MtrAB-LpqB: a conserved pathway regulating cell division in the phylum Actinobacteria?

Som, Nicolle (2016) MtrAB-LpqB: a conserved pathway regulating cell division in the phylum Actinobacteria? Doctoral thesis, University of East Anglia.

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Abstract

Streptomyces are ubiquitous in soil and face a rapidly changing environment. Like other bacteria, they sense and respond to external stimuli via two component systems and Streptomyces species encode a particularly high number of these systems. One of these two component systems is called MtrAB-LpqB and it is highly conserved in the phylum Actinobacteria. Previous work in Mycobacterium tuberculosis, Corynebacterium glutamicum and Streptomyces coelicolor indicates that MtrAB-LpqB is involved in osmosensing and cell cycle progression. To investigate the function of MtrAB-LpqB I attempted to make single gene deletions in the new model organism Streptomyces venezuelae. I also performed chromatin immunoprecipitation and sequencing (ChIP-seq) against MtrA-3xFlag in S. venezuelae and S. coelicolor to identify the regulon of genes under its control. I present evidence that MtrA is essential in S. venezuelae whereas MtrB is dispensable. It was not possible to confirm deletion of lpqB. Deletion of mtrB activates MtrA and leads to the overproduction of cryptic secondary metabolite biosynthetic gene clusters (BGCs). The same effect was achieved by introducing a gain of function MtrA protein into the S. venezuelae wild-type strain. The cryptic BGCs are activated because MtrA binds to target genes spanning 85% of the BGCs in S. venezuelae and S. coelicolor. In Streptomyces, antibiotic production is linked to development and the MtrA regulon overlaps with the master regulator of development, BldD. The results presented here suggest that MtrAB senses external signals and modulates target gene expression to coordinate development with the production of secondary metabolites.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Katie Miller
Date Deposited: 04 Jul 2017 15:01
Last Modified: 04 Jul 2017 15:01
URI: https://ueaeprints.uea.ac.uk/id/eprint/64007
DOI:

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