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Role of the CtrA cell cycle regulator in the bloodborne bacterial pathogen, Bartonella quintana.

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thesis
posted on 2021-12-07, 06:46 authored by Thomson, Robert Haydn

Bartonella quintana is an important re-emerging human pathogen and the causative agent of trench fever. It utilizes a stealth invasion strategy to infect hosts and is transmitted by lice. Throughout infection it is crucial for the bacteria to maintain a tight regulation of cell division, to prevent immune detection and allow for transmission to new hosts. CtrA is an essential master cell cycle regulatory protein found in the alpha-proteobacteria. It regulates many genes, ensuring the appropriate timing of gene expression and DNA replication. In the model organism Caulobacter crescentus, it regulates 26% of cell cycle-regulated genes. CtrA has been reported to bind two specific DNA motifs in gene promoter regions, TTAAN7TTAAC, and TTAACCAT. Genes regulated by CtrA encode proteins with a wide range of activities, including initiation of DNA replication, cell division, DNA methylation, polar morphogenesis, flagellar biosynthesis, and cell wall metabolism. However, the role of the CtrA homologue in Bartonella spp. has not been investigated. In this project we aimed to make an initial characterisation of the master cell cycle regulator CtrA. This was done by identifying gene regulatory regions containing putative CtrA binding sites and testing for direct interactions via a -galactosidase assay. It was found B. quintana CtrA shared 81 % amino acid identity with its C. crescentus homologue. Within the genome of B. quintana str. Toulouse we discovered 21 genes containing putative CtrA binding sites in their regulatory regions. Of these genes we demonstrated interactions between CtrA and the promoter region of ftsE a cell division gene [1], hemS, and hbpC, two heme regulatory genes. We also found no evidence of CtrA regulating its own expression, which was unexpected because CtrA autoregulation has been demonstrated in C. crescentus.

History

Copyright Date

2018-01-01

Date of Award

2018-01-01

Publisher

Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

Degree Discipline

Genetics

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level

Masters

Degree Name

Master of Science

Victoria University of Wellington Unit

Centre for Biodiscovery

ANZSRC Type Of Activity code

1 PURE BASIC RESEARCH

Victoria University of Wellington Item Type

Awarded Research Masters Thesis

Language

en_NZ

Victoria University of Wellington School

School of Biological Sciences

Advisors

MacKichan, Joanna