Guckes Kirsten R, Breland Erin J, Zhang Ellisa W, Hanks Sarah C, Gill Navleen K, Algood Holly M S, Schmitz Jonathan E, Stratton Charles W, Hadjifrangiskou Maria
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Sci Signal. 2017 Jan 10;10(461):eaag1775. doi: 10.1126/scisignal.aag1775.
Bacteria use two-component systems (TCSs) to react appropriately to environmental stimuli. Typical TCSs comprise a sensor histidine kinase that acts as a receptor coupled to a partner response regulator that coordinates changes in bacterial behavior, often through its activity as a transcriptional regulator. TCS interactions are typically confined to cognate pairs of histidine kinases and response regulators. We describe two distinct TCSs in uropathogenic Escherichia coli (UPEC) that interact to mediate a response to ferric iron. The PmrAB and QseBC TCSs were both required for proper transcriptional response to ferric iron. Ferric iron induced the histidine kinase PmrB to phosphotransfer to both its cognate response regulator PmrA and the noncognate response regulator QseB, leading to transcriptional responses coordinated by both regulators. Pretreatment of the UPEC strain UTI89 with ferric iron led to increased resistance to polymyxin B that required both PmrA and QseB. Similarly, pretreatment of several UPEC isolates with ferric iron increased tolerance to polymyxin B. This study defines physiologically relevant cross talk between TCSs in a bacterial pathogen and provides a potential mechanism for antibiotic resistance of some strains of UPEC.
细菌利用双组分系统（TCSs）来对环境刺激做出适当反应。典型的双组分系统包括一个传感组氨酸激酶，它作为受体与一个伴侣反应调节因子偶联，该反应调节因子通常通过作为转录调节因子的活性来协调细菌行为的变化。双组分系统的相互作用通常局限于组氨酸激酶和反应调节因子的同源对。我们描述了尿路致病性大肠杆菌（UPEC）中两种不同的双组分系统，它们相互作用以介导对三价铁的反应。PmrAB和QseBC双组分系统对于对三价铁的适当转录反应都是必需的。三价铁诱导组氨酸激酶PmrB将磷酸基团转移至其同源反应调节因子PmrA和非同源反应调节因子QseB，从而导致由这两种调节因子协调的转录反应。用三价铁预处理尿路致病性大肠杆菌菌株UTI89会导致对多粘菌素B的抗性增加，这需要PmrA和QseB两者。同样，用三价铁预处理几种尿路致病性大肠杆菌分离株会增加对多粘菌素B的耐受性。这项研究定义了细菌病原体中双组分系统之间生理上相关的串扰，并为某些尿路致病性大肠杆菌菌株的抗生素抗性提供了一种潜在机制。
