Research ArticleMicrobiology

Signaling by two-component system noncognate partners promotes intrinsic tolerance to polymyxin B in uropathogenic Escherichia coli

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Sci. Signal.  10 Jan 2017:
Vol. 10, Issue 461, eaag1775
DOI: 10.1126/scisignal.aag1775

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Unusual signaling partners

Bacteria use two-component systems to sense and respond to environmental stimuli. Each two-component system consists of a sensor histidine kinase and a response regulator. Most sensors and response regulators function as exclusive partners (cognate partners) that do not interact with components of other two-component systems. Guckes and Breland et al. studied the response of a strain of uropathogenic Escherichia coli to iron, an ion representative of the cations that bacteria encounter during infection. Exposing these bacteria to ferric iron stimulated the histidine kinase PmrB to phosphorylate its cognate response regulator PmrA and the noncognate response regulator QseB, both of which were required for the transcriptional response to ferric iron. Pretreating clinical isolates of uropathogenic E. coli with iron increased the tolerance of some strains to the antibiotic polymyxin B. This study identifies an example of signaling through noncognate interactions between two-component systems and implicates both cognate and noncognate signaling by PmrB in antibiotic resistance of some uropathogenic strains of E. coli.

Abstract

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.

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