携带多个抗生素抗性基因。菌株通过接合获得pLL 35的能力各不相同，但所有菌株都能够稳定地维持质粒。pLL 35收购头孢噻肟耐药性和生长的影响也各不相同的菌株，与生长反应范围从一个小的减少到一个小的增加，相对于亲本菌株的质粒载体的增长。对pLL35获取的转录应答在规模上是有限的并且是高度菌株特异性的。我们观察到操纵子或调节子水平的转录反应可能是由于应激反应或与居民移动的遗传元件（MGE）的相互作用。观察到所有菌株之间一致的微妙的转录反应影响功能，如厌氧代谢，先前显示在MDR E中处于负频率依赖性选择下。杆菌总体而言，菌株间转录和生长反应的幅度之间没有相关性。总之，这些数据表明，转录破坏产生的适应性成本不太可能成为该MDR质粒在大肠杆菌中传播的障碍。杆菌重要性质粒通过在谱系之间转移适应性功能在细菌进化中发挥关键作用，这些功能通常能够入侵新的生态位，包括驱动抗生素抗性基因的传播。由于细胞过程的破坏而产生的质粒获取的适应性成本可以限制多药耐药质粒的传播。然而，质粒获取的影响通常在实验室适应的菌株而不是天然分离株中测量，天然分离株充当维持质粒并将其传递至临床相关菌株的储存库。使用临床多药耐药质粒和多种E.从临床感染和自然环境中分离的大肠杆菌菌株，我们表明，在实验室条件下，质粒收购细菌的生长和转录只有有限的和高度菌株特异性的影响。这些发现表明，转录破坏引起的适应性成本不太可能成为该质粒在大肠杆菌自然群体中传播的障碍。杆菌
Plasmids play a key role in bacterial evolution by transferring adaptive functions between lineages that often enable invasion of new niches, including driving the spread of antibiotic resistance genes. Fitness costs of plasmid acquisition arising from the disruption of cellular processes could limit the spread of multidrug resistance plasmids. Multidrug-resistant (MDR) Escherichia coli strains are a major global threat to human health, wherein multidrug resistance is primarily spread by MDR plasmid acquisition. MDR plasmids are not widely distributed across the entire E. coli species, but instead are concentrated in a small number of clones. Here, we test if diverse E. coli strains vary in their ability to acquire and maintain MDR plasmids and if this relates to their transcriptional response following plasmid acquisition. We used strains from across the diversity of E. coli strains, including the common MDR lineage sequence type 131 (ST131) and the IncF plasmid pLL35, carrying multiple antibiotic resistance genes. Strains varied in their ability to acquire pLL35 by conjugation, but all were able to stably maintain the plasmid. The effects of pLL35 acquisition on cefotaxime resistance and growth also varied among strains, with growth responses ranging from a small decrease to a small increase in growth of the plasmid carrier relative to the parental strain. Transcriptional responses to pLL35 acquisition were limited in scale and highly strain specific. We observed transcriptional responses at the operon or regulon level—possibly due to stress responses or interactions with resident mobile genetic elements (MGEs). Subtle transcriptional responses consistent across all strains were observed affecting functions, such as anaerobic metabolism, previously shown to be under negative frequency-dependent selection in MDR E. coli. Overall, there was no correlation between the magnitudes of the transcriptional and growth responses across strains. Together, these data suggest that fitness costs arising from transcriptional disruption are unlikely to act as a barrier to dissemination of this MDR plasmid in E. coli. IMPORTANCE Plasmids play a key role in bacterial evolution by transferring adaptive functions between lineages that often enable invasion of new niches, including driving the spread of antibiotic resistance genes. Fitness costs of plasmid acquisition arising from the disruption of cellular processes could limit the spread of multidrug resistance plasmids. However, the impacts of plasmid acquisition are typically measured in lab-adapted strains rather than natural isolates, which act as reservoirs for the maintenance and transmission of plasmids to clinically relevant strains. Using a clinical multidrug resistance plasmid and a diverse collection of E. coli strains isolated from clinical infections and natural environments, we show that plasmid acquisition had only limited and highly strain-specific effects on bacterial growth and transcription under laboratory conditions. These findings suggest that fitness costs arising from transcriptional disruption are unlikely to act as a barrier to transmission of this plasmid in natural populations of E. coli.