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A putative mechanism underlying secondary metabolite overproduction by Streptomyces strains with a 23S rRNA mutation conferring erythromycin resistance

  • Applied microbial and cell physiology
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Abstract

Mutations in rrn encoding ribosomal RNA (rRNA) and rRNA modification often confer resistance to ribosome-targeting antibiotics by altering the site of their interaction with the small (30S) and large (50S) subunits of the bacterial ribosome. The highly conserved central loop of domain V of 23S rRNA (nucleotides 2042–2628 in Escherichia coli; the exact position varies by species) of the 50S subunit, which is implicated in peptidyl transferase activity, is known to be important in macrolide interactions and resistance. In this study, we identified an A2302T mutation in the rrnA-23S rRNA gene and an A2281G mutation in the rrnC-23S rRNA gene that were responsible for resistance to erythromycin in the model actinomycete Streptomyces coelicolor A3(2) and its close relative Streptomyces lividans 66, respectively. Interestingly, genetic and phenotypic characterization of the erythromycin-resistant mutants indicated a possibility that under coexistence of the 23S rRNA mutation and mutations in other genes, S. coelicolor A3(2) and S. lividans 66 can produce abundant amounts of the pigmented antibiotics actinorhodin and undecylprodigiosin depending on the combinations of mutations. Herein, we report the unique phenomenon occurring by unexpected characteristics of the 23S rRNA mutations that can affect the emergence of additional mutations probably with an upswing in spontaneous mutations and enrichment in their variations in Streptomyces strains. Further, we discuss a putative mechanism underlying secondary metabolite overproduction by Streptomyces strains with a 23S rRNA mutation conferring erythromycin resistance.

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Funding

This work was financially supported by a Grant-in-Aid for Young Scientists (A) from the Japan Society for the Promotion of Science (Grant No. 25712008) and by the Hokuto Bio-science Promotion Foundation (Japan) to T. H.

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Author notes

  1. Kanata Hoshino and Yu Imai contributed equally to this work.

Authors and Affiliations

  1. Department of Biomolecular Innovation, Institute for Biomedical Sciences, Shinshu University, Nagano, 399-4598, Japan

    Kanata Hoshino, Keiichiro Mukai, Ryoko Hamauzu & Takeshi Hosaka

  2. Graduate School of Medicine, Science and Technology, Shinshu University, Nagano, 399-4598, Japan

    Kanata Hoshino & Takeshi Hosaka

  3. Antimicrobial Discovery Center, Northeastern University, Boston, MA, 02115, USA

    Yu Imai

  4. Graduate School of Science and Technology, Shinshu University, Nagano, 399-4598, Japan

    Keiichiro Mukai & Takeshi Hosaka

  5. Department of Life Science, Hiroshima Institute of Technology, Hiroshima, 731-5193, Japan

    Kozo Ochi

Authors
  1. Kanata Hoshino
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  2. Yu Imai
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Correspondence to Takeshi Hosaka.

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Hoshino, K., Imai, Y., Mukai, K. et al. A putative mechanism underlying secondary metabolite overproduction by Streptomyces strains with a 23S rRNA mutation conferring erythromycin resistance. Appl Microbiol Biotechnol 104, 2193–2203 (2020). https://doi.org/10.1007/s00253-019-10288-1

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