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BipA : A new ribosome accessory protein that regulates 'Escherichia coli' virulence

BipA : A new ribosome accessory protein that regulates 'Escherichia coli' virulence
BipA : A new ribosome accessory protein that regulates 'Escherichia coli' virulence

This thesis describes the functional characterisation of BipA, a member of the ribosome-binding GTPase superfamily, that is widely distributed in bacteria and plants and that regulates the characteristic ability of EPEC to rearrange the actin cytoskeleton of infected host cells. This process involves a 35 kb cluster of genes in EPEC known as the Locus of Enterocyte Effacement (LEE) that codes for a type III secretion system and associated effector proteins. To study the role of BipA in EPEC pathogenesis, a series of mutant derivatives were produced using targeted mutation of the chromosomal bipA gene. Analysis of a bipA null mutant of EPEC strain E2248/69 showed that the synthesis of the key effector proteins EspA, EspB, EspD, Tir and intimin was blocked. Moreover, BipA also regulated the proteolytic degradation of intimin. Analysis of further mutants indicates that BipA does not operate via three known regulators of the EPEC genes involved in A/E lesion formation (Integration Host Factor, H-NS and Per). However, transcription of the ler gene, coding for a LEE-encoded regulator, was abolished in the bipA null mutant, indicating that BipA directly or indirectly controls Ler expression.

Other studies indicated that BipA regulates a range of virulence and stress processes. Although growth of EPEC at 37°C was unaffected in the bipA null mutants, BipA was required for growth at low temperatures. This finding was exploited in conjunction with a novel transposable promoter system to construct strains of E. coli in which growth at low temperature was dependent on the sugar L-arabinose. Additionally, BipA negatively regulated cell motility in EPEC. Thus BipA has all the hallmarks of a global regulator.

University of Southampton
Grant, Andrew James
805ab05b-26c3-4945-8c0a-e0247b0b8bc9
Grant, Andrew James
805ab05b-26c3-4945-8c0a-e0247b0b8bc9

Grant, Andrew James (2001) BipA : A new ribosome accessory protein that regulates 'Escherichia coli' virulence. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

This thesis describes the functional characterisation of BipA, a member of the ribosome-binding GTPase superfamily, that is widely distributed in bacteria and plants and that regulates the characteristic ability of EPEC to rearrange the actin cytoskeleton of infected host cells. This process involves a 35 kb cluster of genes in EPEC known as the Locus of Enterocyte Effacement (LEE) that codes for a type III secretion system and associated effector proteins. To study the role of BipA in EPEC pathogenesis, a series of mutant derivatives were produced using targeted mutation of the chromosomal bipA gene. Analysis of a bipA null mutant of EPEC strain E2248/69 showed that the synthesis of the key effector proteins EspA, EspB, EspD, Tir and intimin was blocked. Moreover, BipA also regulated the proteolytic degradation of intimin. Analysis of further mutants indicates that BipA does not operate via three known regulators of the EPEC genes involved in A/E lesion formation (Integration Host Factor, H-NS and Per). However, transcription of the ler gene, coding for a LEE-encoded regulator, was abolished in the bipA null mutant, indicating that BipA directly or indirectly controls Ler expression.

Other studies indicated that BipA regulates a range of virulence and stress processes. Although growth of EPEC at 37°C was unaffected in the bipA null mutants, BipA was required for growth at low temperatures. This finding was exploited in conjunction with a novel transposable promoter system to construct strains of E. coli in which growth at low temperature was dependent on the sugar L-arabinose. Additionally, BipA negatively regulated cell motility in EPEC. Thus BipA has all the hallmarks of a global regulator.

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Published date: 2001

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Local EPrints ID: 464469
URI: http://eprints.soton.ac.uk/id/eprint/464469
PURE UUID: 8375db89-c652-415f-aa51-03b468ca3f1a

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Date deposited: 04 Jul 2022 23:39
Last modified: 16 Mar 2024 19:32

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Author: Andrew James Grant

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