My research focuses on how iron and heme affect virulence of Pseudomonas aeruginosa, an important human pathogen that commonly plagues cancer patients, burn victims, and individuals with cystic fibrosis. In order to establish successful infection, P. aeruginosa requires iron and employs several strategies for its acquisition, including the uptake and degradation of iron-porphyrin, or heme. Although required for survival, surplus iron or heme can lead to oxidative stress. In iron-replete environments, the ferric uptake regulator (Fur) blocks expression of genes required for iron and heme uptake, as well as two nearly identical genes encoding the PrrF1 and PrrF2 small regulatory RNAs. The PrrF RNAs negatively affect the expression of a large number of genes whose products function in key metabolic pathways. Consequently, the PrrF RNAs are capable of exerting wide-ranging effects on multiple aspects of P. aeruginosa physiology and virulence.
Heme is an abundant source of iron in the human body, and its acquisition by P. aeruginosa is hypothesized to play a significant role in infection. Because of the potentially toxic effects of heme, however, it is also expected that a heme regulatory system coordinates expression of genes for heme uptake, degradation, and biosynthesis. I previously showed that the prrF locus encodes an additional, longer RNA, designated PrrH, which is repressed by heme and believed to impart additional regulatory activities to P. aeruginosa. Current studies in my laboratory are focused on: 1) determining the mechanism by which the PrrH RNA is expressed, and 2) uncovering the biological function(s) of PrrH in P. aeruginosa. Long-term goals of this research include targeting heme regulatory and uptake mechanisms for therapeutic purposes.
Oglesby-Sherrouse AG, Vasil ML. Characterization of a heme-regulated non-coding RNA encoded by the prrF locus of Pseudomonas aeruginosa. PLoS One. 2010 Apr 8;5(4):e9930.
Oglesby AG, Farrow JM 3rd, Lee JH, Tomaras AP, Greenberg EP, Pesci EC, Vasil ML. The influence of iron on Pseudomonas aeruginosa physiology: a regulatory link between iron and quorum sensing. J Biol Chem. 2008 Jun 6;283(23):15558-67. Epub 2008 Apr 18.
Payne SM, Wyckoff EE, Murphy ER, Oglesby AG, Boulette ML, Davies NM. Iron and pathogenesis of Shigella: iron acquisition in the intracellular environment. Biometals. 2006 Apr;19(2):173-80. Review.
Oglesby AG, Murphy ER, Iyer VR, Payne SM. Fur regulates acid resistance in Shigella flexneri via RyhB and ydeP. Mol Microbiol. 2005 Dec;58(5):1354-67.
Mey AR, Wyckoff EE, Oglesby AG, Rab E, Taylor RK, Payne SM. Identification of the Vibrio cholerae enterobactin receptors VctA and IrgA: IrgA is not required for virulence. Infect Immun. 2002 Jul;70(7):3419-26.
Links of Interest:Oglesby-Sherrouse Lab
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