title: Genome-wide analysis of the response to nitric oxide in uropathogenicEscherichia coliCFT073.
abstract: UropathogenicEscherchia coli(UPEC) is the causative agent of urinary tract infections. Nitric oxide (NO) is a toxic water-soluble gas that is encountered by UPEC in the urinary tract. Therefore, UPEC probably requires mechanisms to detoxify NO in the host environment. Thus far, flavohaemoglobin (Hmp), an NO denitrosylase, is the only demonstrated NO detoxification system in UPEC. Here we show that, inE. colistrain CFT073, the NADH-dependent NO reductase flavorubredoxin (FlRd) also plays a major role in NO scavenging. We generated a mutant that lacks all known and candidate NO detoxification pathways (Hmp, FlRd and the respiratory nitrite reductase, NrfA). When grown and assayed anaerobically, this mutant expresses an NO-inducible NO scavenging activity, pointing to the existence of a novel detoxification mechanism. Expression of this activity is inducible by both NO and nitrate, and the enzyme is membrane-associated. Genome-wide transcriptional profiling of UPEC grown under anaerobic conditions in the presence of nitrate (as a source of NO) highlighted various aspects of the response of the pathogen to nitrate and NO. Several virulence-associated genes are upregulated, suggesting that host-derived NO is a potential regulator of UPEC virulence. Chromatin immunoprecipitation and sequencing was used to evaluate the NsrR regulon in CFT073. We identified 49 NsrR binding sites in promoter regions in the CFT073 genome, 29 of which were not previously identified inE. coliK-12. NsrR may regulate some CFT073 genes that do not have homologues inE. coliK-12.
authors.affiliation: Department of Biological Sciences, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA.
authors.forename: Heer H
authors.initials: HH
authors.lastname: Mehta
authors.affiliation: Department of Biological Sciences, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA.|Center for Systems Biology, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Systems Biology, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA.|Department of Biological Sciences, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA.
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Spiro
keywords: ChIP-seq; NsrR; RNA-seq; nitric oxide; uropathogenic E. coli