The Role of BldB in the Development of the Antibiotic-producing Bacteria Streptomyces

Avramova, Marieta (2021) The Role of BldB in the Development of the Antibiotic-producing Bacteria Streptomyces. Doctoral thesis, University of East Anglia.

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Abstract

The classical life cycle of Streptomyces is intricate, involving the generation of distinct developmental structures in response to environmental cues - the vegetative mycelium, the hydrophobic aerial hyphae, and mature spores. The production of clinically useful antibiotics is tightly coordinated with this complex life cycle.
Two families of developmental regulators control the life cycle transitions in Streptomyces. Bld regulators control the formation of the reproductive aerial hyphae, while Whi regulators control the differentiation of the reproductive structures into spores. This work focuses on BldB, whose function was a mystery. BldB has ten paralogues in Streptomyces venezuelae, all of which are encoded next to paralogues of the DNA-binding regulator WhiJ. Five of these BldB paralogues are encoded next to paralogues of the putative anti-sigma factor AbaA.
In this work I show that the deletion of bldB in S. venezuelae leads to a classical “bald” phenotype – the mutant cannot differentiate past vegetative growth. By screening a bacterial-two-hybrid library, I demonstrate that BldB strongly interacts with seven of its S. venezuelae BldB paralogues. The deletion of two of these paralogues results in sporulation-deficient phenotypes in S. venezuelae. RNA-seq showed a striking upregulation of all five abaA paralogues and the novel inhibitor of sporulation iosA in the ΔbldB mutant, suggesting that BldB indirectly represses the expression of these genes. I show that the tandem overexpression of abaA6 and iosA recapitulates the ΔbldB mutant phenotype. The putative anti-sigma factor AbaA6 is involved in a network of protein interactions reminiscent of SigB-like partner-switching systems. I demonstrate that one of he WhiJ paralogues, WhiJ9, directly activates the expression of iosA by binding to direct repeats in the iosA-whiJ9 intergenic region. Finally, I present evidence that BldB9 might be the protein that provides the biochemical link between BldB- and WhiJ9-mediated control of iosA expression.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Jackie Webb
Date Deposited:	28 Apr 2022 14:16
Last Modified:	28 Apr 2022 14:16
URI:	https://ueaeprints.uea.ac.uk/id/eprint/84835
DOI:

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