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Zinc depletion induces ribosome hibernation in mycobacteria.

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Li Y, Sharma MR, Koripella RK, Yang Y, Kaushal PS, Lin Q, Wade JT, Gray TA, Derbyshire KM, Agrawal RK, Ojha AK
OpenAccess logo Proc Natl Acad Sci U S A 115 8191-8196 (2018)
Related entries: 6dzi, 6dzp

Cited: 46 times
EuropePMC logo PMID: 30038002

Abstract

Bacteria respond to zinc starvation by replacing ribosomal proteins that have the zinc-binding CXXC motif (C+) with their zinc-free (C-) paralogues. Consequences of this process beyond zinc homeostasis are unknown. Here, we show that the C- ribosome in Mycobacterium smegmatis is the exclusive target of a bacterial protein Y homolog, referred to as mycobacterial-specific protein Y (MPY), which binds to the decoding region of the 30S subunit, thereby inactivating the ribosome. MPY binding is dependent on another mycobacterial protein, MPY recruitment factor (MRF), which is induced on zinc depletion, and interacts with C- ribosomes. MPY binding confers structural stability to C- ribosomes, promoting survival of growth-arrested cells under zinc-limiting conditions. Binding of MPY also has direct influence on the dynamics of aminoglycoside-binding pockets of the C- ribosome to inhibit binding of these antibiotics. Together, our data suggest that zinc limitation leads to ribosome hibernation and aminoglycoside resistance in mycobacteria. Furthermore, our observation of the expression of the proteins of C- ribosomes in Mycobacterium tuberculosis in a mouse model of infection suggests that ribosome hibernation could be relevant in our understanding of persistence and drug tolerance of the pathogen encountered during chemotherapy of TB.

Reviews - 6dzk mentioned but not cited (1)

  1. Recent Insights into the Structure and Function of Mycobacterial Membrane Proteins Facilitated by Cryo-EM. Bendre AD, Peters PJ, Kumar J. J Membr Biol 254 321-341 (2021)

Articles - 6dzk mentioned but not cited (3)

  1. Zinc depletion induces ribosome hibernation in mycobacteria. Li Y, Sharma MR, Koripella RK, Yang Y, Kaushal PS, Lin Q, Wade JT, Gray TA, Derbyshire KM, Agrawal RK, Ojha AK. Proc Natl Acad Sci U S A 115 8191-8196 (2018)
  2. Cryo- EM structure of the mycobacterial 70S ribosome in complex with ribosome hibernation promotion factor RafH. Kumar N, Sharma S, Kaushal PS. Nat Commun 15 638 (2024)
  3. research-article The small mycobacterial ribosomal protein, bS22, modulates aminoglycoside accessibility to its 16S rRNA helix-44 binding site. Majumdar S, Deep A, Sharma MR, Canestrari J, Stone M, Smith C, Koripella RK, Keshavan P, Banavali NK, Wade JT, Gray TA, Derbyshire KM, Agrawal RK. bioRxiv 2023.03.31.535098 (2023)


Reviews citing this publication (10)

  1. Ribosome Hibernation. Prossliner T, Skovbo Winther K, Sørensen MA, Gerdes K. Annu Rev Genet 52 321-348 (2018)
  2. Tolerance and Persistence to Drugs: A Main Challenge in the Fight Against Mycobacterium tuberculosis. Boldrin F, Provvedi R, Cioetto Mazzabò L, Segafreddo G, Manganelli R. Front Microbiol 11 1924 (2020)
  3. Multi-metal nutrient restriction and crosstalk in metallostasis systems in microbial pathogens. Jordan MR, Wang J, Capdevila DA, Giedroc DP. Curr Opin Microbiol 55 17-25 (2020)
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  5. Critical Review: Propensity of Premise Plumbing Pipe Materials to Enhance or Diminish Growth of Legionella and Other Opportunistic Pathogens. Cullom AC, Martin RL, Song Y, Williams K, Williams A, Pruden A, Edwards MA. Pathogens 9 E957 (2020)
  6. Stress response as implemented by hibernating ribosomes: a structural overview. Matzov D, Bashan A, Yap MF, Yonath A. FEBS J 286 3558-3565 (2019)
  7. Interchangeable utilization of metals: New perspectives on the impacts of metal ions employed in ancient and extant biomolecules. Smethurst DGJ, Shcherbik N. J Biol Chem 297 101374 (2021)
  8. Ribosome hibernation: a new molecular framework for targeting nonreplicating persisters of mycobacteria. Li Y, Sharma MR, Koripella RK, Banavali NK, Agrawal RK, Ojha AK. Microbiology (Reading) 167 (2021)
  9. Failure to Guard: Mitochondrial Protein Quality Control in Cancer. Friedlander JE, Shen N, Zeng A, Korm S, Feng H. Int J Mol Sci 22 8306 (2021)
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Articles citing this publication (32)

  1. Selective translation by alternative bacterial ribosomes. Chen YX, Xu ZY, Ge X, Sanyal S, Lu ZJ, Javid B. Proc Natl Acad Sci U S A 117 19487-19496 (2020)
  2. Hibernation factors directly block ribonucleases from entering the ribosome in response to starvation. Prossliner T, Gerdes K, Sørensen MA, Sørensen MA, Winther KS. Nucleic Acids Res 49 2226-2239 (2021)
  3. Progression from remodeling to hibernation of ribosomes in zinc-starved mycobacteria. Li Y, Corro JH, Palmer CD, Ojha AK. Proc Natl Acad Sci U S A 117 19528-19537 (2020)
  4. Conditional DnaB Protein Splicing Is Reversibly Inhibited by Zinc in Mycobacteria. Woods D, Vangaveti S, Egbanum I, Sweeney AM, Li Z, Bacot-Davis V, LeSassier DS, Stanger M, Hardison GE, Li H, Belfort M, Lennon CW. mBio 11 e01403-20 (2020)
  5. Hibernation-Promoting Factor Sequesters Staphylococcus aureus Ribosomes to Antagonize RNase R-Mediated Nucleolytic Degradation. Lipońska A, Yap MF. mBio 12 e0033421 (2021)
  6. COG0523 proteins: a functionally diverse family of transition metal-regulated G3E P-loop GTP hydrolases from bacteria to man. Edmonds KA, Jordan MR, Giedroc DP. Metallomics 13 mfab046 (2021)
  7. One-carbon metabolism, folate, zinc and translation. Danchin A, Sekowska A, You C. Microb Biotechnol 13 899-925 (2020)
  8. Sleeping ribosomes: Bacterial signaling triggers RaiA mediated persistence to aminoglycosides. Lang M, Krin E, Korlowski C, Sismeiro O, Varet H, Coppée JY, Mazel D, Baharoglu Z. iScience 24 103128 (2021)
  9. The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus. Basu A, Shields KE, Yap MF. J Biol Chem 295 6053-6063 (2020)
  10. Critical Role of Zur and SmtB in Zinc Homeostasis of Mycobacterium smegmatis. Goethe E, Laarmann K, Lührs J, Jarek M, Meens J, Lewin A, Goethe R. mSystems 5 e00880-19 (2020)
  11. Phenotypic effects of paralogous ribosomal proteins bL31A and bL31B in E. coli. Lilleorg S, Reier K, Volõnkin P, Remme J, Liiv A. Sci Rep 10 11682 (2020)
  12. Population genomics provides insights into the evolution and adaptation to humans of the waterborne pathogen Mycobacterium kansasii. Luo T, Xu P, Zhang Y, Porter JL, Ghanem M, Liu Q, Jiang Y, Li J, Miao Q, Hu B, Howden BP, Fyfe JAM, Globan M, He W, He P, Wang Y, Liu H, Takiff HE, Zhao Y, Chen X, Pan Q, Behr MA, Stinear TP, Gao Q. Nat Commun 12 2491 (2021)
  13. Kupyaphores are zinc homeostatic metallophores required for colonization of Mycobacterium tuberculosis. Mehdiratta K, Singh S, Sharma S, Bhosale RS, Choudhury R, Masal DP, Manocha A, Dhamale BD, Khan N, Asokachandran V, Sharma P, Ikeh M, Brown AC, Parish T, Ojha AK, Michael JS, Faruq M, Medigeshi GR, Mohanty D, Reddy DS, Natarajan VT, Kamat SS, Gokhale RS. Proc Natl Acad Sci U S A 119 e2110293119 (2022)
  14. Letter Zinc depletion does not necessarily induce ribosome hibernation in mycobacteria. Tobiasson V, Dow A, Prisic S, Amunts A. Proc Natl Acad Sci U S A 116 2395-2397 (2019)
  15. Functional Characterization of the Pseudomonas aeruginosa Ribosome Hibernation-Promoting Factor. Franklin MJ, Sandvik E, Yanardag S, Williamson KS. J Bacteriol 202 e00280-20 (2020)
  16. Letter Reply to Tobiasson et al.: Zinc depletion is a specific signal for induction of ribosome hibernation in mycobacteria. Li Y, Sharma MR, Koripella RK, Wade JT, Gray TA, Derbyshire KM, Agrawal RK, Ojha AK. Proc Natl Acad Sci U S A 116 2398-2399 (2019)
  17. Characterization of the metalloproteome of Pseudoalteromonas (BB2-AT2): biogeochemical underpinnings for zinc, manganese, cobalt, and nickel cycling in a ubiquitous marine heterotroph. Mazzotta MG, McIlvin MR, Moran DM, Wang DT, Bidle KD, Lamborg CH, Saito MA. Metallomics 13 mfab060 (2021)
  18. Replacement of S14 Protein in Ribosomes of Zinc-Starved Mycobacteria Reduces Spectinamide Sensitivity. Li Y, Koripella RK, Sharma MR, Lee RE, Agrawal RK, Ojha AK. Antimicrob Agents Chemother 65 e01833-20 (2021)
  19. Ribosomes lacking bS21 gain function to regulate protein synthesis in Flavobacterium johnsoniae. McNutt ZA, Roy B, Gemler BT, Shatoff EA, Moon KM, Foster LJ, Bundschuh R, Fredrick K. Nucleic Acids Res 51 1927-1942 (2023)
  20. Molecular Characterization and the Essential Biological Function of the Metal Chaperone Protein MtmA in Aspergillus fumigatus. Zhai P, Ma Y, Xu H, Lu L. Appl Environ Microbiol 88 e0018222 (2022)
  21. Starvation sensing by mycobacterial RelA/SpoT homologue through constitutive surveillance of translation. Li Y, Majumdar S, Treen R, Sharma MR, Corro J, Gamper HB, Manjari SR, Prusa J, Banavali NK, Stallings CL, Hou YM, Agrawal RK, Ojha AK. Proc Natl Acad Sci U S A 120 e2302006120 (2023)
  22. Zinc-Responsive Regulator Zur Regulates Zinc Homeostasis, Secondary Metabolism, and Morphological Differentiation in Streptomyces avermitilis. Lyu M, Cheng Y, Dai Y, Wen Y, Song Y, Li J, Chen Z. Appl Environ Microbiol 88 e0027822 (2022)
  23. A Novel Zinc Exporter CtpG Enhances Resistance to Zinc Toxicity and Survival in Mycobacterium bovis. Chen L, Li X, Xu P, He ZG. Microbiol Spectr 10 e0145621 (2022)
  24. Bidirectional sequestration between a bacterial hibernation factor and a glutamate metabolizing protein. Ranava D, Scheidler CM, Pfanzelt M, Fiedler M, Sieber SA, Schneider S, Yap MF. Proc Natl Acad Sci U S A 119 e2207257119 (2022)
  25. CryoEM reveals that ribosomes in microsporidian spores are locked in a dimeric hibernating state. McLaren M, Conners R, Isupov MN, Gil-Díez P, Gambelli L, Gold VAM, Walter A, Connell SR, Williams B, Daum B. Nat Microbiol 8 1834-1845 (2023)
  26. HflX is a GTPase that controls hypoxia-induced replication arrest in slow-growing mycobacteria. Ngan JYG, Pasunooti S, Tse W, Meng W, Ngan SFC, Jia H, Lin JQ, Ng SW, Jaafa MT, Cho SLS, Lim J, Koh HQV, Abdul Ghani N, Pethe K, Sze SK, Lescar J, Alonso S. Proc Natl Acad Sci U S A 118 e2006717118 (2021)
  27. Multi-Omics Profiling Specifies Involvement of Alternative Ribosomal Proteins in Response to Zinc Limitation in Mycobacterium smegmatis. Dow A, Burger A, Marcantonio E, Prisic S. Front Microbiol 13 811774 (2022)
  28. Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism. Lomakin IB, Devarkar SC, Patel S, Grada A, Bunick CG. Nucleic Acids Res 51 2915-2930 (2023)
  29. Dynamic Transcriptional Landscape of Mycobacterium smegmatis under Cold Stress. Grigorov AS, Skvortsova YV, Bychenko OS, Aseev LV, Koledinskaya LS, Boni IV, Azhikina TL. Int J Mol Sci 24 12706 (2023)
  30. Inducible knockdown of Mycobacterium smegmatis MSMEG_2975 (glyoxalase II) affected bacterial growth, antibiotic susceptibility, biofilm, and transcriptome. Haris M, Chen C, Wu J, Ramzan MN, Taj A, Sha S, Ullah H, Ma Y. Arch Microbiol 204 97 (2021)
  31. Purification of Hibernating and Active C- Ribosomes from Zinc-Starved Mycobacteria. Li Y, Keshavan P, Corro JH, Koripella RK, Agrawal RK, Ojha AK. Methods Mol Biol 2314 151-166 (2021)
  32. The structure of a hibernating ribosome in a Lyme disease pathogen. Sharma MR, Manjari SR, Agrawal EK, Keshavan P, Koripella RK, Majumdar S, Marcinkiewicz AL, Lin YP, Agrawal RK, Banavali NK. Nat Commun 14 6961 (2023)


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