MtrA is an essential regulator that coordinates antibiotic production and sporulation in<i>Streptomyces</i>species

Nf, Som; Heine, Daniel; Jt, Munnoch; Na, Holmes; Knowles, Felicity; Chandra, Govind; Seipke, Ryan F.; Pa, Hoskisson; Wilkinson, Barrie; Hutchings, Matthew I.

doi:10.1101/090399

Cited by 7 publications

(7 citation statements)

References 45 publications

(76 reference statements)

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“…The fact we could delete mtrA in a strain carrying this construct suggested that MtrA-3xFlag is functional and the strain grew like the wild-type (Supplementary Figure S2 ). We performed ChIP-seq on cultures grown for 8, 10, 12, 14, 16, 18, and 20 h in liquid MYM medium (NCBI Geo database accession number GSE84311 ; Figure 1 ; Som et al, 2016 ). Reads were mapped to the S. venezuelae NRRL B-65442 genome (GenBank accession number CP018074 ) and the chloramphenicol BGC was examined for MtrA ChIP peaks.…”

Section: Resultsmentioning

confidence: 99%

“…A preprint covering this work is available at bioRxiv: Som et al (2016). We thank David Jakeman (Dalhousie University, Canada) for an authentic jadomycin A standard.…”

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confidence: 99%

“…We thank Mark Buttner for the gift of S. venezuelae NRRL B-65442, cosmid Sv-6-A04 and helpful discussions, Matt Bush and Keith Chater for helpful discussions and critical reading of the manuscript and Elaine Patrick for excellent technical support. A preprint covering this work is available at bioRxiv: Som et al (2016) . We thank David Jakeman (Dalhousie University, Canada) for an authentic jadomycin A standard.…”

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confidence: 99%

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The Conserved Actinobacterial Two-Component System MtrAB Coordinates Chloramphenicol Production with Sporulation in Streptomyces venezuelae NRRL B-65442

et al. 2017

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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.

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Section: Resultsmentioning

confidence: 99%

“…A preprint covering this work is available at bioRxiv: Som et al (2016). We thank David Jakeman (Dalhousie University, Canada) for an authentic jadomycin A standard.…”

mentioning

confidence: 99%

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confidence: 99%

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The Conserved Actinobacterial Two-Component System MtrAB Coordinates Chloramphenicol Production with Sporulation in Streptomyces venezuelae NRRL B-65442

et al. 2017

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“…This research was supported by a BBSRC PhD studentship to N. S., a UEA-funded PhD studentship to F. K., a Medical Research Council grant G0801721 to M. I. H. and Natural Environment Research Council responsive mode grants NE/M015033/1 and NE/M014657/1 to M. I. H. and B. W. An earlier version of this work was published as a preprint on bioRxiv [ 31 ].…”

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confidence: 99%

The MtrAB two-component system controls antibiotic production in Streptomyces coelicolor A3(2)

et al. 2017

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MtrAB is a highly conserved two-component system implicated in the regulation of cell division in the Actinobacteria. It coordinates DNA replication with cell division in the unicellular Mycobacterium tuberculosis and links antibiotic production to sporulation in the filamentous Streptomyces venezuelae. Chloramphenicol biosynthesis is directly regulated by MtrA in S. venezuelae and deletion of mtrB constitutively activates MtrA and results in constitutive over-production of chloramphenicol. Here we report that in Streptomyces coelicolor, MtrA binds to sites upstream of developmental genes and the genes encoding ActII-1, ActII-4 and RedZ, which are cluster-situated regulators of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red). Consistent with this, deletion of mtrB switches on the production of Act, Red and streptorubin B, a product of the Red pathway. Thus, we propose that MtrA is a key regulator that links antibiotic production to development and can be used to upregulate antibiotic production in distantly related streptomycetes.

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“…In addition, several Streptomyces strains, such as Streptomyces hygroscopicus, Streptomyces malaysiensis, Streptomyces violaceusniger YH27A, S. coelicolor, S. violaceusniger YCED-9, and Streptomyces sp. isolate KY-33, isolated from rhizosphere soil, have been reported to be potential antifungal agents against different soil-borne plant pathogens (Cheng et al, 2010;Gherbawy et al, 2012;Wu et al, 2012;Ghadge and Patil, 2016;Som et al, 2017;Shrivastava and Kumar, 2018). The P-solubilizing Streptomyces griseus BH7 strain, isolated from Moroccan phosphate mines, was shown to inhibit the growth of potentially phytopathogenic fungi, bacteria (gram+/-) and yeasts.…”

Section: Phosphate-solubilizing Streptomyces As Biocontrol Agentsmentioning

confidence: 99%

Diversity, mechanisms and beneficial features of phosphate-solubilizing Streptomyces in sustainable agriculture: A review

2022

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Currently, the use of phosphate (P) biofertilizers among many bioformulations has attracted a large amount of interest for sustainable agriculture. By acting as growth promoters, members of the Streptomyces genus can positively interact with plants. Several studies have shown the great potential of this bacterial group in supplementing P in a soluble, plant-available form by several mechanisms. Furthermore, some P-solubilizing Streptomyces (PSS) species are known as plant growth-promoting rhizobacteria that are able to promote plant growth through other means, such as increasing the availability of soil nutrients and producing a wide range of antibiotics, phytohormones, bioactive compounds, and secondary metabolites other than antimicrobial compounds. Therefore, the use of PSS with multiple plant growth-promoting activities as an alternative strategy appears to limit the negative impacts of chemical fertilizers in agricultural practices on environmental and human health, and the potential effects of these PSS on enhancing plant fitness and crop yields have been explored. However, compared with studies on the use of other gram-positive bacteria, studies on the use of Streptomyces as P solubilizers are still lacking, and their results are unclear. Although PSS have been reported as potential bioinoculants in both greenhouse and field experiments, no PSS-based biofertilizers have been commercialized to date. In this regard, this review provides an overview mainly of the P solubilization activity of Streptomyces species, including their use as P biofertilizers in competitive agronomic practices and the mechanisms through which they release P by solubilization/mineralization, for both increasing P use efficiency in the soil and plant growth. This review further highlights and discusses the beneficial association of PSS with plants in detail with the latest developments and research to expand the knowledge concerning the use of PSS as P biofertilizers for field applications by exploiting their numerous advantages in improving crop production to meet global food demands.

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MtrA is an essential regulator that coordinates antibiotic production and sporulation inStreptomycesspecies

Cited by 7 publications

References 45 publications

The Conserved Actinobacterial Two-Component System MtrAB Coordinates Chloramphenicol Production with Sporulation in Streptomyces venezuelae NRRL B-65442

The Conserved Actinobacterial Two-Component System MtrAB Coordinates Chloramphenicol Production with Sporulation in Streptomyces venezuelae NRRL B-65442

The MtrAB two-component system controls antibiotic production in Streptomyces coelicolor A3(2)

Diversity, mechanisms and beneficial features of phosphate-solubilizing Streptomyces in sustainable agriculture: A review

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