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Molecular basis of cycloheximide resistance in the Ophiostomatales revealed

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Abstract

Resistance to the antibiotic Cycloheximide has been reported for a number of fungal taxa. In particular, some yeasts are known to be highly resistant to this antibiotic. Early research showed that this resulted from a transition mutation in one of the 60S ribosomal protein genes. In addition to the yeasts, most genera and species in the Ophiostomatales are highly resistant to this antibiotic, which is widely used to selectively isolate these fungi. Whole-genome sequences are now available for numerous members of the Ophiostomatales providing an opportunity to determine whether the mechanism of resistance in these fungi is the same as that reported for yeast genera such as Kluyveromyces. We examined all the available genomes for the Ophiostomatales and discovered that a transition mutation in the gene coding for ribosomal protein eL42, which results in the substitution of the amino acid Proline to Glutamine, likely confers resistance to this antibiotic. This change across all genera in the Ophiostomatales suggests that the mutation arose early in the evolution of these fungi.

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Data availability

The genome data used in this study are available in the NCBI repository, https://www.ncbi.nlm.nih.gov. The accession numbers for all genomes are indicated in Table 1. The Microascus genome data is available on the JGI mycocosm website (https://mycocosm.jgi.doe.gov/mycocosm/home). The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We are grateful to the South African Department of Science and Innovation (DSI) and National Research Foundation (NRF) for financial support through the South African Research Chairs Initiative (SARChI), specifically BDW’s SARChI Chair in Fungal Genomics (UID98353). The Grant holders acknowledge that opinions, findings and conclusions or recommendations expressed in any publication generated by NRF-supported research are that of the author(s), and that the NRF accepts no liability whatsoever in this regard

Funding

This work was supported by grants from the South African National Research Foundation.

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All authors contributed to the study conception and design. The first draft of the manuscript was written by BW and all authors commented on subsequent versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Brenda D. Wingfield.

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Communicated by Michael Polymenis.

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294_2022_1235_MOESM1_ESM.jpg

Figure S1. Phylogenomic tree (left) and alignment of the ribosomal protein eL42 sequences (right) in 69 fungal species residing in the Saccharomycetes and the Sordariomycetes. The red stars indicate species that are known to be resistant to cycloheximide

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Wingfield, B.D., Wingfield, M.J. & Duong, T.A. Molecular basis of cycloheximide resistance in the Ophiostomatales revealed. Curr Genet 68, 505–514 (2022). https://doi.org/10.1007/s00294-022-01235-1

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  • DOI: https://doi.org/10.1007/s00294-022-01235-1

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