Som, NF, Heine, D, Holmes, NA et al. (6 more authors) (2017) The Conserved Actinobacterial Two-Component System MtrAB Coordinates Chloramphenicol Production with Sporulation in Streptomyces venezuelae NRRL B-65442. Frontiers in Microbiology, 8. 1145. ISSN 1664-302X
Abstract
Streptomyces bacteria make numerous secondary metabolites, including half of all known antibiotics. Production of antibiotics is usually coordinated with the onset of sporulation but the cross regulation of these processes is not fully understood. This is important because most Streptomyces antibiotics are produced at low levels or not at all under laboratory conditions and this makes large scale production of these compounds very challenging. Here, we characterize the highly conserved actinobacterial two-component system MtrAB in the model organism Streptomyces venezuelae and provide evidence that it coordinates production of the antibiotic chloramphenicol with sporulation. MtrAB are known to coordinate DNA replication and cell division in Mycobacterium tuberculosis where TB-MtrA is essential for viability but MtrB is dispensable. We deleted mtrB in S. venezuelae and this resulted in a global shift in the metabolome, including constitutive, higher-level production of chloramphenicol. We found that chloramphenicol is detectable in the wild-type strain, but only at very low levels and only after it has sporulated. ChIP-seq showed that MtrA binds upstream of DNA replication and cell division genes and genes required for chloramphenicol production. dnaA, dnaN, oriC, and wblE (whiB1) are DNA binding targets for MtrA in both M. tuberculosis and S. venezuelae. Intriguingly, over-expression of TB-MtrA and gain of function TB- and Sv-MtrA proteins in S. venezuelae also switched on higher-level production of chloramphenicol. Given the conservation of MtrAB, these constructs might be useful tools for manipulating antibiotic production in other filamentous actinomycetes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Som, Heine, Holmes, Munnoch, Chandra, Seipke, Hoskisson, Wilkinson and Hutchings. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms |
Keywords: | Chloramphenicol; Cell Division; mtrA; Streptomyces; antibiotics |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Jun 2017 10:14 |
Last Modified: | 14 Aug 2017 15:13 |
Status: | Published |
Publisher: | Frontiers Media |
Identification Number: | 10.3389/fmicb.2017.01145 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:117388 |