The Role of Periplasmic Disulfide Bond Status in the Regulation of the Salmonella SPI1 Type Three Secretion System
Lin, Dongxia
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https://hdl.handle.net/2142/72517
Description
Title
The Role of Periplasmic Disulfide Bond Status in the Regulation of the Salmonella SPI1 Type Three Secretion System
Author(s)
Lin, Dongxia
Issue Date
2009
Doctoral Committee Chair(s)
Farrand, Stephen K.
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Microbiology
Abstract
Salmonella enterica serovar Typhimurium injects a set of effector proteins into the host cell cytoplasm via the Salmonella Pathogenicity Island I (SPI1) type III secretion system (T3SS) to induce inflammatory diarrhea and bacterial uptake into intestinal epithelial cells. The master SPI1 regulatory gene hilA is controlled directly by three AraC-like regulators: HilD, HilC and RtsA. A periplasmic disulfide bond oxidoreductase DsbA is required for SPI1 T3SS function. RtsA directly activates dsbA and deletion of dsbA leads to loss of SPI1-dependent secretion. We have studied the dsbA phenotypes by monitoring expression of SPI1 regulatory, structural, and effector genes. In this work, we present evidence that loss of DsbA independently affects SPI1 regulation and SPI1 function. The dsbA-mediated feedback inhibition on SPI1 transcription is not due to defects in the SPI1 T3SS apparatus. Rather, the transcriptional response is dependent on both the flagellar protein FliZ and the RcsCDB system, which also affects fliZ transcription. Thus, the status of disulfide bonds in the periplasm affects expression of the SPI1 system indirectly via regulation of the flagellar apparatus. RcsCDB can also affect SPI1 independently of FliZ. FliZ-mediated induction of hilA expression is through HilD, while RtsA and HilC act as amplifiers of the signal. Preliminary data show that FliZ regulates HilD at the level of HilD protein. Salmonella enterica serovar Typhimurium also encodes a paralogous pair of proteins to DsbA and DsbB, DsbL and DsbI, downstream of a periplasmic arylsulfate sulfotransferase (ASST). Here we show that DsbL and DsbI function as a redox pair for disulfide bond formation and, as such, affect transcription of the SPI1 type three secretion system genes and activation of the RcsCDB system. In contrast to DsbA/DsbB, however, the DsbL/DsbI system cannot catalyze the disulfide bond formation in flagellar assembly. We further demonstrate that DsbL and DsbI are required for ASST activity in Salmonella.
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