The Proteus mirabilis PmirS clinical isolate, which was susceptible to imipenem (0.5 μg/mL) and amikacin (1 μg/mL), was recovered from a bronchial aspirate of a patient who recently underwent lung transplantation. The P. mirabilis PmirR clinical isolate, which exhibited resistance to imipenem (16 μg/mL) and amikacin (24 μg/mL), was isolated 3 weeks later from the same patient and the same specimen type. Using short-read sequencing technology, these isolates appeared to be genetically identical except the cpxA gene of the PmirR isolate that was mutated leading to the His-208-Pro substitution. The structural alteration was localized in the histidine kinase, adenylate cyclase, methyl accepting protein, phosphatase (HAMP) domain, which is involved in the signal transduction between the sensor kinase and the regulator response of the CpxA/CpxR two-component system (TCS). No significant defect in the growth rate was found between the PmirS and PmirR isolates. This study suggests that alteration in CpxA might confer imipenem and amikacin resistance in P. mirabilis. This study brings new evidence that the TCS alteration could provide an adaptive capacity in a clinical context by conferring antibiotic resistance without fitness cost.

中文翻译：

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在产生 CpxA-H208P 变体的奇异变形杆菌临床分离株中出现亚胺培南抗性

的奇异变形杆菌PmirS临床分离株，这是容易受到亚胺培南（0.5微克/毫升）和丁胺卡那霉素（1微克/毫升）中，从患者谁最近进行肺移植的支气管吸回收。的奇异变形杆菌PmirR临床分离物，其显示对亚胺培南（16微克/毫升）和丁胺卡那霉素抗性（24微克/毫升）中，来自同一患者，并且在同一标本类型分离3周后。使用短读长测序技术，除了cpxA之外，这些分离株似乎在基因上是相同的PmirR 分离株的基因突变导致 His-208-Pro 取代。结构改变位于组氨酸激酶、腺苷酸环化酶、甲基接受蛋白、磷酸酶 (HAMP) 域中，参与传感器激酶之间的信号转导和 CpxA/CpxR 双组分系统 (TCS) 的调节响应. 在 PmirS 和 PmirR 分离株之间没有发现显着的生长速度缺陷。这项研究表明，CpxA 的改变可能会导致奇异变形杆菌对亚胺培南和阿米卡星产生抗性。这项研究带来了新的证据，表明 TCS 改变可以通过赋予抗生素抗性而无需健身成本来提供临床环境中的适应能力。