Shields et al. 2024 (PRJNA706704)
General Details
| Title | Comparative Ribo-Seq of Staphylococcus aureus harboring A2058-unmodified ribosomes and m6A2058-modified ribosomes |
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| Organism | |
| Number of Samples | 10 |
| Release Date | 2021/03/04 00:00 |
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| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP309329 |
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| ENA | SRP309329 |
| GEO | |
| BioProject | PRJNA706704 |
Publication
| Title | |
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| Authors | Shields KE,Ranava D,Tan Y,Zhang D,Yap MF |
| Journal | PLoS pathogens |
| Publication Date | 2024 Jan |
| Abstract | Macrolides, lincosamides, and streptogramin B (MLS) are structurally distinct molecules that are among the safest antibiotics for prophylactic use and for the treatment of bacterial infections. The family of erythromycin resistance methyltransferases (Erm) invariantly install either one or two methyl groups onto the N6,6-adenosine of 2058 nucleotide (m6A2058) of the bacterial 23S rRNA, leading to bacterial cross-resistance to all MLS antibiotics. Despite extensive structural studies on the mechanism of Erm-mediated MLS resistance, how the m6A epitranscriptomic mark affects ribosome function and bacterial physiology is not well understood. Here, we show that Staphylococcus aureus cells harboring m6A2058 ribosomes are outcompeted by cells carrying unmodified ribosomes during infections and are severely impaired in colonization in the absence of an unmodified counterpart. The competitive advantage of m6A2058 ribosomes is manifested only upon antibiotic challenge. Using ribosome profiling (Ribo-Seq) and a dual-fluorescence reporter to measure ribosome occupancy and translational fidelity, we found that specific genes involved in host interactions, metabolism, and information processing are disproportionally deregulated in mRNA translation. This dysregulation is linked to a substantial reduction in translational capacity and fidelity in m6A2058 ribosomes. These findings point to a general 'inefficient translation' mechanism of trade-offs associated with multidrug-resistant ribosomes. Copyright: © 2024 Shields et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| PMC | PMC10833563 |
| PMID | 38252661 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR13858939 | PRJNA706704 | Staphylococcus aureus | Ribo-Seq |  |
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| SRR13858940 | PRJNA706704 | Staphylococcus aureus | RNA-Seq | |
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| SRR13858941 | PRJNA706704 | Staphylococcus aureus | Ribo-Seq | |
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| SRR13858942 | PRJNA706704 | Staphylococcus aureus | RNA-Seq | |
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| SRR13858943 | PRJNA706704 | Staphylococcus aureus | Ribo-Seq | |
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| SRR13858944 | PRJNA706704 | Staphylococcus aureus | RNA-Seq | |
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| SRR13858945 | PRJNA706704 | Staphylococcus aureus | Ribo-Seq | |
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| SRR13858946 | PRJNA706704 | Staphylococcus aureus | Ribo-Seq | |
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| SRR13858947 | PRJNA706704 | Staphylococcus aureus | RNA-Seq | |
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| SRR13858948 | PRJNA706704 | Staphylococcus aureus | RNA-Seq | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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