Expression Patterns, Genomic Conservation and Input Into Developmental Regulation of the GGDEF/EAL/HD-GYP Domain Proteins in Streptomyces.

Mahmoud M. Al-Bassam,Sandra Lindenberg,Sara Alina Neumann,Natalia Tschowri,Julian Haist

doi:10.3389/fmicb.2018.02524

Mahmoud M. Al-Bassam, Sandra Lindenberg + Show 3 more

Open Access

https://doi.org/10.3389/fmicb.2018.02524

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Abstract

To proliferate, antibiotic-producing Streptomyces undergo a complex developmental transition from vegetative growth to the production of aerial hyphae and spores. This morphological switch is controlled by the signaling molecule cyclic bis-(3′,5′) di-guanosine-mono-phosphate (c-di-GMP) that binds to the master developmental regulator, BldD, leading to repression of key sporulation genes during vegetative growth. However, a systematical analysis of all the GGDEF/EAL/HD-GYP proteins that control c-di-GMP levels in Streptomyces is still lacking. Here, we have FLAG-tagged all 10 c-di-GMP turnover proteins in Streptomyces venezuelae and characterized their expression patterns throughout the life cycle, revealing that the diguanylate cyclase (DGC) CdgB and the phosphodiesterase (PDE) RmdB are the most abundant GGDEF/EAL proteins. Moreover, we have deleted all the genes coding for c-di-GMP turnover enzymes individually and analyzed morphogenesis of the mutants in macrocolonies. We show that the composite GGDEF-EAL protein CdgC is an active DGC and that deletion of the DGCs cdgB and cdgC enhance sporulation whereas deletion of the PDEs rmdA and rmdB delay development in S. venezuelae. By comparing the pan genome of 93 fully sequenced Streptomyces species we show that the DGCs CdgA, CdgB, and CdgC, and the PDE RmdB represent the most conserved c-di-GMP-signaling proteins in the genus Streptomyces.

Highlights

Streptomyces are high G + C Gram-positive Actinobacteria with a great interest for medicine and industry, representing the most abundant natural source of antibiotics and other medically relevant secondary metabolites
Streptomyces venezuelae has 10 chromosomally encoded and one plasmid-encoded protein involved in c-di-GMP metabolism (Table 1)
In the genus Streptomyces, the conserved master regulator BldD acts as a central hub that integrates c-di-GMP signals into the developmental program

Summary

Introduction

Streptomyces are high G + C Gram-positive Actinobacteria with a great interest for medicine and industry, representing the most abundant natural source of antibiotics and other medically relevant secondary metabolites. Streptomyces grow by extension of their hyphal tips and by initiating new lateral branches. It is due to this mode of growth that vegetative-phase colonies consist of tightly interwoven hyphae leading to a compact mycelium that appears bald and shiny on solid medium. Reproductive aerial hyphae are formed on the surface, which differentiate into long chains of pre-spore compartments and result in a fuzzy and white appearance of the colony. At the end of the life cycle, these compartments mature into pigmented spores that give Streptomyces colonies a characteristic color. Bld regulators control the switch from the vegetative to aerial hyphae and Whi regulators are required for the transition from aerial hyphal growth to sporulation (Flärdh and Buttner, 2009; McCormick and Flärdh, 2012)

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