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Title: Studies on the global regulator BipA
Author: Hodey, Michelle Louise
ISNI:       0000 0001 3579 6449
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2007
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Microorganisms use diverse mechanisms to control the expression of their genes and many of these processes are essential for cell survival. This dissertation concerns a novel type of regulatory protein, termed BipA, which is found in many bacteria including harmless commensals such as Escherichia coli K-12, symbionts such as Sinorhizobium meliloti, and pathogens such as Salmonella and enteropathogenic and enterohaemorrhagic E. coli. BipA regulates a range of cellular processes that influence both the survival and virulence of microorganisms. In contrast to other global regulatory proteins, however, it functions as a GTPase that interacts with 70S ribosomes, suggesting that it may influence the translation of one or more target mRNA transcripts. It has previously been proposed that BipA directly regulates the translation of another global regulatory protein known as Fis. However, a phenotypic comparison bipA and tis null mutants of E. coli revealed that, while flagellamediated cell motility was impaired in both mutants, the tis mutant successfully formed colonies at temperatures below 30°C whereas the bipA null mutant did not. These observations indicate the involvement of BipA in processes that are not mediated through Fis. They also suggest that BipA is positioned higher up in the regulatory hierarchy than Fis. In addition to comparing bipA and tis phenotypes, the effects of ectopic expression of Fis were studied. Aberrant Fis expression was shown to be deleterious to cell growth, blocking cell division and hence causing filamentation in E. coli. During the course of this study results were obtained that were inconsistent with the findings presented for the control of Fis expression by BipA. Re-examination of some previously reported data indicates it is unsafe to conclude that BipA directly controls the expression of Fis. In view of these circumstances, a search for additional protein targets that are directly or indirectly regulated by BipA was initiated. Proteomic analysis of lag phase cells from a bipA null mutant of Salmonella enterica serovar Typhimurium and its parent strain uncovered candidate proteins whose expression appears to be influenced by BipA, including SipC, a component associated with the SPI-1 type three secretion system, which is important for virulence in this pathogen.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available