TY - JOUR TI - A systems view of haloarchaeal strategies to withstand stress from transition metals. AU - Kaur, Amardeep AU - Pan, Min AU - Meislin, Megan AU - Facciotti, Marc T. AU - El-Gewely, Raafat AU - Baliga, Nitin S. T2 - Genome research AB - Given that transition metals are essential cofactors in central biological processes, misallocation of the wrong metal ion to a metalloprotein can have resounding and often detrimental effects on diverse aspects of cellular physiology. Therefore, in an attempt to characterize unique and shared responses to chemically similar metals, we have reconstructed physiological behaviors of Halobacterium NRC-1, an archaeal halophile, in sublethal levels of Mn(II), Fe(II), Co(II), Ni(II), Cu(II), and Zn(II). Over 20% of all genes responded transiently within minutes of exposure to Fe(II), perhaps reflecting immediate large-scale physiological adjustments to maintain homeostasis. At steady state, each transition metal induced growth arrest, attempts to minimize oxidative stress, toxic ion scavenging, increased protein turnover and DNA repair, and modulation of active ion transport. While several of these constitute generalized stress responses, up-regulation of active efflux of Co(II), Ni(II), Cu(II), and Zn(II), down-regulation of Mn(II) uptake and up-regulation of Fe(II) chelation, confer resistance to the respective metals. We have synthesized all of these discoveries into a unified systems-level model to provide an integrated perspective of responses to six transition metals with emphasis on experimentally verified regulatory mechanisms. Finally, through comparisons across global transcriptional responses to different metals, we provide insights into putative in vivo metal selectivity of metalloregulatory proteins and demonstrate that a systems approach can help rapidly unravel novel metabolic potential and regulatory programs of poorly studied organisms. DA - 2006/07//undefined PY - 2006 DO - 10.1101/gr.5189606 VL - 16 IS - 7 SP - 841 EP - 854 J2 - Genome Res LA - eng SN - 1088-9051 1088-9051 KW - *Models, Genetic KW - Adenosine Triphosphatases/genetics/metabolism KW - Bacterial Proteins/genetics/metabolism KW - Biological Transport, Active KW - Dose-Response Relationship, Drug KW - Gene Deletion KW - Gene Expression Regulation, Bacterial/*drug effects KW - Genes, Bacterial KW - Halobacterium/drug effects/genetics/*physiology KW - Metals, Heavy/*toxicity KW - Oligonucleotide Array Sequence Analysis KW - RNA, Messenger/metabolism KW - Time Factors KW - Transcription, Genetic KW - Transition Elements/chemistry/*toxicity ER -