The role of the Nitrogen Assimilation Control protein (NAC) in the responseof Klebsiella pneumoniae to nitrogen limitation.

[摘要] The nitrogen assimilation control protein of Klebsiella pneumoniae links the specialized nitrogen regulatory system that requires RNA polymerase bearing σ54 and the major form of the cellular RNA polymerase bearing σ70.NAC both activates and represses transcription.In order to activate transcription NAC requires a 15bp core consensus site of ATA-N9-TAT.This consensus site is able to function when centered at -64, -59, -47, and -44 at the characterized NAC sites.Data present in this thesis demonstrates that the mechanism of NAC transcriptional activation at these sites is flexible and that a site natively centered at -64 can function at -59 or -47 suggesting that NAC might activate transcription in a similar manner from all sites. This suggests that the NAC binding site is functionally flexible and that NAC control of a promoter might be easy to gain.The functional flexibility of NAC may allow NAC to control many promoters.Some of the data presented here demonstrates that under nitrogen limitation NAC is bound to 98 unique regions of the chromosome in K.pneumoniae.Most of these regions contain genes involved in nitrogen metabolism but some contain genes that are involved in carbon and energy acquisition or cellular growth rate control.This suggests an expanded and flexible role of NAC in the response of K.pneumoniae to nitrogen limitation.NAC might play a role in regulating other aspects of cellular physiology in addition to nitrogen metabolism in response to nitrogen limitation.In addition to the flexibility of NAC in responding to nitrogen limitation, other stress responses help fine-tune the response to nitrogen limitation.Data presented in this thesis demonstrate that the stringent response concurrently regulates at least one promoter (codBp) that is regulated by NAC in response to nitrogen limitation.In this case the regulation by the two systems is in the opposite direction, NAC activating the promoter and the stringent response repressing the promoter.The ability to fine-tune the response of metabolic genes suggests that the nitrogen stress response in K.pneumoniae is flexible in the genes it controls, how they are controlled, and the degree to which they are regulated.

[发布机构] University of Michigan

[效力级别] Nitrogen

[关键词] Metabolism;Nitrogen;Molecular;Cellular and Developmental Biology;Science;Molecular, Cellular, and Developmental Biology