Proteomic analysis of iron acquisition, metabolic and regulatory responses of <it>Yersinia pestis </it>to iron starvation

• Main Authors: Fleischmann Robert D, Alami Hamid, Clark David J, Parmar Prashanth P, Huang Shih-Ting, Pieper Rembert, Perry Robert D, Peterson Scott N
• Format: Article
• Language: English
• Published: BMC 2010-01-01
• Series: BMC Microbiology
• Online Access: http://www.biomedcentral.com/1471-2180/10/30

<p>Abstract</p> <p>Background</p> <p>The Gram-negative bacterium <it>Yersinia pestis </it>is the causative agent of the bubonic plague. Efficient iron acquisition systems are critical to the ability of <it>Y. pestis </it>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 <it>Y. pestis </it>strain KIM6+ at two physiologically relevant temperatures (26°C and 37°C).</p> <p>Results</p> <p>Differential protein display was performed for three <it>Y. pestis </it>subcellular fractions. Five characterized <it>Y. pestis </it>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 <it>E. coli</it>, was also more abundant, suggesting functional activity of Suf in <it>Y. pestis </it>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 <it>vs</it>. 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.</p> <p>Conclusions</p> <p>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 <it>Y. pestis</it>. With growth temperature as an additional variable in proteomic comparisons of the <it>Y. pestis </it>fractions (26°C and 37°C), there was little evidence for temperature-specific adaptation processes to iron starvation.</p>