title: Signaling by two-component system noncognate partners promotes intrinsic tolerance to polymyxin B in uropathogenic Escherichia 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.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Kirsten R
authors.initials: KR
authors.lastname: Guckes
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Breland
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Ellisa W
authors.initials: EW
authors.lastname: Zhang
authors.affiliation: Barnard College, New York, NY 10027, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Hanks
authors.affiliation: Vanderbilt University, Nashville, TN 37240, USA.
authors.forename: Navleen K
authors.initials: NK
authors.lastname: Gill
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.|Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.|Veterans Affairs Tennessee Valley Healthcare Services, Nashville, TN 37212, USA.
authors.forename: Holly M S
authors.initials: HM
authors.lastname: Algood
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Schmitz
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.|Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Stratton
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. maria.hadjifrangiskou@vanderbilt.edu.|Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Hadjifrangiskou
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004361:Drug Tolerance / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D005290:Ferric Compounds / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D007477:Ions / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D056689:Uropathogenic Escherichia coli / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D005290:Ferric Compounds; D007477:Ions; C409039:PmrB protein, bacteria; C455503:QseB protein, E coli; C455504:QseC protein, E coli; D014157:Transcription Factors; C081902:pmrA protein, Bacteria; D011112:Polymyxin B