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Sci Signal. 2017 Jan 10;10(461). pii: eaag1775. doi: 10.1126/scisignal.aag1775.

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

Author information

1
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
2
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
3
Barnard College, New York, NY 10027, USA.
4
Vanderbilt University, Nashville, TN 37240, USA.
5
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
6
Veterans Affairs Tennessee Valley Healthcare Services, Nashville, TN 37212, USA.
7
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. maria.hadjifrangiskou@vanderbilt.edu.
8
Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

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.

PMID:
28074004
PMCID:
PMC5677524
DOI:
10.1126/scisignal.aag1775
[Indexed for MEDLINE]
Free PMC Article

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