title: Proteomic analysis of iron acquisition, metabolic and regulatory responses of Yersinia pestis to iron starvation.
abstract: BACKGROUND
  The Gram-negative bacterium Yersinia pestis is the causative agent of the bubonic plague. Efficient iron acquisition systems are critical to the ability of Y. pestis to infect, spread and grow in mammalian hosts, because iron is sequestered and is considered part of the innate host immune defence against invading pathogens. We used a proteomic approach to determine expression changes of iron uptake systems and intracellular consequences of iron deficiency in the Y. pestis strain KIM6+ at two physiologically relevant temperatures (26 degrees C and 37 degrees C).
  
  
  RESULTS
  Differential protein display was performed for three Y. pestis subcellular fractions. Five characterized Y. pestis iron/siderophore acquisition systems (Ybt, Yfe, Yfu, Yiu and Hmu) and a putative iron/chelate outer membrane receptor (Y0850) were increased in abundance in iron-starved cells. The iron-sulfur (Fe-S) cluster assembly system Suf, adapted to oxidative stress and iron starvation in E. coli, was also more abundant, suggesting functional activity of Suf in Y. pestis under iron-limiting conditions. Metabolic and reactive oxygen-deactivating enzymes dependent on Fe-S clusters or other iron cofactors were decreased in abundance in iron-depleted cells. This data was consistent with lower activities of aconitase and catalase in iron-starved vs. iron-rich cells. In contrast, pyruvate oxidase B which metabolizes pyruvate via electron transfer to ubiquinone-8 for direct utilization in the respiratory chain was strongly increased in abundance and activity in iron-depleted cells.
  
  
  CONCLUSIONS
  Many protein abundance differences were indicative of the important regulatory role of the ferric uptake regulator Fur. Iron deficiency seems to result in a coordinated shift from iron-utilizing to iron-independent biochemical pathways in the cytoplasm of Y. pestis. With growth temperature as an additional variable in proteomic comparisons of the Y. pestis fractions (26 degrees C and 37 degrees C), there was little evidence for temperature-specific adaptation processes to iron starvation.
authors.affiliation: J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA. rpieper@jcvi.org
authors.forename: Rembert
authors.initials: R
authors.lastname: Pieper
authors.forename: Shih-Ting
authors.initials: ST
authors.lastname: Huang
authors.forename: Prashanth P
authors.initials: PP
authors.lastname: Parmar
authors.forename: David J
authors.initials: DJ
authors.lastname: Clark
authors.forename: Hamid
authors.initials: H
authors.lastname: Alami
authors.forename: Robert D
authors.initials: RD
authors.lastname: Fleischmann
authors.forename: Robert D
authors.initials: RD
authors.lastname: Perry
authors.forename: Scott N
authors.initials: SN
authors.lastname: Peterson
mesh_terms: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005290:Ferric Compounds / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D033902:Periplasmic Binding Proteins; D040901:Proteomics / Q000379:methods; D013347:Subcellular Fractions / Q000737:chemistry; D015010:Yersinia pestis / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D005290:Ferric Compounds; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D033902:Periplasmic Binding Proteins; C427026:Yfu protein, Yersinia; D007501:Iron