Multi-drug resistant (MDR) Escherichia coli are a major global threat to human health, wherein multi-drug 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, including the common MDR lineage ST131, and the IncF plasmid, pLL35, encoding 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 significant transcriptional responses at the operon or regulon level, possibly due to stress responses or interactions with resident 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 magnitude 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.

中文翻译：

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在遗传多样的大肠杆菌谱系中获得多药抗性质粒的有限和菌株特异性转录和生长反应

多药耐药性（MDR）大肠杆菌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质粒的获得而传播。MDR质粒没有广泛分布在整个大肠杆菌中，而是集中在少数克隆中。在这里，我们测试了不同的大肠杆菌菌株在获取和维持MDR质粒的能力上是否有所不同，以及这是否与质粒获取后它们的转录反应有关。我们使用了来自大肠杆菌多样性的菌株，包括常见的MDR谱系ST131和编码多个抗生素抗性基因的IncF质粒pLL35。菌株通过缀合获得pLL35的能力各不相同，但是所有菌株都能稳定地维持质粒。pLL35采集对头孢噻肟抗性和生长的影响在菌株之间也有所不同，相对于亲代菌株，质粒载体的生长响应范围从小幅下降到小幅增长。对pLL35采集的转录反应在规模和高度菌株特异性方面受到限制。我们观察到在操纵子或调节子水平的重大转录反应，可能是由于应激反应或与居民MGE的相互作用。观察到在所有菌株中一致的微妙的转录反应影响了功能，例如厌氧代谢，以前显示在MDR大肠杆菌中处于负频率依赖性选择下。总体而言，跨菌株的转录和生长反应的幅度之间没有相关性。